Protective effect of dexpanthenol against tacrolimus-induced nephrotoxicity in rats

Introduction and Aim: Organ transplantation plays a crucial role in extending life expectancy, but minimizing the risk of organ rejection post-transplant is of vital importance. Tacrolimus, an immunosuppressive agent used for this purpose, has a potent effect but carries a risk of nephrotoxicity at high doses. Although Dexpanthenol, with its antioxidant properties, has the potential to protect kidney function, there are limited studies on its preventive effect against tacrolimus-induced nephrotoxicity. This study aims to investigate the protective effect of dexpanthenol on tacrolimus-induced nephrotoxicity. Materials and Methods: This study was conducted with the approval of Çukurova University Animal Experiments Local Ethics Committee(Approval No: 5, dated 18.09.2023), using 32 male Wistar-Albino rats. The rats were randomly divided into four separate groups, with 6 rats in the control group and 8 rats in each of the other groups. The control group received 0.5 cc of saline solution(SF) once daily; the Tacrolimus(TAK) group received Tacrolimus(0,4 mg/kg) daily; the Dexpanthenol(DEX) group received Dexpanthenol(500 mg/kg) once daily; and the Tacrolimus + Dexpanthenol(DEX-TAK) group received Tacrolimus(0,4 mg/kg) and Dexpanthenol(500 mg/kg) daily, both administered intraperitoneally. Biochemical parameters were analyzed to assess oxidative balance and kidney damage among the groups. Blood samples were collected from the experimental groups at the end of the 14th day. Two pathologists, blinded to the group allocations, examined the kidney tissues stained with hematoxylin-eosin under a light microscope. Statistical analyses were performed using SPSS 20.0 software, and a p-value of <0.05 was considered significant. Results: No significant differences were found between the groups for TAS(p=0.827), TOS(p=0.596), OSI(p=0.575), SOD(p=0.952), and NO(p=0.365) values. However, significant differences were observed in IL-6(p=0.008), CRP(p=0.034), TNF-alpha(p=0.014), TGF-β(p=0.012), MDA(p=0.001), urea(p=0.005), and creatinine(p=0.002) levels. Pathological examination revealed significant findings in Bowman capsule expansion(p<0.001), the presence of mitosis(p=0.005), vasa recta leukocyte infiltration(VRLI)(p=0.006), tubular regeneration(p=0.03), tubular dilation(p=0.005), and tubular necrosis(p=0.026). The only parameter without a significant difference among the groups was interstitial inflammation(p=0.467). Conclusion: This study demonstrated that dexpanthenol has a limited protective effect against the nephrotoxic effects of tacrolimus. Monitoring IL-6 and TGF-beta levels is important for the early detection of kidney graft rejection and fibrosis, and dexpanthenol may have the potential to reduce nephrotoxicity by lowering these levels. However, further research is needed to confirm its efficacy.