title: Agmatine protects rat liver from nicotine-induced hepatic damage via antioxidative, antiapoptotic, and antifibrotic pathways.
abstract: Tobacco smoking with its various forms is a global problem with proved hazardous effects to human health. The present work was planned to study the defending role of agmatine (AGM) on hepatic oxidative stress and damage induced by nicotine in rats. Thirty-two rats divided into four groups were employed: control group, nicotine-only group, AGM group, and AGM-nicotine group. Measurements of serum hepatic biochemical markers, lipid profile, and vascular cell adhesion molecule-1 were done. In addition, malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH) activity, and nitrate/nitrite (NOx) levels were estimated in the liver homogenates. Immunohistochemistry for Bax and transforming growth factor beta (TGF-β1) and histopathology of the liver were also included. Data of the study demonstrated that nicotine administration exhibited marked liver deterioration, an increase in liver enzymes, changes in lipid profile, and an elevation in MDA with a decline in levels of SOD, GSH, and NOx (nitrate/nitrite). Also, levels of proapoptotic Bax and profibrotic TGF-β1 showed marked elevation in the liver. AGM treatment to rats in nicotine-only group ameliorated all the previous changes. These findings indicate that AGM could successfully overcome the nicotine-evoked hepatic oxidative stress and tissue injury, apoptosis, and fibrosis.
authors.affiliation: Pharmacology and Toxicology, College of Pharmacy, Taibah University, El-Madinah El-Munawarah, Saudi Arabia.|Faculty of Medicine, Suez Canal University, Ismailia Governorate, Egypt.
authors.forename: Nagla A
authors.initials: NA
authors.lastname: El-Sherbeeny
authors.affiliation: Pharmacology and Toxicology, College of Pharmacy, Taibah University, El-Madinah El-Munawarah, Saudi Arabia.|Faculty of Pharmacy, Mansoura University, Dakahlia Governorate, Egypt.
authors.forename: Manar A
authors.initials: MA
authors.lastname: Nader
authors.affiliation: Department of Anatomy, Faculty of Medicine, Taibah University, El-Madinah El-Munawarah, Saudi Arabia. dr.ghalia.attia2016@gmail.com.|Department of Histology and Cell Biology, Faculty of Medicine, Mansoura University, Mansoura, Egypt. dr.ghalia.attia2016@gmail.com.
authors.forename: Ghalia M
authors.initials: GM
authors.lastname: Attia
authors.affiliation: Pharmacology and Toxicology, College of Pharmacy, Taibah University, El-Madinah El-Munawarah, Saudi Arabia.|Faculty of Medicine, Cairo University, Giza, Egypt.
authors.forename: Hayam
authors.initials: H
authors.lastname: Ateyya
mesh_terms: D000376:Agmatine / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000473:pathology / Q000517:prevention & control*; D019610:Cytoprotection; D005978:Glutathione / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000097:blood / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009538:Nicotine; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D000975:Antioxidants; D051017:Apoptosis Regulatory Proteins; D015415:Biomarkers; D008055:Lipids; C508962:Tgfb1 protein, rat; D053773:Transforming Growth Factor beta1; D009569:Nitric Oxide; D008315:Malondialdehyde; D009538:Nicotine; D000376:Agmatine; D013482:Superoxide Dismutase; D005978:Glutathione
keywords: Agmatine; Liver toxicity; Nicotine; Oxidative damage; TGF-β1