Lycopene in the preventability of nephrotoxic effects of cyclosporine A in ischemia/reperfusion injury in rats

Use of high dose cyclosporine disrupts renal hemodynamics and causes renal nephrotoxicity. Thus it causes rejection of allograft and decreases allograft survival. In the current study, it was aimed to investigate whether lycopene, a natural carotenoid, can inhibit nephrotoxic effect of cyclosporin A on kidneys. Materials and Methods: In this study, following right nephrectomy, male Sprague Dawley rats (n=40) were randomly allocated to experimental groups for 30 days as outlined below: Control group (n=10): Olive oil (as carrier) was given intraperitoneally (i.p.) at 0,8 mL/kg per day, Cyclosporine group (n=10): Cyclosporine was injected i.p. at 20 mg/kg per day as a single dosis Cyclosporine A + Lycopene group (n=10): Cylcosporine and Lycopene were injected i.p. at 25 mg/kg and 20 mg/kg per day, respectively. Lycopene group (n=10): Lycopene was injected i.p. at 25 mg/kg per day. Following completion of above injection protocol, buldog clamps were placed on the left renal arteries in all epxerimental animals and renal arterial ischemia was continued for 30 minutes. Afterwards reperfussion was ensued and surgical procedure was completed. The animals were decapitated one week after renal ischemia-reperfussion. The upper halves of the kidneys were stored at -80 C for enzyme analyses, whereas lower halves were kept in 10 % formaldehyde solution for histopathological examination. Results: Accumulation of eosinophilic substances in tubuls, narrowing in Bowman capsule, atrophy, necrosis and dilatation of tubules and fibrosis in the interstitiel were observed. These lesions were partially improved following lycopene administration. Statistically significant differences were detected among serum Cl- levels of the experimental groups (p<0.008). Serum cholesterol levels in groups given lycopene and cyclosporin+lycopene were found to be higher compared to other groups (P<0,004). Serum Na+ levels of cyclosporin A + lycopene group was also higher compared to other groups whereas K+ levels in lycopene group was determined to be increased in comparison to other groups. Cyclosporin A as well as cylosporin A + lycopene administrations were associated with increased serum cretainine concentration (P=0.0047). Cyclosporin injection elevated lipid peroxidation level (as TBARS) in kidney tissues (P<0,0003). Conclusion: Cylosporine A causes nephrotoxicity by increasing lipid peroxidation and by disrupting tubuler function, and these negative effects were ameliorated by the use of lycopene