Schiff base SH11 with tuberculostatic and radical scavenging activities against INH-induced oxidative hepatic damage
Affiliation(s)
Department of Pharmacology, Animal Physiology and Physiological Chemistry, Faculty of Veterinary Medicine, Trakia University, Students Campus, Stara Zagora, Bulgaria. Department of Medical Chemistry and Biochemistry, Faculty of Medicine, Trakia University, Stara Zagora, Bulgaria. Institute of Organic Chemistry, Bulgarian Academy of Sciences, Sofia, Bulgaria.
Department of Pharmacology, Animal Physiology and Physiological Chemistry, Faculty of Veterinary Medicine, Trakia University, Students Campus, Stara Zagora, Bulgaria. Department of Medical Chemistry and Biochemistry, Faculty of Medicine, Trakia University, Stara Zagora, Bulgaria. Institute of Organic Chemistry, Bulgarian Academy of Sciences, Sofia, Bulgaria.
ABSTRACT
By in vitro visible electron paramagnetic resonance (EPR) spectrophotometry method we demonstrated that N-isonicotinoyl-N’-(3-etoxy-2-hydroxybenzaldehyd) hydrazone (SH11) exhibits radical scavenging activity (SSA). Malondialdehyde (MDA) in mice treated with INH was increased (2.578 ± 0.349 mM vs. 2.024 ± 0.164 μM, p < 0.001), while both superoxide dismutase (SOD) (1.583 ± 0.562 USOD/mg Pr vs. 2.273 ± 0.317 USOD/mg Pr, p < 0.05) and catalase (CAT) (30.176 ± 7.300 UCAT/mg Pr, vs. 47.070 ± 16.490 UCAT/mg Pr, p < 0.05) were decreased, compared to the untreated controls. The combination INH + SH11 (30 mg/kg p.o.) showed reduced levels of MDA, compared to the INH-treated (mean 2.291 ± 0.025 μM than 2.578 ± 0.349, p < 0.05). The combination with the lowest reduction of SOD compared to the controls was 151 mg/kg i.p. INH + 30 mg/kg p.o. SH11, but there was a significant difference in SOD activities between the group treated with this combination and the untreated controls (p < 0.05). The most effective combination, with CAT levels, close to the controls was 151 mg/kg i.p. INH + 30 mg/kg p.o. SH11.
By in vitro visible electron paramagnetic resonance (EPR) spectrophotometry method we demonstrated that N-isonicotinoyl-N’-(3-etoxy-2-hydroxybenzaldehyd) hydrazone (SH11) exhibits radical scavenging activity (SSA). Malondialdehyde (MDA) in mice treated with INH was increased (2.578 ± 0.349 mM vs. 2.024 ± 0.164 μM, p < 0.001), while both superoxide dismutase (SOD) (1.583 ± 0.562 USOD/mg Pr vs. 2.273 ± 0.317 USOD/mg Pr, p < 0.05) and catalase (CAT) (30.176 ± 7.300 UCAT/mg Pr, vs. 47.070 ± 16.490 UCAT/mg Pr, p < 0.05) were decreased, compared to the untreated controls. The combination INH + SH11 (30 mg/kg p.o.) showed reduced levels of MDA, compared to the INH-treated (mean 2.291 ± 0.025 μM than 2.578 ± 0.349, p < 0.05). The combination with the lowest reduction of SOD compared to the controls was 151 mg/kg i.p. INH + 30 mg/kg p.o. SH11, but there was a significant difference in SOD activities between the group treated with this combination and the untreated controls (p < 0.05). The most effective combination, with CAT levels, close to the controls was 151 mg/kg i.p. INH + 30 mg/kg p.o. SH11.
Cite this paper
Georgieva, N. , Yaneva, Z. , Nikolova, G. and Simova, S. (2012) Schiff base SH11 with tuberculostatic and radical scavenging activities against INH-induced oxidative hepatic damage. Advances in Bioscience and Biotechnology, 3, 1068-1075. doi: 10.4236/abb.2012.327130.
Georgieva, N. , Yaneva, Z. , Nikolova, G. and Simova, S. (2012) Schiff base SH11 with tuberculostatic and radical scavenging activities against INH-induced oxidative hepatic damage. Advances in Bioscience and Biotechnology, 3, 1068-1075. doi: 10.4236/abb.2012.327130.
