Diacerein protects against thioacetamide-induced acute liver injury via modulating HMGB1/TLR4/MyD88/NF-κB signaling...

Acute liver injury (ALI) is a serious disease which happens suddenly in people with or without previous liver disease. In this experiment, thioacetamide (TAA) was utilized to induce ALI. The experimental design was conducted using forty-eight adult male Sprague-Dawley rats, which were randomly divided into six groups (n = 8 per group). The control group received no treatment, Dia 100 group received diacerein (100 mg/kg, orally) only once daily for six consecutive days, TAA group received a single intraperitoneal injection of TAA at a dose of 500 mg/kg. For the treatment groups, rats were pretreated orally for six days prior to TAA administration; NAC + TAA group received N-acetylcysteine (50 mg/kg), followed by a single intraperitoneal injection of TAA (500 mg/kg) on day 6. Dia 50 + TAA group received diacerein (50 mg/kg) and Dia 100 + TAA group received diacerein (100 mg/kg) for six consecutive days, followed by TAA injection on day 6. Twenty-four hours after TAA administration, all rats were euthanized. Blood samples were collected for serum separation, and liver tissues were harvested for the assessment of biochemical parameters. Pretreatment with diacerein conferred hepatoprotective effects as evidenced by considerable (p ≤ 0.05) decrease in liver enzymes; ALT, AST, ALP, GGT concomitant with profound (p ≤ 0.05) elevation in serum level of albumin besides improvement in hepatic architecture when compared to TAA group. Diacerein also showed antioxidant properties as evidenced by the significant (p ≤ 0.05) decline in MDA content and substantial (p ≤ 0.05) increment in GSH level. Moreover, diacerein markedly (p ≤ 0.05) reduced inflammation by down-regulating HMGB1/TLR4/MYD88/NF-κB signaling pathway. Collectively, diacerein might be a potential therapeutic candidate for treatment of ALI pending further clinical studies to confirm this notion.