Abstract
Objective: In this study, we aimed to investigate the cytoprotective effect of L-carnitine against cisplatin-induced nephrotoxicity and to compare its efficacy with that of amifostin by quantitative renal Tc 99m DMSA uptake. Material and Methods: Male Wistar rats were randomly divided into six groups of six animals each. 1) Control (saline; 5 ml/kg intraperitoneally); 2) L-carnitine (CAR; 300 mg/kg intraperitoneally); 3) Amifostine (AMI; 200 mg /kg intraperitoneally); 4) Cisplatin (CIS;7 mg/kg intraperitoneally); 5) Cisplatin plus L-carnitine (CIS + CAR); 6) Cisplatin plus amifostine (CIS + AMI). L-carnitine and amifostine were injected 30 minutes before cisplatin in Group 5 and 6. Tc 99m DMSA, 7.4 MBq/0.2 ml, was injected through the tail vein 72 hours after the drug administration. Rats were killed and kidneys removed by dissection 2 hours after the injection of the radiopharmaceutical. The percentage of the injected dose per gram of kidney tissue (%ID/g) was calculated. Renal function was monitored by measuring BUN and plasma levels of creatinine. Lipid peroxidation and glutathione content were determined by measuring malondialdehyde (MDA) and reduced glutathione (GSH) in kidney tissue homogenates. Results: Tc 99m DMSA uptake per gram tissue of the kidney as %ID/g was 29.54±4.72, 29.86 ± 7.47 and 26.37 ± 4.54 in the control, CAR and AMI groups respectively. %ID/g was the lowest of all the groups, 11.60±3.59 (p<0.01), in the cisplatin group. Carnitine or amifostine administration 30 minutes before cisplatin injection resulted a significant increase in %ID/g, 21.28±7.73 and 18.97±3.24 respectively, compared to those of cisplatin-treated rats (p<0.002). A marked increase in plasma BUN and creatinine indicating nephrotoxicity and acute renal failure was observed in the cisplatin-treated group. MDA and GSH levels were concordant with cisplatin-induced oxidative stress in the kidney tissue.Conclusion: The results showed that L-carnitine significantly attenuates the cisplatin-induced nephrotoxicity as amifostin.Conflict of interest:None declared.
Highlights
Cisplatin is an antineoplastic agent in the treatment of many types of human tumors including testicular, head and neck, ovarian, cervical, nonsmall cell lung carcinoma
We aimed to investigate the role of L-carnitine in the protection of cisplatin-induced nephrotoxicity and to compare its efficacy with that of cytoprotective agent amifostin by using quantitative Tc 99m DMSA uptake measurements and biochemical parameters
Intraperitoneal injection of cisplatin at a single dose of 7 mg/kg body weight resulted in acute renal failure as indicated by significant increase in plasma blood urea nitrogen (BUN) and creatinine levels compared with controls (p
Summary
Cisplatin is an antineoplastic agent in the treatment of many types of human tumors including testicular, head and neck, ovarian, cervical, nonsmall cell lung carcinoma. Its cytotoxic activity is mediated through DNA inter and intrastrand cross linking and adduct formation resulting in defective DNA templates and arrest of DNA synthesis and replication [1] Cisplatin induces significant ototoxicity, neurotoxicity and nephrotoxicity. The side effects of cisplatin, dose-related nephrotoxicity, have been the major factor that restricts its optimal use in cancer therapy. Nephrotoxicity was observed in almost one-third of patients undergoing cisplatin treatment. The precise molecular mechanism of cisplatin nephrotoxicity is not known, recent research reveals that it is a complex multifactorial process involving necrosis, apoptosis, inflammation, ischemia and oxidative stress. Numerous agents have been tested to prevent cisplatin-induced nephrotoxicity [2,3,4] effective methods for clinical use has not been established yet
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