Allicin ameliorates kidney function and urinary bladder sensitivity in cyclosporine A-treated rats

Abstract

<jats:p> 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. </jats:p>

Hydrogen‐rich water alleviates cyclosporine A‐induced nephrotoxicity via the Keap1/Nrf2 signaling pathway

“…Growing evidence has shown that an overproduction of ROS, combined with inefficient antioxidant defenses in response to oxidative stress, is implicated in nephrotoxicity caused by CsA, leading to renal dysfunction (increased UP, BUN, and SC, and decreased CCr). [ 21,26,27 ] Studies have shown that CsA‐induced ROS production mediates renal tubular cell apoptosis, tubulointerstitial fibrosis, and arteriopathy. [ 28 ] Li et al [ 29 ] found that CsA decreased the activity of SOD and GSH, which induced the pathogenesis of renal dysfunction.…”

“…Urine samples were centrifuged for 15 minutes at 3000 rpm for subsequent analysis of urinary protein (UP) and creatinine clearance (CCr). [ 21 ] At the end of the experiment, body weight was recorded and mean arterial pressure (MAP) was measured and analyzed using the BL‐420S biological signal analytical system (Taimeng Technology Co Ltd, Chengdu, China).…”

Nicorandil mitigates folic acid‐induced nephrotoxicity in mice: Role of iNOS and eNOS

“…Ccr (ml/min) = [urinary Cr (mg/dl) × urine volume (ml) x 1440/serum Cr (mg/dl)] 1440: total number of minutes per day. [ 15 ]…”

“…Glomerular filtration was indicated by deducing creatinine clearance (Ccr) by applying the following equation: Ccr (ml/min) = [urinary Cr (mg/dl) × urine volume (ml) x 1440/ serum Cr (mg/dl)] 1440: total number of minutes per day. [15] 2.5 | Determination of antioxidant status MDA was estimated in accordance with the method of Ohkawa et al [16] The principle based upon its reaction with thiobarbituric acid and the obtained color was measured by a spectrophotometer at 532 nm. GSH was evaluated in accordance with the method of Ellman.…”

Effects of esomeprazole and pantoprazole on renal function in stable kidney transplantation recipients: A randomized clinical trial.

“…One of the major sources of intracellular reactive oxygen species in mitochondria. Thus, these organelles are linked to cyclosporin A (CSA) renal toxicity [8].…”