References
[1] Mahesh, C., Shailesh, P. and Mitesh, J. (2010) Recent Development and Future Perspective of Antitubercular Therapy. Anti-Infective Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Infective Agents), 9, 59-103. doi:10.2174/187152110791383779 [2] Van Halsema, C.L., Fielding, K.L., Chihota, V.N., Russell, E.C., Lewis, J.J., Churchyard, G.J. and Grant, A.D. (2010) Tuberculosis outcomes and drug susceptibility in individuals exposed to isoniazid preventive therapy in a high HIV prevalence setting. AIDS, 24, 1051-1055. doi:10.1097/QAD.0b013e32833849df [3] Ravi, V., Patel, S.S., Verma, N.K., Dutta, D. and Saleem, T.S.M. (2010) Hepatoprotective activity of Bombax ceiba linn against isoniazid and rifampicin-induced toxicity in experimental rats. International Journal of Applied Research in Natural Products, 3, 19-26. [4] Hearn, M.J., Cynamon, M.H., Chen, M.F., Coppins, R., Davis, J., Kang, H.J., Noble, A., Tu-Sekine, B., Terrot, M.S., Trombino, D., Thai, M., Webster, E.R. and Wilson, R. (2009) Preparation and antitubercular activities in vitro and in vivo of novel Schiff bases of isoniazid. European Journal of Medicinal Chemistry, 44, 4169-4178. doi:10.1016/j.ejmech.2009.05.009 [5] Georgieva, N. and Gadjeva, V. (2002) Isonicotinoyl-hydrazone analogs of isoniazid: Relationship between superoxide scavenging and tuberculostatic activities. Biochemistry (Moscow), 67, 588-591. doi:10.1023/A:1015558514432 www.ncbi.nlm.nih.gov/pubmed/12059780 [6] Georgieva, N., Gadjeva, V., Tolekova, A. and Dimitrov, D. (2005) Hepatoprotective effect of isonicotinoylhydrazone SH7 against chronic isoniazid toxicity. Die Pharmazie, 60, 138-141. www.ncbi.nlm.nih.gov/pubmed/15739904 [7] Varbanova, S. and Georgieva, N. (1993) New isonicotino-ylhydrazones with tuberculostatic action. Veterinary Science, 27, 81-85. [8] Geran, R.S., Greenberg, N.H., Macdonald, M.M., Schumacher, A.M. and Abbott, B.J. (1972) Protocols for screening chemical agents and natural products against animal tumors and other biological systems. Cancer Chemotherapy Reports, 13, 1-87. [9] Lowry, O.H., Rosenbrough, N.J., Farr, A.L. and Randall, R.J. (1951) Protein measurement with the Folin Phenol Reagent. The Journal of Biological Chemistry, 193, 265-275. www.ncbi.nlm.nih.gov/pubmed/14907713 [10] Placer, Z.A., Cushman, L.L. and Jonson, B.C. (1966) Estimation of product of lipid peroxidation (Malonyl Dialdehide) in Biochemcal Systems. Analitical Biochemistry, 16, 359-364. doi:10.1016/0003-2697(66)90167-9 [11] Sun, Y., Oberley, L.W. and Li, Y. (1988) A simple method for clinical assay of superoxide dismutase. Clinical Chemistry, 34, 497-500. [12] Beers, R. and Sizer, T. (1952) Spectrophotometric metod for measuring the breakdown of hydrogenperoxide by catalase. The Journal of Biological Chemistry, 195, 133-138. [13] Fridovich, I. (1975) Superoxide dismutases. Annual Review of Biochemistry, 44, 147-159. doi:10.1146/annurev.bi.44.070175.001051 [14] Bhadauria, S., Mishra, R., Kanchan, R., Tripathi, C., Srivastava, A., Tiwari, A. and Sharma, S. (2010) Isoniazid-induced apoptosis in HepG2 cells: Generation of oxidative stress and Bcl-2 down-regulation. Toxicology Mechanisms and Methods, 20, 242-251. doi:10.3109/15376511003793325 [15] Afanas’ev, I. (2010) Signaling of reactive oxygen and nitrogen species in diabetes mellitus. Oxidative Medicine and Cellular Longevity, 3, 361-373. doi:10.4161/oxim.3.6.14415 [16] Santhosh, S., Sini, T.K., Anandan, R. and Mathee, P.T. (2007) Hepatoprotective activity of chitosan against isoniazid and rifampicin-induced toxicity in experimental rats. European Journal of Pharmacology, 572, 69-73. doi:10.1016/j.ejphar.2007.05.059 [17] Georgieva, N.V. (2005) Oxidative stress as a factor of disrupted ecological oxidative balance in biological systems—A Review. Bulgarian Journal of Veterinary Medicine, 8, 1-11. http://tru.uni-sz.bg/bjvm/vol08-no01-01.pdf
