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

Drug Chem Toxicol. 2016;39(2):190-8. doi: 10.3109/01480545.2015.1070170. Epub 2015 Aug 3.

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.

Keywords: Acetaminophen; black tea extract; hepatotoxicity; nephrotoxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetaminophen / toxicity*
  • Acute Kidney Injury / chemically induced
  • Acute Kidney Injury / metabolism
  • Acute Kidney Injury / pathology
  • Acute Kidney Injury / prevention & control*
  • Animals
  • Apoptosis / drug effects
  • Camellia sinensis / chemistry*
  • Catechin / administration & dosage
  • Catechin / analogs & derivatives*
  • Catechin / isolation & purification
  • Catechin / therapeutic use
  • Chemical and Drug Induced Liver Injury / etiology
  • Chemical and Drug Induced Liver Injury / metabolism
  • Chemical and Drug Induced Liver Injury / pathology
  • Chemical and Drug Induced Liver Injury / prevention & control*
  • Flow Cytometry
  • Immunohistochemistry
  • Kidney Function Tests
  • Liver Function Tests
  • Male
  • Mice
  • Plant Leaves / chemistry
  • Polyphenols / administration & dosage
  • Polyphenols / isolation & purification
  • Polyphenols / therapeutic use*

Substances

  • Polyphenols
  • thearubigin
  • Acetaminophen
  • Catechin