title: Rhein protects against acetaminophen-induced hepatic and renal toxicity.
abstract: This study investigated the possible protective effects and mechanism of rhein on Acetaminophen (APAP)-induced hepatotoxicity and nephrotoxicity in rats. Treatment of rats with APAP resulted in severe liver and kidney injuries, as demonstrated by drastic elevation of serum glutamate-pyruvate transaminase (GPT), glutamate-oxaloacetic transaminase (GOT), total bilirubin (TBIL), creatinine (CREA), urea nitrogen (UREA) levels and typical histopathological changes including necrosis, phlogocyte infiltration and fatty degeneration in liver, tubules epithelium swelling and severe vacuolar degeneration in kidney. APAP caused oxidative stress, as evidenced by increased reactive oxygen species (ROS) production, nitric oxide (NO) and malondiadehyde (MDA) levels, together with depleted glutathione (GSH) concentration in the liver and kidney of rats. However, rhein can attenuate APAP-induced hepatotoxicity and nephrotoxicity in a dose-dependent manner. Our results showed that GPT, GOT, UREA and CREA levels and ROS production were reduced dramatically, NO, MDA, GSH contents were restored remarkedly by rhein administration, as compared to the APAP alone treated rats. Moreover, the histopathological damage of liver and kidney were also significantly ameliorated by rhein treatment. These findings suggested that the protective effects of rhein against APAP-induced liver and kidney injuries might result from the amelioration of APAP-induced oxidative stress.
authors.affiliation: Institute of Traditional Chinese Material Medica, People's Liberation Army, Beijing 100039, PR China.
authors.forename: Yan-Ling
authors.initials: YL
authors.lastname: Zhao
authors.forename: Guang-De
authors.initials: GD
authors.lastname: Zhou
authors.forename: Hong-Bo
authors.initials: HB
authors.lastname: Yang
authors.forename: Jia-Bo
authors.initials: JB
authors.lastname: Wang
authors.forename: Li-Mei
authors.initials: LM
authors.lastname: Shan
authors.forename: Rui-Sheng
authors.initials: RS
authors.lastname: Li
authors.forename: Xiao-He
authors.initials: XH
authors.lastname: Xiao
mesh_terms: D000082:Acetaminophen / Q000009:adverse effects*; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000880:Anthraquinones / Q000008:administration & dosage / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D001663:Bilirubin / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy*; D003404:Creatinine / Q000097:blood; D005978:Glutathione / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000188:drug therapy*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D009569:Nitric Oxide / Q000032:analysis / Q000378:metabolism; D009584:Nitrogen / Q000652:urine; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000032:analysis / Q000378:metabolism
chemical_list: D000880:Anthraquinones; D000975:Antioxidants; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D000082:Acetaminophen; D003404:Creatinine; D000410:Alanine Transaminase; D005978:Glutathione; D009584:Nitrogen; D001663:Bilirubin; C020491:rhein