title: Thearubigins protect against acetaminophen-induced hepatic and renal injury in mice: biochemical, histopathological, immunohistochemical, and flow cytometry study.
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  CONCLUSIONS
  Thearubigins protected against acetaminophen-induced hepatotoxicity and nephrotoxicity in mice possibly through their antioxidant activity.
authors.affiliation: a Department of Pharmacology .
authors.forename: Hussam A S
authors.initials: HA
authors.lastname: Murad
authors.affiliation: b Department of Pediatrics .
authors.forename: H
authors.initials: H
authors.lastname: Habib
authors.affiliation: c Department of Microbiology , and.
authors.forename: Y
authors.initials: Y
authors.lastname: Kamel
authors.affiliation: d Department of Physiology, Faculty of Medicine , Rabigh, King Abdulaziz University (KAU) , Jeddah , Saudi Arabia .
authors.forename: S
authors.initials: S
authors.lastname: Alsayed
authors.affiliation: e Department of Pathology, Faculty of Medicine , Ain Shams University , Cairo , Egypt , and.
authors.forename: M
authors.initials: M
authors.lastname: Shakweer
authors.affiliation: f Department of Biochemistry, Faculty of Science , KAU , Jeddah , Saudi Arabia.
authors.forename: M
authors.initials: M
authors.lastname: Elshal
mesh_terms: D000082:Acetaminophen / Q000633:toxicity*; D058186:Acute Kidney Injury / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D028241:Camellia sinensis / Q000737:chemistry*; D002392:Catechin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000627:therapeutic use; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D005434:Flow Cytometry; D007150:Immunohistochemistry; D007677:Kidney Function Tests; D008111:Liver Function Tests; D008297:Male; D051379:Mice; D018515:Plant Leaves / Q000737:chemistry; D059808:Polyphenols / Q000008:administration & dosage / Q000302:isolation & purification / Q000627:therapeutic use*
chemical_list: D059808:Polyphenols; C086701:thearubigin; D000082:Acetaminophen; D002392:Catechin
keywords: Acetaminophen; black tea extract; hepatotoxicity; nephrotoxicity