Investigation of potential nephroprotective effects of L-carnitine against urugrafin induced nephrotoxicity via TNF-, Cas-3, Bax, Bcl2 and Cas-9 gene expressions

Investigation of the prevention of urografin-induced nephrotoxic effects of L-carnitine through specific pathways against urografin-induced nephrotoxicity in experimental animals. The study was performed with 32 female Wistar Albino rats between 250-350 g obtained from SDU Experimental Animals. The experimental animals were divided into 4 groups with 8 animals in each group: Control group: The group in which no substance was administered. Radiocontrast (RC) group: Group injected with contrast material. RC and L-carnitine (RC + LCR) group: Group injected with contrast agent and L-carnitine. LCR group: LCR injected group. BUN and creatinine values were studied as renal function tests. Kidney tissues were obtained. Histopathologic and immunohistochemical examinations were performed. Pathologic changes such as inflammatory cell migration and hemorrhage were examined. Immunohistochemically, the expression of markers such as TNF-α and Cas-3 were analyzed to evaluate inflammation and apoptosis. Bax, Bcl2, Cas-9 gene expressions, which are mitochondrial stress-related apoptosis indicators, were analyzed by qRT-PCR analysis. Oxidative stress markers were evaluated biochemically in kidney tissue by spectrophotometric method. In the present study, a comparison was made between the RC and RC+LCR groups. The results indicated that the renal damage observed in the RC group was significantly reduced in the RC+LCR group at the histopathologic level. Furthermore, the increase in Cas-3 levels observed in the RC group was significantly decreased in the RC+LCR group. Additionally, TNF-α expression increased in the RC group and decreased significantly in the RC+LCR group. In the context of oxidative stress parameters, a significant decrease was observed in certain parameters when the RC group was compared with the RC+LCR group.The heightened expression levels of Bax and Cas-9 genes in the RC group diminished significantly in the RC+LCR group, and the decline in Bcl2 expression in the RC group exhibited a marked increase in the RC+LCR group.No substantial disparities were identified between the RC and LCR groups with respect to urea and creatinine values. The following conclusions were derived from the experimental investigation. The data obtained from the findings indicated that renal damage detected at histopathologic, genetic, and immunohistochemical levels in the RC group could be prevented by LCR. Keywords: L-carnitine, Contrast Media, Nephrotoxicity, Mitocondrial Stress, Apoptosis