title: Caffeic acid, a phyto polyphenol mitigates fluoride induced hepatotoxicity in rats: A possible mechanism.
abstract: Fluoride induced hepatotoxicity has been extensively studied in both humans and animals. However, the mechanism underlying in the hepatotoxicity of experimental fluorosis remains obscure. The severity of fluoride toxicity was reduced by oral administration of certain plant derived antioxidants. Caffeic acid (CA) a polyphenolic compound has diverse range of pharmacological activity in the biological system. Therefore, the present study was aimed to investigate the protective mechanism of CA, against fluoride induced hepatotoxicity in rats. The rats were treated with 300 ppm of NaF via drinking water ad libitum alone and in combination with CA at a dose of 50 mg/kg daily for 30 days by oral intubation. CA treatment significantly prevented fluoride induced hepatic damage as evident from the histopathological studies and declined levels of serum fluoride and liver marker enzymes. A significant decrease in the levels of enzymatic (SOD2, CAT, GPx, and GSTpi class) and nonenzymatic (GSH and Vitamin C) antioxidants along with increased ROS, lipid peroxidation, protein carbonyl content, and nitrate levels by fluoride were also prevented in these groups. In addition, CA inhibits fluoride induced apoptosis by altering the Bax and caspase-3p20 expressions. Further, fluoride induced upregulation of Nox4, p38α MAPK, Hsp60, and downregulation of Hsp27 are the indicators for the detection of oxidative damage, apoptosis, and mitochondrial stress was also modulated by CA. These findings reveal that CA supplementation has a protective effect against fluoride induced hepatotoxicity in rats.
authors.affiliation: Molecular Toxicology Laboratory, Department of Biotechnology, Bharathiar University, Coimbatore, Tamilnadu, 641 046, India.
authors.forename: Vishnu Vignesh
authors.initials: VV
authors.lastname: Kanagaraj
authors.forename: Lakshmikanthan
authors.initials: L
authors.lastname: Panneerselvam
authors.forename: Vimal
authors.initials: V
authors.lastname: Govindarajan
authors.forename: Jaishabanu
authors.initials: J
authors.lastname: Ameeramja
authors.forename: Ekambaram
authors.initials: E
authors.lastname: Perumal
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001205:Ascorbic Acid / Q000378:metabolism; D002109:Caffeic Acids / Q000494:pharmacology*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D005786:Gene Expression Regulation; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D050050:Protein Carbonylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D012969:Sodium Fluoride / Q000037:antagonists & inhibitors* / Q000633:toxicity; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D000099156:Superoxide Dismutase 2
chemical_list: D000975:Antioxidants; D001205:Ascorbic Acid; D002109:Caffeic Acids; D053148:Caspase 3; D002374:Catalase; D005978:Glutathione; D005979:Glutathione Peroxidase; D005982:Glutathione Transferase; D006360:Heat-Shock Proteins; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; D017382:Reactive Oxygen Species; D012969:Sodium Fluoride; D013482:Superoxide Dismutase; D051028:bcl-2-Associated X Protein; D048051:p38 Mitogen-Activated Protein Kinases; D000099156:Superoxide Dismutase 2; C494828:Bax protein, rat; C498911:Nox4 protein, rat; C040048:caffeic acid
keywords: Nox4; apoptosis; caffeic acid; fluoride; heat shock proteins; hepatotoxicity