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Hepatoprotective effect of Liv. 52 on antitubercular drug-induced hepatotoxicity in rats

1998; Elsevier BV; Volume: 69; Issue: 6 Linguagem: Inglês

1873-6971

V. Vijaya Padma, V. Suja, C. S. Shyamala Devi, Prema,

Pharmacogenetics and Drug Metabolism

SUMMARY Liv.52, a polyherbal Ayurvedic formulation, exhibited hepatoprotective function when tested against chronic antitubercular drug treated rats. Suppression of GSH and antioxidant enzymes (superoxide dismutase, catalase, GPX and GST) were noticed in the liver of antitubercular drug treated animals, accompanied with an increased production of lipid peroxides. Liv.52 afforded hepatoprotection by inhibiting lipid peroxide production and, as a result, the animals showed improved antioxidant status. Drug - induced hepatotoxicity is a potentially serious adverse effect of the currently used antitubercular chemotherapeutic regimens containing isoniazed (INH), rifampicin and pyrazinamide 1-3 . Adverse effects of antitubercular therapy are sometimes potentiated by multiple drug regimen. Thus, though INH, rifampicin and pyrazinamide each in itself are potentially hepatotoxic, when given in combination their toxic effect is enhanced. The conversion of monoacetyl hydrazine, a metabolite of INH, to a toxic metabolite via cytochrome P450 leads to hepatotoxicity. Patients on concurrent rifampicin therapy have an increased incident of hepatitis. This has been postulated to be due to rifampicin-induced cytochrome P450 enzyme-induction, causing an increased production of toxic metabolites from acetyl hydrazine (AcHz) 4 . Other investigators demonstrated that rifampicin increases the metabolism of INH to isonicotinic acid and hydrazine, both of which are hepatotoxic 5 . The plasma half life of AcHz (metabolite of INH) is shortened by rifampicin and AcHz is quickly converted to its active metabolites by increasing the oxidative elimination rate of AcHz, which is related to the higher incidence of liver necrosis caused by INH and rifampicin in combination 6 . Rifampicin induction of the hydrolysis pathway of INH metabolism into the hepatotoxic metabolite hydrazine was reported by Askgaard et al. 7 Pharmacokinetic interaction exists between rifampicin and pyrazinamide in tuberculotic patients, when these drugs are administered concomitantly. Pyrazinamide decreases blood levels of rifampicin by decreasing its bioavailability and increasing its clearance 8 . Pyrazinamide, in combination with INH and rifampicin, appears to be associated with an increased incidence of hepatotoxicity 9 .