Evaluation of the effect of acetyl L-carnitine on experimental cisplatin nephrotoxicity

Objective: To investigate the protective effects of acetyl L-carnitine on cisplatin-induced nephrotoxicity in ratsMaterials and methods: Four different groups of 28 adult female Wistar albino rats were studied. Baseline serum creatinine, 24 hour urine volume and urine creatinine values of all the rats were obtained at the beginning of the study. Rats in the first group were given one hour intraperitoneal infusion of normal saline, rats in the second group were given one hour intraperitoneal infusion of normal saline after subcutaneous injection of acetyl L- carnitine (200mg/kg), rats in the third group were given one hour intraperitoneal infusion of cisplatin (16 mg/kg) , rats in the fourth group were given one hour intraperitoneal infusion of cisplatin (16mg/kg) after subcutaneous injection of acetyl L- carnitine (200mg/kg) . On the second and third days of the study, the second and fourth group were injected with acetyl L-carnitine (200mg/kg) while the first and third group were injected with same doses of normal saline. Following the collection of 24 hour urine samples on the third day, all rats were sacrificed on the fourth day after serum sampling and kidney samples were isolated for histopathological examination with light, immuneflourescent and electron microscopy.Results: Among the four groups; the third day mean serum creatinine values were higher in the cisplatin and cisplatin+acetyl L-carnitine administered groups. On the comparison of these two groups the mean serum creatinine value was higher in the cisplatin administered group. The mean value of total L-carnitine /creatinine in 24- hour urine collected on the third day was lowest in the cisplatin administered group and found to be significantly decreased compared to the control group injected with acetyl L-carnitine. The histopathological examination of the kidney samples of the cisplatin administered group revealed peritubular intersititial cell proliferation, inflammatory cell infiltration, desquamation of proximal tubule cells, tubular thyroidisation, glomerular necrosis and loss of microvilli. On the other hand the findings of proximal tubular desquamation, tubular thyroidisation, glomerular necrosis and loss of microvilli were much more less in the cisplatin+acetyl L-carnitine administered group and there was no evidence of intersititial cell infiltration or inflammatory cell infiltration in this group. Consistent with the light microscopic findings; the electron microscopic examination of the kidney in cisplatin administered group revealed irregular glomerular basement membrane and foot process fusion. There was focal thickening of the glomerular basement membrane in the group administered with cisplatin+ acetyl L-carnitine but the foot processes of podocytes were intact. TUNEL positive apoptotic cell death was higher in the cisplatin and cisplatin+acetyl L-carnitine administered groups. On the comparison of these two groups the apoptotic cell death was significantly higher in the group administered with cisplatin. Caspase 3,8 and 9 activities were higher in the cisplatin administered group compared to cisplatin+acetyl L-carnitine administered group.Conclusion : Antioxidative, antiapoptotic and antiinflammatory properties of acetyl L-carnitine were supported by the findings that the use of this agent improves the kidney function tests and has the effects of tissue protection and inhibition of apoptosis in cisplatin induced nephrotoxicity.Key words: Cisplatin, acetyl L-carnitine, , nephrotoxicity