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 OJVM  Vol.11 No.1 , January 2021
Hepato-Preventive Effects of Hydroethanolic Leaves Extract of Persea americana Mill. (Lauraceae) “Avocado” against Antouka Super®Induced Damage in Male Japanese Quail (Coturnix coturnix Japonica)
Abstract: The present study was undertaken to evaluate the protective effects of Hydroethanolic leaves extract of Persea americana (HEPA) against Antouka Super?(AS) induced hepatotoxicity in male Japanese quail. In total, 40 immature male Japanese quails aged 28 days were used and divided equally into 5 groups. The groups were designed as the control group (received only a 10 ml/kg of distilled water) and the AS group (75 mg/kg b.w). Other three groups received AS (75 mg of AS/kg b.w) plus HEPA (50, 100, and 200 mg/kg b.w/day respectively) by the oral route. After 60 days of the experiment, the crushed liver was performed to obtain homogenate. The protective effects of HEPA on the biochemical parameters, oxidative stress biomarkers and histology changes in the liver were evaluated. The results indicated that AS treatment caused significant alterations in the clinical signs and behavior. It induces the increase in the content of Urea, Creatinine, Protein, AST and ALT in liver tissues and serum. The activities of enzymatic oxidative stress markers such as Superoxide Dismutase (SOD); Catalase (CAT) and Total Peroxidase (POD) also showed significant perturbations in AS-treated quails. Histopathological examination of the liver of AS-treated quails revealed liver lesions characterized by moderate to severe degenerative changes showing a number of hepatocytes undergo fatty changes, focal aggregation of the lymphocytes, multiple necrotic changes and inflammatory infiltrate. The administration of HEPA however, markedly ameliorated the toxicity of AS by protecting the levels of aforesaid biomarkers to near normal levels. These results suggested that HEPA due to its phytochemical constituents with antioxidant properties possesses significant effects against AS-induced toxicity. However, these effects were more pronounced at a dose of 200 mg/kg bw.

1. Introduction

Pesticides have been applied in agriculture and household to protect plants, animals and humans from insects and vector diseases. The negligent and random uses of pesticides can cause environmental damage, food, water contamination, and health problems (e.g. cancer, nerve disease, birth defects). Animals and humans are potentially exposed to pesticides either directly through occupational exposure or indirectly via food and water consumption Ngoumtsop et al. [1], [2].

Antouka Super® (AS) is a broad-spectrum insecticide widely used in agriculture and crop’s storage in many countries including Cameroon. It is made up of two insecticides: (Pirimiphos-methyl 16% and Permethrin 3%). Pirimiphos-methyl is a broad-spectrum organophosphate insecticide that accumulated in adipose tissue, brain and liver and has hepatotoxic potential in rat [3] [4]. Permethrin, is a pyrethroid insecticide class; due to their lipophilicity, it is a favor absorption through the gastrointestinal and confer preferential distribution into lipid-rich internal tissues, including body fat, skin, liver and kidney [5]. Hallenbeck et al. [6] reported that exposure to permethrin causes enlargement of the liver.

In fact, one possible mechanism by AS-induced toxicity is the production of reactive oxygen species (ROS) in the cell. The imbalance between ROS synthesis and the amounts of antioxidants causes oxidative stress. The presence of oxidative stress damages lipids, proteins and DNA [7] [8]. It has been reported that ROS were involved in the toxicity of organophosphate insecticides (OPIs) [9] and pyrethroid insecticides [7] [10]. Also, a positive correlation with the liver damage has been reported. ROS, especially superoxide anion and hydrogen peroxide, are important signaling molecules in developing and proliferating cells, but also in the induction of programmed cell death [11] [12]. ROS are transient species due to their high chemical reactivity that leads to the LPO and a massive protein oxidation and degradation [13] [14]. These authors reported that ROS cause DNA damage and strand breaks as a result of modifying purines and pyrimidines bases by superoxide anion radical (O2•), hydrogen peroxide (H2O2), and hydroxyl radical (HO).

The Perseaamericana Mill. tree belongs to the family Lauraceae, genus Persea and is a plant native of Central America. Apart from its use as food, the avocado is traditionally utilized for various medicinal purposes including anti-inflammatory [15]; and anti-aging agents [16], and is applied for the treatment of ulcers and cardiovascular diseases [17] [18] [19].

Previous investigations of the skin, leaves and seed revealed a predominance of compounds belonging to the group of flavonoids, proanthocyanidins, and hydrocinnamic acids [19]. Phenolics and flavonoids are bioactive compounds that have been related with a decrement of different deteriorative processes in the human body owing to their ability to reduce the formation and to scavange free radicals [20]. Rodríguez-Carpena et al. [21] ascribed the high antioxidant activity exhibited by avocado extracts in various in vitro assays to these phenolic compounds. Ekor et al. [22] and Owolabi et al. [23] reported the protective effect of P.americana against toxicity. In addition, phytochemical screening of the leaf extract of P.americana revealed the presence of flavonoids which are playing an essential role in neutralizing free radical, quenching singlet and triplet oxygen, decomposing peroxides, stabilizing lipid peroxidation and protecting the cells against oxidative damage [24] [25] [26] by donating a hydrogen atom or electron to stabilize the radical species [27].

