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.

• Acetaminophen
• black tea extract
• hepatotoxicity
• nephrotoxicity

Declaration of interest

The authors report no declarations of interest. This project was funded by the Deanship of Scientific Research (DSR), King Abdulaziz University (KAU), Jeddah, under grant number (168/828/1434). The authors, therefore, acknowledge with thanks DSR for technical and financial support.