title: Agmatine improves renal function in gentamicin-induced nephrotoxicity in rats.
abstract: The present study was designed to explore the possible protective effects of agmatine, a known nitric oxide (NO) synthase inhibitor, against gentamicin-induced nephrotoxicity in rats. For this purpose, we quantitatively evaluated gentamicin-induced renal structural and functional alterations using histopathological and biochemical approaches. Furthermore, the effect of agmatine on gentamicin-induced hypersensitivity of urinary bladder rings to acetylcholine (ACh) was evaluated. Twenty-four male Wistar albino rats were randomly divided into 3 groups, namely control, gentamicin (100 mg/kg, i.p.), and gentamicin plus agmatine (40 mg/kg, orally). At the end of the study, all rats were sacrificed and then blood and urine samples and kidneys were taken. Administration of agmatine significantly decreased kidney/body mass ratio, serum creatinine, lactate dehydrogenase (LDH), renal malondialdehyde (MDA), myeloperoxidase (MPO), NO, and tumor necrosis factor-alpha (TNF-α) while it significantly increased creatinine clearance and renal superoxide dismutase (SOD) activity when compared with the gentamicin-treated group. Additionally, agmatine ameliorated tissue morphology as evidenced by histological evaluation and reduced the responses of isolated bladder rings to ACh. Our study indicates that agmatine administration with gentamicin attenuates oxidative-stress associated renal injury by reducing oxygen free radicals and lipid peroxidation, restoring NO level and inhibiting inflammatory mediators such as TNF-α.
authors.affiliation: a Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
authors.forename: Dalia H
authors.initials: DH
authors.lastname: El-Kashef
authors.affiliation: a Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
authors.forename: Asmaa E
authors.initials: AE
authors.lastname: El-Kenawi
authors.affiliation: b Urology and Nephrology Center, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt.
authors.forename: Mona
authors.initials: M
authors.lastname: Abdel Rahim
authors.affiliation: a Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
authors.forename: Ghada M
authors.initials: GM
authors.lastname: Suddek
authors.affiliation: a Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
authors.forename: Hatem A
authors.initials: HA
authors.lastname: Salem
mesh_terms: D000376:Agmatine / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D003404:Creatinine / Q000378:metabolism; D005839:Gentamicins / Q000009:adverse effects*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism; D007677:Kidney Function Tests / Q000379:methods; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism
chemical_list: D000975:Antioxidants; D005839:Gentamicins; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D008315:Malondialdehyde; D000376:Agmatine; D003404:Creatinine; D007770:L-Lactate Dehydrogenase; D009195:Peroxidase
keywords: TNF-α; agmatine; gentamicin; gentamycine; nephrotoxicity; nitric oxide; néphrotoxicité; oxyde nitrique; urinary bladder; vessie