Currently, some synthetic antioxidant use to prevent free radical damage can induce side effects Conwell et al. [28]. So, the dietary intake of natural products is considered very important for preventing a wide variety of diseases such as allergies, cardiovascular disease, certain forms of cancer, hepatic diseases, and inflammation, which involve free radical-mediated damage in pathologically generating processes [29]. Therefore, that is an essential research about suitable herbal drugs that could replace the chemical ones Owolobi et al. [30]. However, the widespread use of Perseaamericana in traditional medicine stimulated us to explore its potential biological activity. To the best of our knowledge, no previous study of the antioxidant and protective activities of hydroethanolic leaves extract of Perseaamericana (HEPA) have been reported. Therefore, the current study was designed to evaluate the antioxidant activity and protective effect of HEPA leaves against AS induced biochemical parameters, oxidative stress biomarkers and histology changes in the liver damage in male Japanese quail.

2. Materials and Methods

2.1. Birds

Forty healthy male Japanese quails aged 28 days and weighing 112 - 118 g were used in this study. Birds were housed in specialized wire cages, eight per cage, in a centralized birds care facility maintained at 22˚C - 25˚C with a relative humidity of 76% ± 5%, for 8 weeks. Animals were kept in a 12 h light-dark cycle and provided ad libitum with water and a specific diet.

2.2. Origin of Pesticide

Antouka Super® (SYNGENTA, United Kingdom) is a combined insecticide whose active principles are:

· pirimiphos-methyl (0,2-diethylamino-6-methylpirimidin-4-yl O,O-dimethyl phosphorothioate) concentrated at 19 g/kg,

· permethrin (1RS, 3RS; 1RS, 3SR)-3-(2,2-Dichlorovinyl)-2,2-dimethylcyclo- propane-1-carboxylate (3-phenoxyphenyl)) concentrated at 3 g/kg.

2.3. Plant Harvesting and Extract

Perseaamericana leaves were from Dschang, West Region of Cameroon and authenticated atthe Cameroon National Herbarium under the voucher number 18,604/Sfr/Cam. They were shade-dried, ground to obtain fine powder which was macerated in the ethanol (70˚) for 72 hrs. After filtration, the filtrate was concentrated under vacuum to remove ethanol and further dried using freezer dryer to obtain a fine powder.

2.4. Phytochemical Screening of HEPA

The phytochemical screening of the HEPA was done as described by Tiendrebeogo et al. [31] and revealed the presence of tannins, anthraquinones, phenols, alkaloids, sterols and flavonoids.

2.5. Ethical Consideration

Experimental protocols used in this study were approved by the ethical committee of the Department of Animal Science of the University of Dschang (ECDAS-UDs 23/02/2015/UDs/FASA/DSAES) and was in conformity with the internationally accepted standard ethical guidelines for laboratory animal use and care as described in the European Community guidelines; EEC Directive 86/609/EEC, of the 24th November 1986 [32].

2.6. Experimental Design

In total, 40 immature male Japanese quails aged 28 days were used and divided equally into 5 groups. The groups were designed as the control group (received only a 10 ml/kg of distilled water) and the AS group (75 mg /kg b.w) by the oral route. Other three groups received AS (75 mg of AS/kg b.w) plus HEPA (50, 100, and 200 mg/kg b.w/day respectively) by the oral route. After 60 days of the experiment, the crushed liver was performed to obtain homogenate. The doses of AS used in the study were selected from a pilot study and represent 1/15 of LD50 value obtained in quails (1125 mg/kg b.w) (personal communication). During the treatment, body weight was measured weekly.

Clinical signs and behavioral alterations: As stated in previous reports, the salient features of pirimiphos-methyl toxicity include neurotoxicity [33]. Therefore, for the present study, signs suggesting nervous disturbances (depression, decreased attraction towards feed, weakness, anorexia and dizziness) were taken into account and subjectively evaluated daily directly after administration of AS. Depending on the severity and frequency, each clinical sign was scored from 0 to +4 (0 = none, +1 = very weak, +2 = weak, +3 = moderately and +4 = severely).

2.7. Blood and Organ Collections

At the end of the treatments (8 weeks), blood was collected after sectioning the jugular vein of each bird. Serum was prepared and stored at −20˚C for subsequent analysis. After scarification of the quail by decapitation, liver was carefully removed, freed of adipose tissue, blotted dry and weighed separately. The fragment liver of each bird was then homogenized at 15% (weight/volume) of cold 0.9% NaCl followed by a centrifugation (3000 rpm, 30 min) and aliquots of supernatant were kept at −20˚C for biochemical analysis (Tchoffo et al. [34] ).

2.8. Biochemical Analysis

All biochemical measurements (total proteins in the liver, total protein in the serum, cholesterol, AST, ALT, Urea and Creatinine) were determined using CHRONOLAB kit following the manufacturer’s protocol. The levels of SOD and MDA and the activities of CAT and POD were assessed in liver homogenates using a spectrophotometer (GENESYS 20.0) and according to the methods described respectively by: [35] [36] [37] and [38].

2.9. Tissue Preparation and Histopathology

The same lobe of liver samples randomly selected from each treatment was fixed in Bouin’s fluid for 1 week, embedded in paraffin, cut at 5 µm and stained with Harris haematoxylin and eosin. The tissue sections were observed under a light microscope (Leica DM 750, ×10 and ×40) for morphology and cellular integrity.

2.10. Statistical Analysis

Differences between groups were assessed using one-way ANOVA followed by Duncan post hoc test with the significance level set at 0.05. A value of p ≤ 0.05 was considered statistically significant. Statistical analyses were performed with the aid of SPSS for Windows software program (Release 21.0) and results expressed as mean ± standard deviation.

