Allicin ameliorates kidney function and urinary bladder sensitivity in cyclosporine A-treated rats.
Cyclosporine-A (CsA) is an immunosuppressive drug which has been used to prevent rejection after organ transplantation and to treat certain autoimmune diseases. However, its therapeutic use is limited by nephrotoxicity. In this study, the modulator effect of allicin on the oxidative nephrotoxicity of CsA in rats was investigated. Furthermore, the effect of allicin on CsA-induced hypersensitivity of urinary bladder rings to acetylcholine (ACh) was estimated. Rats were divided into three groups, control, CsA (15 mg/kg, subcutaneously), and CsA/allicin (50 mg/kg, orally). At the end of the study, all rats were killed and then blood, urine samples, and kidneys were taken. CsA administration caused a severe nephrotoxicity which was evidenced by elevated kidney/body weight ratio, serum creatinine (Cr), blood urea nitrogen, lactate dehydrogenase, and urinary protein with a concomitant reduction in serum albumin and Cr clearance as compared with control. A significant increase in renal contents of malondialdehyde, myeloperoxidase, and tumor necrosis factor-alpha with a significant decrease in renal reduced glutathione, superoxide dismutase activities, and nitric oxide (NOx) content was detected upon CsA administration. Exposure to CsA increased the sensitivity of isolated urinary bladder rings to ACh. Histological analysis revealed that CsA caused tubular necrosis and moderate diffuse tubular atrophy. Allicin protected kidney tissue against the oxidative damage and the nephrotoxic effect of CsA and significantly reduced the responses of isolated bladder rings to ACh. Our study indicates that allicin administration has the potential to protect against CsA-induced renal injury by reducing oxidative stress and inflammation and restoring NOx level.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
D H
DH
El-Kashef
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
A E
AE
El-Kenawi
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
G M
GM
Suddek
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
H A
HA
Salem
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000633:toxicity*; D004220:Disulfides; D005978:Glutathione / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D013441:Sulfinic Acids / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D001743:Urinary Bladder / Q000187:drug effects* / Q000473:pathology / Q000502:physiology
D004220:Disulfides; D007166:Immunosuppressive Agents; D020011:Protective Agents; D013441:Sulfinic Acids; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; C006452:allicin; D016572:Cyclosporine; D003404:Creatinine; D007770:L-Lactate Dehydrogenase; D009195:Peroxidase; D013482:Superoxide Dismutase; D005978:Glutathione; D000109:Acetylcholine
Cyclosporine-A; TNF-α; allicin; nephrotoxicity; nitric oxide; urinary bladder