title: Protective effect of allicin against gentamicin-induced nephrotoxicity in rats.
abstract: In this study, the modulator effect of allicin on the oxidative nephrotoxicity of gentamicin in the kidneys of rats was investigated by determining indices of lipid peroxidation and the activities of antioxidant enzymes, as well as by histological analyses. Furthermore, the effect of allicin on gentamicin induced hypersensitivity of urinary bladder rings to ACh was estimated. Twenty-four male Wistar albino rats were randomly divided into three groups, control, gentamicin (100mg/kg, i.p.) and gentamicin+allicin (50mg/kg, orally). At the end of the study, all rats were sacrificed and then urine, blood samples and kidneys were taken. Gentamicin administration caused a severe nephrotoxicity as evidenced by an elevated kidney/body weight ratio, serum creatinine, blood urea nitrogen (BUN), serum lactate dehydrogenase (LDH) and proteinuria with a reduction in serum albumin and creatinine clearance as compared with control group. In addition, a significant increase in renal contents of malondialdehyde (MDA), myeloperoxidase (MPO), nitric oxide (NOx) and tumor necrosis factor-alpha (TNF-α) concomitantly with a significant decrease in renal reduced glutathione (GSH) and superoxide dismutase (SOD) activities was detected upon gentamicin injection. Exposure to gentamicin increased the sensitivity of isolated urinary bladder rings to ACh and induced acute renal tubular epithelial cells necrosis. Administration of allicin significantly decreased kidney/body weight ratio, serum creatinine, LDH, renal MDA, MPO, NOx and TNF-α while it significantly increased creatinine clearance, renal GSH content and renal SOD activity when compared to gentamicin-treated group. Additionally, allicin significantly reduced the responses of isolated bladder rings to ACh and ameliorated tissue morphology as evidenced by histological evaluation. Our study indicates that allicin exerted protection against structural and functional damage induced by gentamicin possibly due to its antioxidant, anti-inflammatory and immunomodulatory properties in addition to its ability to retaining nitric oxide level.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
authors.forename: Dalia H
authors.initials: DH
authors.lastname: El-Kashef
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
authors.forename: Asmaa E
authors.initials: AE
authors.lastname: El-Kenawi
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt. Electronic address: ghmsuddek@yahoo.com.
authors.forename: Ghada M
authors.initials: GM
authors.lastname: Suddek
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
authors.forename: Hatem A
authors.initials: HA
authors.lastname: Salem
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D004220:Disulfides; D005786:Gene Expression Regulation / Q000187:drug effects; D005839:Gentamicins / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000517:prevention & control; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D009929:Organ Size; D009195:Peroxidase / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000633:toxicity*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013441:Sulfinic Acids / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D001743:Urinary Bladder / Q000187:drug effects / Q000502:physiology
chemical_list: D000975:Antioxidants; D004220:Disulfides; D005839:Gentamicins; D011500:Protein Synthesis Inhibitors; D013441:Sulfinic Acids; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; C006452:allicin; D007770:L-Lactate Dehydrogenase; D009195:Peroxidase
keywords: Allicin; Gentamicin; Nephrotoxicity; Nitric oxide; TNF-α; Urinary bladder