3. Results

3.1. Clinical Signs and Behavioural Alterations

The comparison of the clinical signs, subjectively evaluated is presented in Table 1. No clinical signs and behavioural changes were observed in animals of group 1 (0 mg AS/kg bw) and group 5 (75 mg AS/kg bw + 200 mg HEPA/kg bw). Depression, decreased attraction towards feed, weakness, anorexia, diarrhea and dizziness started at the 5th week in group 2 (75 mg AS/kg bw) and 3 (75 mg AS/kg bw + 50 mg HEPA/kg bw). In addition at the 8th week, in group 2 (75 mg AS/kg bw), all the birds showed a degree of depression, decreased attraction towards food, weakness and anorexia week, while in group 3 (75 mg AS/kg bw + 50 mg HEPA/kg bw), half the birds (4/8) showed a mild degree of depression, decreased attraction towards food, weakness and anorexia.

3.2. Growth Parameters

The final body weight and body weight gain decreased (p < 0.05) in a dose-dependent manner. The opposite trend was recorded for the relative liver weight (Table 2). In the reference to the positive control (G2), the final body weight, body weight gain show significant (p < 0.05) increase in quails co-exposed to 75 mg of AS/kg bw and HEPA whatever the dose. Inversely, the relative weight of the liver decreased significantly significant (p < 0.05).

Table 1. Effects of different levels of HEPA on some qualitative clinical signs and behavioral of male Japanese quail.

Score from 0 to +4 denotes the severity of clinical signs (0: none, +1: very weak, +2: weak, +3: moderately and +4: severely);. n: number of animal; Group 1:10 ml/kg of distilled water only negative control group; Group 2: intoxicated birds receiving 75 mg of AS/kg b.w only positive control group; Group 3: intoxicated birds treated with 50 mg/kg b.w of HEPA; Group 4: intoxicated birds treated with 100 mg/kg b.w of HEPA; Group 5: intoxicated birds treated with 200 mg/kg b.w of HEPA.

3.3. Oxidative Stress Biomarker

As recorded in Table 3, oral administration of AS at 75 mg/kg b.w for 60 consecutive days caused a significant decrease in the levels of proteins in the liver, and the activities of SOD, CAT and POD, as compared to group 1. However, the co-administration of HEPA at different levels with 75 mg/kg b.w increased in a dose-dependent manner the values of all these oxidative stress parameters. The inverse was recorded for MDA concentration (Table 3).

3.4. Biochemical Parameters

The concentration of ALT, AST, Urea, Creatinine, protein and cholesterol in birds exposed to AS and treated with HEPA are reported in Table 4. Oral administration of AS at 75 mg/kg b.w induced a significant (p < 0.05) increase in serum ALT, AST, Urea, Creatinine concentration. The opposite trend was recorded for total protein and cholesterol concentration. In general, HEPA administration significantly (p < 0.05) decreased levels of hepato and nephrotoxicity markers. As compared to group 2; the inverse was observed with the total protein and cholesterol concentration.

3.5. Histological Analysis

Histological alteration of liver of control and treated quails are reported in Figure 1.

Figure 1. Histopathological alteration of liver of control and treated quails. 1) Liver section of control quail showing a normal hepatocytes. Notice the hepatic sinusoid (S) lined by endothelium (arrow head) and kupffer cells (H & E ×400); 2) Quail treatment with AS liver tissue section (75 mg of kg∙bwt1) showing desquamation of the epithelial cells (arrows) of the bile ductless and focal aggregation of the lymphocytes around the branches of the hepatic artery (O) (H & E ×400); 3) Quail treatment liver tissue section (75 mg of AS kg∙bwt1 + 50 mg HEPA kg∙bwt1), showing a number of hepatocytes undergo fatty changes (v), focal aggregation of the lymphocytes (arrow) and multiple necrotic changes (H & E ×400); 4) Quail treatment liver tissue section (75 mg of AS kg∙bwt1 + 100 mg HEPA kg∙bwt1), focal aggregation of the lymphocytes (arrow) (H & E ×400); 5) Quail treatment liver tissue section (75 mg of AS kg∙bwt1 + 200 mg HEPA kg∙bwt1), showing a slight desquamation (H & E ×400).

Table 2. Effects of different levels of HEPA on some growth parameters of male Japanese quail expose to AS.

n = number of animal, a,b,c,dMeans bearing different letters in a row differ significantly at p < 0.05, Group 1: 10 ml/kg of distilled water only negative control group; Group 2: intoxicated birds receiving 75 mg of AS/kg b.w only positive control group.

Table 3. Effects of different levels of HEPA on some oxidatives stress parameters of male Japanese quail.

n = number of animal, a,b,c,dMeans bearing different letters in a row differ significantly at p < 0.05, Group 1: 10 ml/kg of distilled water only negative control group; Group 2: intoxicated birds receiving 75 mg of AS/kg b.w only positive control group.

Table 4. Effects of different levels of HEPA on some blood parameters of male Japanese quail expose to AS (means ± SE).

n = number of animal, a,b,c,dMeans bearing different letters in a row differ significantly at p < 0.05, Group 1: 10 ml/kg of distilled water only negative control group; Group 2: intoxicated birds receiving 75 mg of AS/kg b.w only positive control group.

4. Discussion

The present study revealed that the oral daily administration of AS at the dose of 75 mg/kg bw generated depression, anorexia, diarrhea and dizziness. Similar results were observed by Prakash et al. [39] in Japanese quails fed with food contaminated with endosulfan insecticide. The appearance of these clinical signs and behavioural alterations may be explained by the capacity of AS to inhibit acetyl cholinesterase enzymes (AchE), which cause acetylcholine accumulation in cholinergic synapses. The increased acetylcholine in pituitary gland and hypothalamus by organophosphate induced inhibition of acetylcholine esterase could variably affect anterior pituitary functions and the release of secondary neurotransmitters, especially dopamine or gonadotrophins [40]. A significant decrease in body weight, body weight gain and liver protein was observed in the AS treated groups. This decrease might be associated firstly to the toxic symptoms, such as cholinergic signs and secondly to the decreased feed consumption. This hypophagia may be related to the effects of the active principles (AS) on the central structures involved in the control of feed intake. It could then be suggested that AS may have inhibited this center thus decreasing the feed intake and consequently the body weight gain observed in the work. The reduction of body weight, body weight gain and liver protein could be attributed to systemic toxicity in Japanese quail. Correlation between decreased AChE activity and increased MDA concentration has been previously reported [41].

