title: Experimental evidence for the therapeutic potential of tempol in the treatment of acute liver injury.
abstract: Oxidative stress is one of the mechanisms involved in the acute carbon tetrachloride (CCl4)-induced hepatotoxicity. Since 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl, known as tempol, has powerful antioxidant properties, we investigated its potential hepatoprotective effects and the underlying mechanisms that may add further benefits for its clinical usefulness using an acute model of CCl4-induced hepatotoxicity. One hour after CCl4 induction of acute hepatotoxicity, mice were treated with a daily dose of 20 mg/kg/day tempol for 3 days. It was found that treatment of animals with tempol significantly negated the pathological changes in liver function parameters as well as histology induced by CCl4. In addition, tempol significantly ameliorated CCl4-induced lipid peroxidation and GSH depletion, and improved catalase activity. Furthermore, tempol alleviated the inflammation induced by CCl4 as indicated by reducing the liver expression level of nuclear factor-kappa B (NF-κB) and tumor necrosis factor-α (TNF-α). Finally, tempol significantly reduced expression level of the B-cell lymphoma-2 protein (Bcl-2) and active caspase-3 which are known markers of apoptosis. In conclusion, the present study provides important evidences for the promising hepatoprotective effects of tempol that can be explained by amelioration of oxidative stress mainly through replenishment of GSH, restoration of antioxidant enzyme activities, and reduction of lipid peroxides alongside its anti-inflammatory properties.
authors.affiliation: Departments of Pharmacology and Toxicology, College of Pharmacy, Taibah University, Medina, Kingdom of Saudi Arabia. m_meky2001@yahoo.com.|Department of Biochemistry, Faculty of Pharmacy, Minia University, Minia, Egypt. m_meky2001@yahoo.com.
authors.forename: Mekky M
authors.identifier: http://orcid.org/0000-0001-5309-3552
authors.initials: MM
authors.lastname: Abouzied
authors.affiliation: Departments of Pharmacology and Toxicology, College of Pharmacy, Taibah University, Medina, Kingdom of Saudi Arabia.
authors.forename: Heba M
authors.initials: HM
authors.lastname: Eltahir
authors.affiliation: Department of Pharmacology & Toxicology, Faculty of Pharmacy, Minia University, Minia, Egypt.
authors.forename: Ashraf
authors.initials: A
authors.lastname: Taye
authors.affiliation: Department of Pharmacology & Toxicology, Faculty of Medicine, Assiut University, Assiut, Egypt.
authors.forename: Mahran S
authors.initials: MS
authors.lastname: Abdelrahman
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002252:Carbon Tetrachloride Poisoning / Q000150:complications; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D003497:Cyclic N-Oxides / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D013113:Spin Labels
chemical_list: D015415:Biomarkers; D003497:Cyclic N-Oxides; D013113:Spin Labels; C001803:tempol
keywords: Carbon tetrachloride; Hepatotoxicity; Oxidative stress; Tempol