Thearubigins protect against acetaminophen-induced hepatic and renal injury in mice: biochemical, histopathological, immunohistochemical, and flow cytometry study

Abstract

Context: Acetaminophen toxicity is used as a model for studying chemical toxicity. N-acetylcysteine (NAC) is used for the treatment of hepatotoxicity; however, there is no specific therapy for nephrotoxicity. Objective: This study was designed to investigate the potential protective effect of black tea extract (BTE) and its main phenolic pigment, thearubigins (TRs), against acetaminophen (APAP)-induced hepatic and renal injury in mice. Materials and methods: Besides control groups, six groups (n = 8) were given intraperitoneally APAP (300 mg/kg) and then after 1.5 hours were treated intraperitoneally as follows: NAC (318 mg/kg), BTE (3%, 4.5%), and TRs (50, 60, and 70 mg/kg). Six hours post-APAP injection, blood was collected for biochemical measurements. Later, liver and kidneys were removed for histopathological, immunohistochemical, and flow cytometry studies. Results: APAP increased alanine aminotransferase and malondialdehyde and decreased glutathione levels in blood. Treatments significantly reversed these changes mostly with NAC and TRs70. TRs showed dose-dependent significant differences. The APAP-induced central lobular hepatic necrosis and increased TUNEL positivity were mild with co-administration of NAC and TRs (60, 70) while moderate with co-administration of BTE (3, 4.5) and TRs50. The APAP-increased serum creatinine level was significantly reversed by treatments (mostly TRs60, 70). The APAP-induced renal tubular epithelial degeneration and necrosis were mild with co-administration of TRs (60, 70) while moderate with co-administration of NAC, BTE (3, 4.5), and TRs50. The APAP-accumulated apoptotic cells in sub-G1 phase were significantly decreased by treatments, mostly by NAC and TRs70 in the liver and TRs (60, 70) in kidneys. Conclusion: Thearubigins protected against acetaminophen-induced hepatotoxicity and nephrotoxicity in mice possibly through their antioxidant activity.