This study has shown that AS increased the concentration of MDA in liver organ. MDA is a byproduct of lipidperoxidation resulting from interaction of oxygen radicals with polyunsaturated fatty acids residues in membrane phospholipids that damages important biomolecular Naudi et al. [42]. Oxidative damages have been reported to be a key factor in the subcellular damage resulting from pesticide exposure [43]. Thus the high MDA contents in the liver in the AS group are indications of the level of lipoperoxidative changes, reflecting alteration in the structural and, consequently functional status of the organs. Furthermore, increase in lipid peroxidation might have resulted from failure of internal antioxidant system of the body to counteract the ROS being generated [44] as a result of exposure to AS and its ability to penetrate the blood-brain barrier [45]. The increase in MDA concentration in the liver indicates the participation of free radical-induced damage to the organ and this may be responsible for the decrease in the concentration of SOD, CAT and POD, observed in the AS treated group. The lipoperoxidative damage of the liver of the AS group may have altered its structural integrity and functional status consequently affecting the synthesis of these enzymes.

After 60 days, the quail developed significant hepatic damage, with changes in serum levels of ALT and AST, as well as altered concentrations of urea and creatinine, indicative of hepatic and renal damage. These alterations could have been related to lower levels of SOD, CAT and POD, observed in the AS treated group and increased lipoperoxidation. The liver is the main organ involved in the biotransformation of xenobiotics, and is therefore the site of multiple oxidative reactions, with free radical formation [46]. Increase in the levels of serum aminotransferases is known to reflect the severity of liver injury [47]. The leakage of large quantities of enzymes into the blood stream is associated with massive centrilobular necrosis, ballooning degeneration and cellular infiltration of the liver. Serum AST level is related to the function of the hepatic cell and increase in serum level of ALT is due to increased synthesis of this enzyme [48]. The increase in the transaminases is a clear indication of cellular leakage and loss of functional integrity of the membrane resulting from liver damage [49]. The underlying mechanism by which this insecticide exerts their negative effects may be attributed to the production of ROS.

This study demonstrated that pre-treatment of quail with HEPA caused substantial decreases the clinical signs, behavioural alterations, AST and ALT levels at extract concentration of 200 mg∙kg1∙bw. Effective controls of AST level and ALT activity point towards an early improvement in the secretory mechanism of the hepatic cell [50]. The significant reduction in liver enzymes after pre-treatment with HEPA suggests that the extract is hepato-protective.

The histopathological studies in the liver of quail also showed that HEPA reduced the toxicity of AS and preserved the normal histological architecture of the liver tissue. Furthermore, HEPA treatment resulted in a decrease in the number of apoptotic cells. HEPA significantly suppressed lipid peroxidation, compensated deficits in the antioxidant defenses in liver tissue that resulted from AS administration. They suggested that the hepato-protective potential of HEPA in AS toxicity might be due to its antioxidant and anti-apoptotic properties, which could be useful for achieving optimum effects in AS-induced hepatotoxicity.

The decrease in the serum transaminases levels observed in current study provided supportive evidence that pre-treatment with HEPA reduced the severity of toxic injuries caused by AS administration. The reduction in the severity of necrosis and fatty infiltration observed in molecular architecture also showed that HEPA has hepato-protective activity against AS induced damage in these quails. The observed hepato-protection by HEPA suggests that the extract tends to prevent liver damage by preserving hepatocyte membranes thereby, suppressing the leakage of enzymes into the blood stream. The hepato-protective activity of HEPA is similar to the hepato-protective activity against CCl4 exhibited by Acalypharacemosa [51], Vernoniaamygdalina [52] and Rumexcrispus [53].

Elevation in the levels of end products of lipid peroxidation in the liver of quails treated with AS was observed. The increases in MDA and decrease protein levels in these quails livers suggest occurrence of lipid peroxidation. This observation concord to earlier reports that there is an increase in MDA in liver of rats treated with CCl4 which is attributed to enhanced lipid peroxidation, leading to tissue damage and failure of antioxidant defense mechanisms to prevent the formation of excessive free radicals [54] [55]. Pre-treatment with HEPA decreased MDA concentrations and significantly increase protein levels. Thus, suggesting that the mechanism of hepato-protection of HEPA may be attributed to its antioxidant effect and free radical scavenging activity. Hence, eliminating deleterious effects of toxic metabolites from AS and inducing liver cell regeneration. It is possible that lipid peroxides generated by AS treatment may be scavenged by the extract resulting in depression of lipid peroxidation in the liver. The antioxidant and free radical scavenging activity of HEPA could be due to its constituent flavonoids and phenolic compounds Arukwe et al. [56]. Flavonoids are known to be antioxidants, free radical scavengers and anti-lipoperoxidants which cause hepato-protection [57] [58] [59]. The decreased enzymes activities of SOD, CAT and POD in AS-intoxicated quails agree with the findings of [60]. The decrease in enzymes activities in the liver observed in this study was probably in response to increased reactive oxygen species generation induced by AS administration. Similarly, CCl4 may cause oxidative stress and the consequent up-regulation of antioxidant enzymes to render cells more resistant to subsequent oxidative damage [61]. It is known that under oxidative stress some endogenous antioxidant protective factors such as SOD and CAT are activated in the defense against oxidative injury [62] [63].

