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Isoniazid is one of the most commonly used drugs to treat tuberculosis. Its administration is associated with a high incidence of hepatotoxicity. The aim of this study was to establish the protective effects of taurine against cytotoxicity induced by isoniazid and its suspected toxic metabolite hydrazine in isolated rat hepatocytes by measuring reactive oxygen species (ROS ) formation, lipid peroxidation, mitochondrial depolarisation, reduced glutathione (GSH), and oxidised glutathione (GSSG). Isoniazid caused no significant ROS formation in normal hepatocytes, but in glutathione-depleted cells it was considerable. Hydrazine caused ROS formation and lipid peroxidation in both intact and glutathione-depleted cells. Both isoniazid and hydrazine caused mitochondrial membrane depolarisation. Hydrazine lowered cellular GSH reserve and increased GSSG. Taurine (200 (xmol L^sup -1^) and N-acetylcysteine (200 (xmol L^sup -1^) effectively countered the toxic effects of isoniazid and/or hydrazine by decreasing ROS formation, lipid peroxidation, and mitochondrial damage. Taurine prevented depletion of GSH and lowered GSSG levels in hydrazine-treated cells. This study suggests that the protective effects of taurine against isoniazid and its intermediary metabolite hydrazine cytotoxicity in rat hepatocytes could be attributed to antioxidative action.

KEYWORDS: cytotoxicity, glutathione, lipid peroxidation, mitochondria, N-acetylcysteine, oxidative stress

Sazetak

CITOPROTEKTIVNO DJELOVANJE TAURINA NA TOKSICNOST IZONIAZIDAI HIDRAZINA U IZOLIRANIM STANICAMA STAKORA

Izoniazid je jedan od najcescih lijekova za tuberkulozu, ali se njegova primjena povezuje s veoma ucestalom hepatotoksicnosti. Cilj je ovog istrazivanja bio ocijeniti djelotvornost taurina u zastiti izoliranih hepatocita stakora od citotoksicnosti izazvane izoniazidom i njegovim toksicnim metabolitom hidrazinom. U tu smo svrhu utvrdili razine reaktivnih kisikovih spoj eva (ROS ), lipidnu peroksidaciju, depolarizaciju mitohondrij a, reducirani glutation (GSH) te oksidirani glutation (GSSG). Izoniazid nije doveo do znacajnoga nastanka ROS-a u normalnih hepatocita, alije zato bio znacajan u stanica osiromasenih glutationom. I izoniazid i hidrazine doveli su do depolarizacije membrane mitohondrija. Hidrazin je smanjio stanicnu rezervu GSH i povecao razinu GSSG. Taurin (200 (xmol L^sup -1^) i N-acetilcistein (200 (xmol L^sup -1^) uspjesno su zastitili od toksicnoga djelovanja izoniazida i/ili hidrazina, smanjivsi nastanak ROS-a, lipidnu peroksidaciju i ostecenje mitohondrija. Taurin je sprijecio potpuni gubitak GSH-a te snizio razine GSSG-a u stanica tretiranih hidrazinom. Rezultati naseg istrazivanje upucuju na to da se zastitno djelovanje taurina od stanicne toksicnosti izoniazida i hidrazina moze pripisati njegovu andioksidacijskome djelovanju.

KLJUCNE RIJECI: citotoksicnost, glutation, lipidna peroksidacija,...

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