Protectif effect of calpain inhibition on contrast-induced nephropathy in rats

Contrast-induced nephropathy (CIN) is a complex syndrome of acute renal failure occurring after the use of contrast media and is the third most common cause of acute kidney injury in hospitalized patients. CIN is associated with increased morbidity and mortality, and increased costs of medical care. Although the underlying mechanisms of CIN is unclear, some mechanisms are suspected such as haemodynamic changes of renal blood flow, which lead to hypoxia of the renal medulla, direct toxic effects of contrast media (CM) on renal cells and oxidative stres. It was shown that calpain inhibitor-1 (CAL-1), which has antioxidant and antiapoptotic effects, attenuated the renal ischemia-reperfusion injury. In this study, antioxidant and protective effects of CAL-1 on apoptotic changes of the rat renal tissue in experimental model of CIN were investigated.Twenty-eight Sprague Dawley female rats, aged 8-10 weeks were used. The experimental animals were divided into 4 groups that have 7 animals in each group: control, contrast media (CM), CAL-1 and CAL-1 + CM. No application made to the control group (group 1). Exception of control group, the others was left for 3 days without water. CIN was induced by administration of high-osmolal contrast media diatrizoate (6 ml/kg) after 48 h of dehydration into the tail vein. Rats of CAL-1 and CM + CAL-1 groups were administered Cal I-1 (10 mg/kg, IP) 30 minutes before administration of CM. Kidney function parameters, renal tissue oxidative stress markers were measured. After the experiment rats were decapitated and renal tissues were obtained and dyed with Haematoxylin-Eosin, periodic acid shiff (PAS) and TUNEL paints.Increases of serum creatinine and urea levels in CM group were significantly high than control group (respectively, p<0.002, p<0.002). Serum creatinine and urea levels of CM + CAL-1 group were significantly lower than those in CM group (respectively, p<0.002, p<0.007). Tissue malonyldialdehyde (MDA) levels in CM + CAL-1 group were lower than in CM group. In CM + CAL-1 group catalase (CAT) enzyme activity was higher than the control group but lower than the CM group. Superoxide dismutase (SOD) activity showed no significant difference between the groups.In this study were observed structural changes in glomeruli, mesangial matrix hyperthrophy, increase of infiltrating cells in medulla, tubular dilatation, injury of tubuler epithelium, transparent tubuli with vacuolisation on the renal tissues of CM group rats with PAS staining. But in CM + CAL-1 and CAL-1 group, there were similar histological findings with control group. CM group had a significant increase in apoptotic cells with TUNEL staining. There was a significant reduction in apoptotic cells in CM + CAL-1 group compared to diabetic group.In conclusion, these results showed that oxidative stres and apoptosis have important role in pathogenesis of CIN and CAL-1 has a protective effect against CIN on the basis of the biochemical and pathological findings. The data obtained from this study, should be supported with other clinical and experimental studies.Key Words: Contrast-induced nephropathy (CIN), apoptosis, oxidative stres, calpain inhibitor-1 (CAL-1).