In this study, pre-treatment with HEPA increased the activities of CAT, SOD and POD that were raised by AS-intoxication. The extract may have scavenged the free radicals generated thereby decreasing lipid peroxidation and oxidative stress in the quail. These results showed that HEPA possesses significant protective effects against AS-induced hepatotoxicity in quail and the hepato-protection appears to be dose dependent. The mechanism of the hepato-protection seems to involve the modulation of the antioxidant enzyme systems. These beneficial effects may be attributed to the individual or combined action of the phyto-constituents present in the extract such as polyphenols and flavonoids.

5. Conclusion

Based on the present study, it can be concluded that HEPA improve the hepatic alterations induced by AS intoxication. The antioxidant properties of these extracts support the bioactive roles of their protective effects on AS toxicity. Therefore, it is pertinent to further determine, isolate and purify the exact bioactive constituents with the potential hepato-protective property.

Acknowledgements

The authors are thankful to Dschang University, Cameroon for providing research facilities for undertaking this work.

Author Contribution Statement

Ngoumtsop Victor Herman: Conceived and designed the experiments; Performed the experiments; Analyzed and interpreted the data; Contributed reagents, materials, analysis tools or data; Wrote the paper.

Ferdinand Ngoula: Conceived and designed the experiments; Analyzed and interpreted the data; Contributed reagents, materials, analysis tools or data; Wrote the paper.

Guiekep Nounamou Arthénice Jemima and Tchoffo Herve: Contributed reagents, materials, analysis tools or data; wrote the paper.

Mutwedu Bwana Valence: Contributed reagents, materials, analysis tools or data.

Cite this paper: Herman, N. , Herve, T. , Jemima, G. , Valence, M. and Ferdinand, N. (2021) Hepato-Preventive Effects of Hydroethanolic Leaves Extract of Persea americana Mill. (Lauraceae) “Avocado” against Antouka Super®Induced Damage in Male Japanese Quail (Coturnix coturnix Japonica). Open Journal of Veterinary Medicine, 11, 41-56. doi: 10.4236/ojvm.2021.111003.
References

[1]   Ngoumtsop, V.H., Ngoula, F., Kenfack, A., et al. (2017) Effects of Oxidative Stress Induced by Antouka Super? (Insecticide) on Some Reproductive Parameters of Male Japanese Quail (Coturnix coturnix Japonica) and Mitigation Strategies Using Aqueous Leaves Extract of Persea americana. Global Veterinaria, 18, 242-249.

[2]   Abel, E., Arslan-Acaroz, D., Demirel, H.H., Kucukkurt, I. and Ince, S. (2018) The Subchronic Exposure to Malathion, an Organophosphate Pesticide, Causes Lipid Peroxidation, Oxidative Stress, and Tissue Damage in Rats: The Protective Role of Resveratrol. Toxicology Research, 7, 503-512.
https://doi.org/10.1039/C8TX00030A

[3]   Nessiem, A.L., Bassily, N.S. and Metwally, S.A. (2003) Comparative Histopathological Evaluation of Permethrin, Pirimiphos Methyl and Bendiocarb Toxicities in Testes, Liver and Kidney of Rat. Egyptian Journal of Hospital Medicine, 11, 58-73.

[4]   Hallenbeck, W.H. and Cunningham-Burns, K.M. (2014) Pesticides and Human Health. Springer-Verlag, New York.

[5]   Kingsley, C. and Patrick-Iwuanyanwu (2014) Biochemical and Histological Changes in Liver and Kidney in Male Wistar Albino Rats Following Exposure to Solignum: A Permethrin Containing Wood Preservative Iniobong A. Charles. Journal of Xenobiotics, 4, 45-96.
https://doi.org/10.4081/xeno.2014.4596

[6]   Heikal, A.T., Mossa, H., Ibrahim, A.W. and Abdel-Hamid, H.F. (2014) Hepato-Renal Damage and Oxidative Stress Associated with Pirimiphos-Methyl Exposure in Male Mice. Oxidative and Antioxidant Medicine Sciences, 3, 109-117.
https://doi.org/10.5455/oams.260514.or.064

[7]   Mansour, S.A. and Mossa, A.H. (2009) Lipid Peroxidation and Oxidative Stress in Rat Erythrocytes Induced by Chlorpyrifos and the Protective Effect of Zinc. Pesticide Biochemical Physiological, 9, 4-9.

[8]   Arslan, H.O., Herrera, C., Malama, E., Siuda, M., Leiding, C. and Bollwein, H. (2019) Effect of the Addition of Different Catalase Concentrations to a TRIS-Egg Yolk Extender on Quality and In Vitro Fertilization Rate of Frozen-Thawed Bull Sperm. Cryobiology, 91, 40-52.
https://doi.org/10.1016/j.cryobiol.2019.10.200

[9]   Mossa, A.T., Refaie, A.A., Ramadan, A. and Bouajila, J. (2003) Amelioration of Prallethrin-Induced Oxidative Stress and Hepatotoxicity in Rat by the Administration of Origanum majorana Essential Oil. Biomedical Research International, 1, 11.
https://doi.org/10.1155/2013/859085

[10]   Mossa, A.H., Swelam, E.S. and Mohafrash, S.M.M. (2015) Sub-Chronic Exposure to Fipronil Induced Oxidative Stress, Biochemical and Histopathological Changes in the Liver and Kidney of Male Albino Rats. Toxicology Reports, 2, 775-784.
https://doi.org/10.1016/j.toxrep.2015.02.009

