title: Deferoxamine alleviates liver fibrosis induced by CCl4 in rats.
abstract: Several chronic liver diseases can lead to the occurrence of hepatic fibrosis through the accumulation of iron, which causes induction of oxidative stress and consequently activation of fibrogenesis. The present study was designed to investigate the potential antifibrotic and anti-oxidant effects of deferoxamine (DFO), a well-known iron chelator in an experimental rat model of liver injury using carbon tetrachloride (CCl4 ). First, the potential effective dose of DFO was screened against CCl4 -induced acute hepatotoxicity. Then, rats were co-treated with DFO (300 mg/kg, i.p.) for 6 weeks starting from the third week of CCl4 induction of chronic hepatotoxicity. Liver function was assessed in addition to histopathological examination. Furthermore, oxidative stress and fibrosis markers were assessed. It was found that treatment of animals with DFO significantly counteracted the changes in liver function; histopathological lesions and hepatic iron deposition that were induced by CCl4 . DFO also significantly counteracted the CCl4 -induced lipid peroxidation increase and reduction in antioxidant activities of superoxide dismutase and glutathione peroxidase enzymes. In addition, DFO ameliorated significantly liver fibrosis markers including hydroxyproline, collagen accumulation, and the expression of the hepatic stellate cells (HSCs) activation marker; alpha smooth muscle actin and transforming growth factor-beta (TGF-β). Together, these findings indicate that DFO possesses a potent antifibrotic effect due to its antioxidant properties that counteracted oxidative stress and lipid peroxidation and restored antioxidant enzymes activities as well as reducing HSCs activation and fibrogenesis.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt.
authors.forename: Aya
authors.initials: A
authors.lastname: Mohammed
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt.
authors.forename: Ekram N
authors.initials: EN
authors.lastname: Abd Al Haleem
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
authors.forename: Wesam M
authors.initials: WM
authors.lastname: El-Bakly
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.|Department of Pharmacology and Toxicology, Faculty of Pharmacy, Misr International University, Cairo, Egypt.
authors.forename: Ebtehal
authors.initials: E
authors.lastname: El-Demerdash
mesh_terms: D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity*; D003676:Deferoxamine / Q000627:therapeutic use*; D008103:Liver Cirrhosis / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002251:Carbon Tetrachloride; D003676:Deferoxamine
keywords: deferoxamine; iron chelator; liver fibrosis; oxidative stress