title: Comparative study of antifibrotic activity of some magnesium-containing supplements on experimental liver toxicity. Molecular study.
abstract: BACKGROUND
  Liver fibrosis is the excessive accumulation of extracellular matrix (ECM) proteins including collagen that occurs in most types of chronic liver diseases. This study aimed to investigate and compare the therapeutic efficacy of different magnesium (Mg)-containing supplements (formulations A, B, and C) on carbon tetrachloride (CCl4)-induced liver fibrosis in rats.
  
  
  METHODS
  Liver fibrosis was induced by intraperitoneal injection of rats with CCl4(1:1 in olive oil, 2 mL/kg, three times/week) for 4 weeks, and then rats were orally treated with different Mg-containing supplements (formulations A, B, and C) once daily for another one month. Liver fibrosis was quantified by evaluation of expressions of Collagen I, transforming growth factor β-1 (TGFβ1), platelet-derived growth factor-C (PDGF-C), nuclear factor kappa-β (NF-κβ), and measurement of hepatic collagen (hydroxyproline) level. Also, malondialdehyde (MDA), nitric oxide (NO), glutathione (GSH) level, superoxide dismutase (SOD), and glutathione-S-transferase (GST) activities were estimated.
  
  
  RESULTS
  CCl4administration significantly elevated expressions of the studied genes, hepatic hydroxyproline, MDA, and NO levels and caused depletion of GSH level, decreased SOD, and GST activities when compared with those of their corresponding control, p < 0.05. All magnesium supplements significantly inhibited expressions of the studied genes and attenuated the hepatic hydroxyproline level as compared with those of CCl4-treated group;p < 0.05; for NF-κβ, the highest inhibition was by formulations B and C. Regarding Collagen I, TGFβ1, and hepatic hydroxyproline content, the highest inhibition was by Formulation C, and Formulation A revealed highest inhibition for PDGF-C. All magnesium supplements revealed normalization of oxidant and antioxidants parameters. Histopathological examination supports the biochemical and molecular findings.
  
  
  CONCLUSIONS
  Mg supplements were effective in the treatment of hepatic CCl4-induced fibrosis-rat model.
authors.affiliation: a National Organization for Drug Control & Research , Cairo , Egypt.
authors.forename: Walid Hamdy
authors.initials: WH
authors.lastname: El-Tantawy
authors.affiliation: b Unit of Biochemistry and Molecular Biology, Department of Medical Biochemistry , Faculty of Medicine, Cairo University , Cairo , Egypt , and.
authors.forename: Dina
authors.initials: D
authors.lastname: Sabry
authors.affiliation: c Department of Pharmacology and Toxicology , Faculty of Pharmacy for Girls, Al-Azhar University , Cairo , Egypt.
authors.forename: Ekram Nemr
authors.initials: EN
authors.lastname: Abd Al Haleem
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood; D002251:Carbon Tetrachloride / Q000633:toxicity; D019587:Dietary Supplements; D005260:Female; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008111:Liver Function Tests; D008274:Magnesium / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D016328:NF-kappa B / Q000235:genetics; D009569:Nitric Oxide / Q000096:biosynthesis; D009929:Organ Size / Q000187:drug effects; D017208:Rats, Wistar; D053773:Transforming Growth Factor beta1 / Q000235:genetics
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D016328:NF-kappa B; D053773:Transforming Growth Factor beta1; D009569:Nitric Oxide; D002251:Carbon Tetrachloride; D008274:Magnesium
keywords: Liver fibrosis; Magnesium; PDGF-C; TGFβ1; carbon tetrachloride