[11]   Gutteridge, J.M. and Halliwell, B. (2010) Antioxidants: Molecules, Medicines, and Myths. Biochemical and Biophysical Research Communications, 393, 561-564.
https://doi.org/10.1016/j.bbrc.2010.02.071

[12]   Acaroz, U., Ince, S., Arslan-Acaroz, D., et al. (2018) The Ameliorative Effects of Boron against Acrylamide-Induced Oxidative Stress, Inflammatory Response, and Metabolic Changes in Rats. Food and Chemical Toxicology, 118, 745-752.
https://doi.org/10.1016/j.fct.2018.06.029

[13]   Mimić-Oka, J., Simić, T., Djukanović, L., Reljić, Z. and Davicević, Z. (1999) Alteration in Plasma Antioxidant Capacity in Various Degrees of Chronic Renal Failure. Clinical Nephrology, 5, 233-241.

[14]   Nice, D. (1997) Antioxidant Based Nutraceuticals. In: Yalpani, M., Ed., New Technologies for Healthy Foods and Nutraceuticals, Science Publishers, Shrewsbury, 23-105.

[15]   Adeyemi, O.O., Okpo, O.S. and Ogunti, O.O. (2012) Analgesic and Anti-Inflammatory Effects of the Aqueous Extract of Leaves of Persea americana Mill. (Lauraceae). Fitoterapia, 73, 375-380.
https://doi.org/10.1016/S0367-326X(02)00118-1

[16]   Korać, R.R. and Khambholja, K.M. (2011) Potential of Herbs in Skin Protection from Ultraviolet Radiation. Pharmacognosy Reviews, 5, 164-173.
https://doi.org/10.4103/0973-7847.91114

[17]   Raharjo, S.H.T., Gomez-Lim, W.M.A., Padilla, G. and Litz, R.E. (2008) Recovery of Avocado (Persea americana Mill.) Plants Transformed with the Antifungal Plant Defense in Gene PDF12. In Vitro Cellular Developmental Biology, 44, 254-262.
https://doi.org/10.1007/s11627-008-9117-2

[18]   Anaka, O.A., Ozolua, R.I. and Okpo, S.O. (2009) Effect of the Aqueous Seed Extract of Persea americana Mill. (Lauraceae) on the Blood Pressure of Sprague Dawley Rats. African Journal Pharmacy Pharmacology, 3, 485-490.

[19]   Kosińska, A., Karamác, M., Estrella, I., Hernández, T., Bartolomé, B. and Dykes, A.G. (2012) Phenolic Compound Profiles and Antioxidant Capacity of Persea americana Mill. Peels and Seeds of Two Varieties. Journal Agricultural Food Chemistry, 60, 4613-4619.
https://doi.org/10.1021/jf300090p

[20]   Hidalgo, M., Sánchez-Moreno, C. and Pascual-Teresa, S. (2010) Flavonoid-Flavonoid Interaction and Its Effect on Their Antioxidant Activity. Food Chemistry, 12, 691-696.
https://doi.org/10.1016/j.foodchem.2009.12.097

[21]   Rodríguez-Carpena, J., Morcuende, D., Andrade, M.J., Kylli, P. and Estéve, M. (2011) Avocado (Persea americana Mill.) Phenolics, in Vitro Antioxidante and Antimicrobial Activities, and Inhibition of Lipid and Protein Oxidation in Porcine Patties. Journal Agricultural Food Chemistry, 59, 5625-5635.
https://doi.org/10.1021/jf1048832

[22]   Ekor, M., Adepoju, G.K.A. and Epoyun, A.A. (2006) Protective Effect of the Methanolic Leaf Extract of Persea americana (Avocado) against Paracetamol-Induced Acute Hepatotoxicity in Rats. International Journal of Pharmacology, 2, 416-420.
https://doi.org/10.3923/ijp.2006.416.420

[23]   Owolabi, M.A., Coker, B.A.H. and Jaja, S.I. (2010) Bioactivity of the Phytoconstituents of the Leaves of Persea americana. Journal of Medicinal Plants Research, 4, 1130-1135.

[24]   Rice-Evans, C. (1995) Plant Polyphenols: Free Radical Scavengers or Chain-Breaking Antioxidants. Biochemical and Social Symposium, 6, 103-116.
https://doi.org/10.1042/bss0610103

[25]   Rice-Evans, C.A. and Miller, N.J. (1996) Antioxidant Activities of Flavonoids as Bioactive Components of Food. Biochemical and Social Transdisciplinary, 24, 790-795. https://doi.org/10.1042/bst0240790

[26]   Rice-Evans, C.A., Miller, N.J. and Paganga, G. (1996) Structure-Antioxidant Activity Relationships of Flavonoids and Phenolic Acid. Free Radical Biology & Medicine, 20, 933-956.
https://doi.org/10.1016/0891-5849(95)02227-9

[27]   Bruck, R., Hershkoviz, R., Lider, O., Aeed, H., Zaidel, L. and Matas, Z. (2007) Flavonoid Metabolites in Urine after Oral Administration of the Aqueous Extract of Persea americana to Rats.

