الفهرس | Only 14 pages are availabe for public view |
Abstract Drug induced liver injury is the most common reason for drug withdrawal from the market, DILI may be predictable (dose dependant) or unpredictable (idiosyncratic). Predictable DILI occurs when an individual is exposed to a toxic level of some drugs or their metabolites, while unpredictable DILI is not dose-dependent and hardly expected by animal models. Recognizing the type and the mechanism of liver injury maybe helpful in identifying the causative agent, so it is challenging to study every suspected agent and design an animal model that can reproduce its toxicity. Since its approval, leflunomide-induced liver injury has been reported in several studies. Although, severe cases of leflunomide-induced liver injury leading to hospitalization are rare, the risk is higher with concurrent liver disease or use of other hepatotoxic drugs. The current study was conducted to investigate the potential protective effects of carvedilol and crocin alone and in combination against leflunomide-induced hepatic injury and to clarify the possible mechanism(s) through which they may elicit their effects. Mice were treated with 1% CMC (10 ml/kg, P.O.; normal control group), leflunomide every two days (10 mg/kg, P.O.; leflunomide group), carvedilol one hour before leflunomide administration (10 mg/kg, P.O.; carvedilol group), crocin daily one hour before the scheduled time for leflunomide administration (20 mg/kg, P.O.; crocin group), or leflunomide + carvedilol + crocin (combination group) for eight weeks. |