Protective effect of pyrrolidine dithiocarbamate on isoniazid/rifampicin‑induced liver injury in rats.

Abstract

Isoniazid (INH) and rifampicin (RIF) continue to be first line anti‑tuberculosis (TB) drugs. However, the use of these drugs is associated with hepatotoxicity. Nuclear factor‑κB (NF‑κB) plays a crucial role in regulating immunity and inflammation. It has been reported that pyrrolidine dithiocarbamate (PDTC), an inhibitor of NF‑κB, exerts a hepatoprotective effect on acute and chronic liver damage. The aim of the present study was to explore the INH/RIF‑induced protective effects and mechanisms of PDTC on liver injury. Rats were intragastrically administered INH (50\xa0mg/kg/day) and RIF (50\xa0mg/kg/day) daily for 28\xa0days. PDTC (50\xa0mg/kg/day) was intraperitoneally injected 2\xa0h after the co‑administration of INH and RIF to compare liver biochemical indicators in the serum, histopathological damage, NF‑κB activity, oxidative stress, hepatic mRNA expression of tumor necrosis factor (TNF)‑α, bile salt export pump (BSEP), and protein expression of BSEP. It was found that the inhibition of NF‑κB activation by PDTC treatment markedly alleviated liver biochemical and histological injury, decreased oxidative stress and mRNA levels of TNF‑α, and prevented decreases in BSEP mRNA and protein expression induced by the co‑administration of INH and RIF. Collectively, the present data suggested that INH/RIF‑induced liver injury is dependent on the activation of NF‑κB. PDTC exerted a therapeutic effect on INH/RIF‑induced liver injury by increasing BSEP expression, and exhibiting antioxidant and anti‑inflammatory activities.