[28]   Conwell, D.G., Jones, K.H., Jiang, Z., Lantry, L.E., Kohar, et al. (1998) Cytotoxicity of Tocopherols and Their Quinines in Drug-Sensitive and Multidrug-Resistant Leukemia Cells. Lipids Journal, 3, 295-301.
https://doi.org/10.1007/s11745-998-0208-8

[29]   Cook, N.C. and Samman, S. (1996) Flavonoids Chemistry, Metabolism, Cardioprotective Effects, and Dietary Sources. Journal of Nutrition and Biochemical, 7, 66-76.
https://doi.org/10.1016/S0955-2863(95)00168-9

[30]   Owolabi, M.A., Bruck, R., Hershkoviz, R., Lider, et al. (2007) Flavonoid Metabolites in Urine after Oral Administration of the Aqueous Extract of Persea americana to Rats. Journal of Natural Medicine, 6, 200-204.
https://doi.org/10.1007/s11418-006-0122-7

[31]   Rame-Tiendrebeogo, A.A., Tibiri, A., Lompo, M., Millogo-Kone, H. and Guissou, P. (2012) Antioxidative and Bacterial Activities of Phenolics Compounds from Ficus sur Forssk and Fircus sycomorus L. (Moraceae): Potential for Sickle Cell Disease Treatment in Burkina Faso. International Journal of Biological and Chemistry Sciences, 6, 328-336.
https://doi.org/10.4314/ijbcs.v6i1.29

[32]   EEC (1986) Council Directive 86/609/EEC of 24 November 1986 on the Approximation of Laws, Regulations and Administration Provisions of the Member States Regarding the Protection of Animals Used for Experimental and Other Scientific Purposes. Official Journal European Committed, 35, 1-29.

[33]   Hayes, W.J. and Laws, E.R. (1998) Handbook of Pesticide Toxicology. Academic Press, Cambridge, 185.

[34]   Tchoffo, H., Kana, J.R., Ngoula, F., Ngoumtsop, V.H., et al. (2019) Effects of Ginger (Zingiber officinale, Roscoe) Essential Oil on Growth and Laying Performances, Serum Metabolites, and Egg Yolk Antioxidant and Cholesterol Status in Laying Japanese Quail. Journal of Veterinary Medicine, 2019, Article ID: 7857504.
https://doi.org/10.1155/2019/7857504

[35]   Habbu, P.V., Shastry, R.A., Mahadevan, K.M., Hanumanthachar, J. and Das, S.K. (2008) Protective and Antioxidant Effects of Argyreia speciosa in Quails. African Journal and Alternative Medicine, 5, 158-164.
https://doi.org/10.4314/ajtcam.v5i2.31268

[36]   Dimo, T., Tsala, D.E., Dzeufiet, D.P.D., Penlap, B.V. and Njifutie, N. (2006) Effects of Alafia multiflora Stap on Lipid Peroxidation and Antioxidant Enzyme Status in Carbon Tetrachloride-Treated Quails. Pharmacology Online, 2, 76-89.

[37]   Kodjo, N., Atsafack, S.S., Njateng, S.S.G., Sokoudjou, B.J. and Kuiate, R.J. (2016) Antioxidant Effect of Aqueous Extract of Curcuma longa Rhizomes (Zingiberaceae) in the Typhoid Fever Induced in Wistar Rats Model. Journal of Applied Medicine and Pharmacological Sciences, 7, 1-13.
https://doi.org/10.9734/JAMPS/2016/24949

[38]   Sajeeth, C.I., Manna, P.K. and Manavalan, R. (2011) Antioxidant Activity of Polyherbal Formulation on Streptozotocin Induced Diabetes in Experimental Animals. Der Pharmacia Sinica, 2, 220-226.

[39]   Prakash, P.J., Rajashekher, G., Krishnappa, H., Sulaiman, S.M. and Rao, K.V. (2009) Acute Toxic Effects of Endosulfan 35 EC (Endocel) upon Oral Gavage and Dietary Admixture in Japanese Quails. Research Journal of Environmental Toxicology, 3, 124-131.
https://doi.org/10.3923/rjet.2009.124.131

[40]   Sarkar, R., Mohana, K.P. and Chowdhury, H. (2000) Effects of an Organophosphate Pesticide, Quinalphos, on the Hypothalamo-Pituitary-Gonadal Axis in Adult Male Rats. Journal of Reproduction and Fertility, 118, 29-38.
https://doi.org/10.1530/jrf.0.1180029

[41]   Rastogi, S.K., Satyanarayan, P.V.V., Ravishankar, D. and Tripathi, S. (2007) A Study on Oxidative Stress and Antioxidant Status of Agricultural Workers Exposed to Organophosphorus Insecticides during Spraying. Indian Journal of Occupational Environmental Medicine, 13, 131-134.
https://doi.org/10.4103/0019-5278.58916

[42]   Naudi, A.M., Jove, V., Ayala, R., Cabre, M., Portero-Otin, et al. (2013) Non-Enzymatic Modification of Aminophospholipids by Carbonyl-Amine Reactions. International Journal of Molecular Sciences, 14, 3285-3313.
https://doi.org/10.3390/ijms14023285

[43]   Kumar, V., Tripathi, V.K., Singh, A.K., Lohani, M. and Kuddus, M. (2013) Trans-Resveratrol Restores the Damages Induced by Organophosphate Pesticide-Monocrotophos in Neuronal Cells. Toxicology International, 20, 48-55.
https://doi.org/10.4103/0971-6580.111571

[44]   Umosen, J.A., Ambali, S.F., Ayo, J.O., Mohammed, B. and Uchendu, C. (2012) Alleviating Effects of Melatonin on Oxidative Changes in the Testes and Pituitary Glands Evoked by Subacute Chlorpyrifos Administration in Wistar Rats. Asian Pacific Journal Tropical Biomedicine, 2, 645-850.
https://doi.org/10.1016/S2221-1691(12)60113-0

[45]   EL-Hossary, G.G., Mansour, S.M. and Mohamed, A.S. (2009) Neurotoxic Effects of Chlorpyrifos and the Possible Protective Role of Antioxidant Supplements: An Experimental Study. Journal of Applied Sciences Research, 5, 1218-1222.

