In vivo protective effect of protocatechuic acid on tert-butyl hydroperoxide-induced rat hepatotoxicity.
Increasing evidence regarding free-radical generating agents and the inflammatory process suggests that accumulation of reactive oxygen species (ROS) can involve hepatotoxicity. Previously, we found that protocatechuic acid (PCA), a polyphenolic compound from Hibiscus sabdariffa L. possessing free radical-scavenging capacity, protected against oxidative damage induced by tert-butylhydroperoxide (t-BHP) in rat primary hepatocytes. In this study, first PCA was evaluated by its capacity of inhibiting xanthine oxidase (XO) and lipoxygenase (LO) activity in vitro, then it was used to induce hepatotoxicity to assess the antioxidant and anti-inflammatory bioactivity of PCA in vivo. Our investigation showed that pretreatment with PCA (50-100 mg/kg) by gavage for 5 days before a single dose of t-BHP (ip; 0.2 mmol/kg ) significantly lowered serum levels of the hepatic enzyme markers lactate dehydrogenase (LDH) and alanine (ALT) and aspartate (AST) aminotransferase, and reduced oxidative stress of the liver by evaluating malondialdehyde (MDA) and glutathione (GSH). Histopathological evaluation of the rat livers revealed that PCA reduced the incidence of liver lesions, including hepatocyte swelling, leukocyte infiltration, and necrosis induced by t-BHP. In addition, PCA inhibited t-BHP-induced tyrosine phosphorylation, an implication of the activation of a stress signal pathway, in the liver. These results indicate that PCA protects against t-BHP-induced hepatotoxicity by its antioxidant and anti-inflammatory characteristics accompanied by blocking of stress signal transduction.
Liu
Chuen-Lan
CL
Department of Anatomy, College of Medicine, Chung Shan Medical University, No. 110, Sec. 1, Chien Kuo N. Rd., Taichung, 402 Taiwan.
Wang
Jin-Ming
JM
Chu
Chia-Yih
CY
Cheng
Ming-Tzong
MT
Tseng
Tsui-Hwa
TH
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology / Q000517:prevention & control*; D005978:Glutathione / Q000378:metabolism; D062385:Hydroxybenzoates / Q000494:pharmacology*; D007150:Immunohistochemistry; D015227:Lipid Peroxidation / Q000187:drug effects; D008084:Lipoxygenase / Q000378:metabolism; D008099:Liver / Q000473:pathology; D008297:Male; D019660:Malvaceae / Q000737:chemistry; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation; D010946:Plants, Medicinal / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D014969:Xanthine Oxidase / Q000378:metabolism; D020122:tert-Butylhydroperoxide / Q000037:antagonists & inhibitors* / Q000633:toxicity*
D016588:Anticarcinogenic Agents; D062385:Hydroxybenzoates; C009091:protocatechuic acid; D020122:tert-Butylhydroperoxide; D008084:Lipoxygenase; D014969:Xanthine Oxidase; D005978:Glutathione