Hepatoprotective effect of isonicotinoylhydrazone SH7 against chronic isoniazid toxicity.
This study was carried out to investigate whether 3,5-dichloro-salicylaldehyde isonicotinoyl hydrazone (SH7), an analogue of the antituberculosis drug isoniazid (INH), recently synthesized in our laboratory, could prevent isoniazid-induced liver damage. Forty-two white healthy mice were treated, once daily for 30 days, with solutions of INH, SH7 and combinations of them at doses of 7.5 mg/kg p.o. and 15 mg/kg p.o. At the end of this period, livers were harvested for histopathological analysis. The levels of lipid peroxidation products (MDA) and the activities of antioxidant defense enzymes, superoxide dismutase (SOD) and catalase (CAT), were also measured in the liver homogenates. Treatments with combinations of INH and SH7 decreased the levels of MDA, normalized the previously depressed levels of SOD and CAT and prevented isoniazid-induced liver damages. A previously demonstrated tuberculostatic and superoxide scavenger activity (SSA) of the isonicotinoylhydrazone SH7 and results from the present study thus set out a proposal for a new isoniazid/SH7 combination therapy designed to provide hepatoprotection.
Georgieva
N
N
Department of Veterinary Physiology and Physiological Chemistry, Faculty of Veterinary Medicine, Trakia University, Stara Zagora, Bulgaria.
Gadjeva
V
V
Tolekova
A
A
Dimitrov
D
D
D000818:Animals; D000995:Antitubercular Agents / Q000633:toxicity*; D002374:Catalase / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology / Q000517:prevention & control*; D007538:Isoniazid / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology* / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D013482:Superoxide Dismutase / Q000378:metabolism
D000995:Antitubercular Agents; C498401:isonicotinoylhydrazone SH7; D008315:Malondialdehyde; D002374:Catalase; D013482:Superoxide Dismutase; D007538:Isoniazid