[46]   Raquel, J., Gabriel, L.O., Celso, P. and Claudriana, L. (2012) Attribution Evaluation of Biochemical, Hematological and Oxidative Parameters in Mice Exposed to the Herbicide Glyphosate-Roundup. Interdisciplinary Toxicology, 5, 133-140.
https://doi.org/10.2478/v10102-012-0022-5

[47]   Lin, S.C., Yao, C.J., Lin, C.C. and Lin, H.Y. (1996) Hepatoprotective Activity of Taiwan Folk Medicine: Eclipta prostrata Linn. against Various Hepatotoxins Induced Acute Hepatotoxicity. Phytotherapy Research, 10, 483-490.

[48]   Moss, D.W. and Butterworth, P.J. (1974) Enzymology and Medicine. 139.

[49]   Saraswat, B., Visen, P.K., Patnaik, K.G. and Dhawan, N.B. (1993) Anticholestatic Effect of Picroliv, Active Hepatoprotective Principle of Picrorhiza kurrooa, against Carbon Tetrachloride Induced Cholestasis. Indian Journal of Experimental Biology, 31, 316-318.

[50]   Gupta, M., Mazumder, U.K., Kumar, S.T., Gomathi, P. and Kumar, S.R. (2004) Antioxidant and Hepatoprotective Effects of Bauhinia racemosa against paracetamol and carbon tetrachloride induced liver damage in rats. Iranian Journal of Pharmacological Therapeutics, 3, 12-20.

[51]   Iniaghe, O.S., Malomo, O.J., Adebayo and Arise, O.R. (2008) Evaluation of the Antioxidant and Hepatoprotective Properties of the Methanolic Extract of Acalypha racemosa Leaf in Carbon Tetrachloride-Treated Rats. African Journal of Biotechnology, 7, 1716-1720.
https://doi.org/10.5897/AJB08.229

[52]   Adesanoye, A.O. and Farombi, O.E. (2010) Hepatoprotective Effects of Vernonia amygdalina (Astereaceae) in Rats Treated with Carbon Tetrachloride. Experimental Toxicology and Pathology, 62, 197-206.
https://doi.org/10.1016/j.etp.2009.05.008

[53]   Maksimovic, Z., Kovacevic, N., Lakusic, B. and Cebovic, T. (2011) Antioxidant Activity of Yellow Dock (Rumex crispus L., Polygonaceae) Fruit Extract. Phytotherapy Research, 25, 101-105.
https://doi.org/10.1002/ptr.3234

[54]   Shenoy, A.K., Somayaji, N.S. and Bairy, L.K. (2001) Hepatoprotective Effect of Ginkgo biloba against CCl4-Induced Hepatic Injury in Rats. Indian Journal of Pharmacology, 33, 260-266.

[55]   Wang, J.B., Liu, T.C., Tseng, Y.C., Wu, P.C. and Yu, R.Z. (2004) Hepatoprotective and Antioxidant Effects of Bupleurum kaoi Liu (Chao et Chuang) Extract and Its Fractions Fractionated Using Supercritical CO2 on CCl4-Induced Liver Damage. Food Chemical and Toxicology, 42, 609-617.
https://doi.org/10.1016/j.fct.2003.11.011

[56]   Arukwe, U., Amadi, A.B., Duru, C.K.M., Aguomo, et al. (2012) Chemical Composition of Persea americana Leaf, Fruit and Seed. International Journal Research and Applied Sciences, 11, 349-356.

[57]   Khalid, J.H., Sheikh, S.A. and Anwar, G.H. (2002) Protective Effect of Rutin on Paracetamol- and CCl4-Induced Hepatotoxicity in Rodents. Fitoterapia, 73, 557-563.
https://doi.org/10.1016/S0367-326X(02)00217-4

[58]   Al-Qarawi, A.A., Mousa, M.H., Ali, H.B., Abdel-Rahman, H. and El-Moug, A.S. (2004) Protective Effect of Extracts from Dates (Phoenix dactylifera L.) on Carbon Tetrachloride-Induced Hepatotoxicity in Rats. International Journal of Applied Research Veterinary Medicine, 2, 176-180.

[59]   Mankani, L.K., Krishna, V., Manjunatha, B.K., MVidya, et al. (2005) Evaluation of Hepatoprotective Activity of Stem Bark of Pterocarpus marsupium Roxb. Indian Journal of Pharmacology, 37, 165-168.
https://doi.org/10.4103/0253-7613.16213

[60]   Harisch, G. and Meyer, W. (1985) Studies on Tissue Distribution of Glutathione and on Activities of Glutathione-Related Enzymes after Carbon Tetrachlo-ride-Induced Liver Injury. Research Communications in Chemical Pathology and Pharmacology, 47, 399-414.

[61]   Halliwell, B. (2000) The Antioxidant Paradox. The Lancet, 355, 1179-1180.
https://doi.org/10.1016/S0140-6736(00)02075-4

[62]   Kyle, E.M., Miccadei, S., Nakae, D. and Farber, L.J. (1987) Superoxide Dismutase and Catalase Protect Cultured Hepatocytes from the Cytotoxicity of Acetaminophen. Biochemical and Biophysical Research Communications, 149, 889-896.
https://doi.org/10.1016/0006-291X(87)90491-8

[63]   John, S., Kale, M., Rathore, N. and Bhatnagar, D. (2001) Protective Effect of Vitamin E in Dimethoate and Malathion Induced Oxidative Stress in Rat Erythrocytes. Journal of Nutrition and Biochemical, 12, 500-504.
https://doi.org/10.1016/S0955-2863(01)00160-7

 
 
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