[1] Mahesh, C., Shailesh, P. and Mitesh, J. (2010) Recent Development and Future Perspective of Antitubercular Therapy. Anti-Infective Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry-Anti-Infective Agents), 9, 59-103. doi:10.2174/187152110791383779 [2] Van Halsema, C.L., Fielding, K.L., Chihota, V.N., Russell, E.C., Lewis, J.J., Churchyard, G.J. and Grant, A.D. (2010) Tuberculosis outcomes and drug susceptibility in individuals exposed to isoniazid preventive therapy in a high HIV prevalence setting. AIDS, 24, 1051-1055. doi:10.1097/QAD.0b013e32833849df [3] Ravi, V., Patel, S.S., Verma, N.K., Dutta, D. and Saleem, T.S.M. (2010) Hepatoprotective activity of Bombax ceiba linn against isoniazid and rifampicin-induced toxicity in experimental rats. International Journal of Applied Research in Natural Products, 3, 19-26. [4] Hearn, M.J., Cynamon, M.H., Chen, M.F., Coppins, R., Davis, J., Kang, H.J., Noble, A., Tu-Sekine, B., Terrot, M.S., Trombino, D., Thai, M., Webster, E.R. and Wilson, R. (2009) Preparation and antitubercular activities in vitro and in vivo of novel Schiff bases of isoniazid. European Journal of Medicinal Chemistry, 44, 4169-4178. doi:10.1016/j.ejmech.2009.05.009 [5] Georgieva, N. and Gadjeva, V. (2002) Isonicotinoyl-hydrazone analogs of isoniazid: Relationship between superoxide scavenging and tuberculostatic activities. Biochemistry (Moscow), 67, 588-591. doi:10.1023/A:1015558514432 www.ncbi.nlm.nih.gov/pubmed/12059780 [6] Georgieva, N., Gadjeva, V., Tolekova, A. and Dimitrov, D. (2005) Hepatoprotective effect of isonicotinoylhydrazone SH7 against chronic isoniazid toxicity. Die Pharmazie, 60, 138-141. www.ncbi.nlm.nih.gov/pubmed/15739904 [7] Varbanova, S. and Georgieva, N. (1993) New isonicotino-ylhydrazones with tuberculostatic action. Veterinary Science, 27, 81-85. [8] Geran, R.S., Greenberg, N.H., Macdonald, M.M., Schumacher, A.M. and Abbott, B.J. (1972) Protocols for screening chemical agents and natural products against animal tumors and other biological systems. Cancer Chemotherapy Reports, 13, 1-87. [9] Lowry, O.H., Rosenbrough, N.J., Farr, A.L. and Randall, R.J. (1951) Protein measurement with the Folin Phenol Reagent. The Journal of Biological Chemistry, 193, 265-275. www.ncbi.nlm.nih.gov/pubmed/14907713 [10] Placer, Z.A., Cushman, L.L. and Jonson, B.C. (1966) Estimation of product of lipid peroxidation (Malonyl Dialdehide) in Biochemcal Systems. Analitical Biochemistry, 16, 359-364. doi:10.1016/0003-2697(66)90167-9 [11] Sun, Y., Oberley, L.W. and Li, Y. (1988) A simple method for clinical assay of superoxide dismutase. Clinical Chemistry, 34, 497-500. [12] Beers, R. and Sizer, T. (1952) Spectrophotometric metod for measuring the breakdown of hydrogenperoxide by catalase. The Journal of Biological Chemistry, 195, 133-138. [13] Fridovich, I. (1975) Superoxide dismutases. Annual Review of Biochemistry, 44, 147-159. doi:10.1146/annurev.bi.44.070175.001051 [14] Bhadauria, S., Mishra, R., Kanchan, R., Tripathi, C., Srivastava, A., Tiwari, A. and Sharma, S. (2010) Isoniazid-induced apoptosis in HepG2 cells: Generation of oxidative stress and Bcl-2 down-regulation. Toxicology Mechanisms and Methods, 20, 242-251. doi:10.3109/15376511003793325 [15] Afanas’ev, I. (2010) Signaling of reactive oxygen and nitrogen species in diabetes mellitus. Oxidative Medicine and Cellular Longevity, 3, 361-373. doi:10.4161/oxim.3.6.14415 [16] Santhosh, S., Sini, T.K., Anandan, R. and Mathee, P.T. (2007) Hepatoprotective activity of chitosan against isoniazid and rifampicin-induced toxicity in experimental rats. European Journal of Pharmacology, 572, 69-73. doi:10.1016/j.ejphar.2007.05.059 [17] Georgieva, N.V. (2005) Oxidative stress as a factor of disrupted ecological oxidative balance in biological systems—A Review. Bulgarian Journal of Veterinary Medicine, 8, 1-11. http://tru.uni-sz.bg/bjvm/vol08-no01-01.pdf