Effects of Dawa-ul-Kurkum, a Unanipolyherbal preparation, in anti-tubercular drug induced hepatotoxicity in rats and its possible mechanisms

Abstract

Anti-tubercular drug therapy is associated with hepatotoxicity which sometimes leads to hospitalization and life-threatening problems. The effects of a polyherbal Unani formulation, Dawa-Ul-Kurkum were evaluated on anti-tubercular (TB) drugs induced hepatotoxicity in rats and its possible mechanisms were investigated. Liver damage was induced in Wistar rats by daily oral administration of a combination of anti-TB drugs for 28 days and the effects of various drug treatments were assessed on morphological, biochemical and histological markers of liver toxicity. In the vehicle treated experimental group, anti-TB drugs induced significant derangements in liver function parameters and histopathological examination showed hepatocyte degeneration, focal necrosis, perivascular infiltration of inflammatory cells and mild vasodilation. Pretreatment with Dawa-Ul-Kurkum (DK) showed marked protective effects against the Anti-TB drugs induced biochemical and histopathological derangements of liver function. Similar effects were also seen after the hydroalcoholic extract of DK (HA), though to a lesser extent. The hepatoprotective effects of DK and HA were comparable to that seen after silymarin therapy. Liver damage induced by Anti-TB drugs was associated with elevated levels of MDA and NOx whereas; GSH levels were reduced, as compared to controls. Pretreatments with DK and HA induced differential degrees of attenuations in these oxidative stress parameters. The results validate the hepatopotective effects of Dawa-Ul-Kurkum in Anti-TB drugs induced hepatotoxicity and suggest that attenuation of oxidative stress by the polyherbal may be the mechanism of action for such effects.