Nephroprotective Potential of Alpha Lipoic Acid in 5-Fluorouracil-Induced Toxicity of Wistar Rats
doi.org/10.26538/tjnpr/v4i12.17
Keywords:
Wistar rats, Kidney, 5-Fluorouracil, Alpha Lipoic AcidAbstract
5-Fluorouracil is a widely used anticancer drug but its therapeutic potential is limited due to its nephrotoxic and hepatotoxic side effects. This study was therefore designed to study the protective effects of Alpha Lipoic Acid (ALA) in 5-Fluorouracil-induced nephrotic damage in Wistar rats. Intraperitoneal injection of 50 mgkg-1 of 5-FU was associated with significant (p ≤ 0.05) increases in the urea, uric acid, creatinine, and potassium levels. However, intraperitoneal injection of 50 mgkg-1 of 5-FU was associated with significant (p ≤ 0.05) decrease in the sodium and magnesium levels in the toxicity model control when compared with untreated control rats. Pretreatment and posttreatment with ALA attenuated these changes. This is indicative of the nephroprotective potential of ALA in 5-FUinduced kidney injury.
References
Ali B, Al-Wabel NA, Shams S, Ahamad A, Khan SA, Anwar Moon A, Sun YK. Drug-Induced Nephrotoxicity and Its Biomarkers. Biomol Ther (Seoul) 2012; 20(3):268- 272.
Afolabi, OK, Adeleke GE, Ugbaja RN. Crocin Alleviates 5-Fluorouracil-induced Hepatotoxicity through the abrogation of Oxidative Stress in Male Wistar rats. Asian Pac J Health Sci. 2016; 3(2):58-68.
Gelen V, Şengül E, Yıldırım S, Atila G. The protective effects of naringin against 5-fluorouracil-induced hepatotoxicity and nephrotoxicity in rats. Iran J Basic Med Sci. 2018; 21:404-410.
Shay KP, Moreau RF, Smith EJ, Smith AR, Hagen TM. Alpha lipoic acid as a dietary supplement: Molecular mechanisms and therapeutic potential. Biochimica et Biophysica Acta. 2009; 1790:1149-1160.
Castro MC, Massa ML, Schinella G, Gagliardino J, Francini F. Lipoic acid prevents livermetabolic changes induced by administration of a fructose-rich diet. J Biochem Biophys Acta. 2013; 1830:2226-2232.
Al-Asmari AK, Khan AQ, Al-Masri N. Mitigation of 5- fluorouracil-induced liver damage in rats by vitamin C via targeting redox-sensitive transcription factors. Hum Exp Toxicol. 2016; 35:1203-1213.
Abdou RH and Abdel-Daim MM. Alpha-lipoic acid improves acute deltamethrin-induced toxicity in rats. Can. J Physiol Pharmacol. 2014; 92(9):773-779.
Fawcett JK and Scott JE. A rapid and precise method for the determination of urea. J Clin Pathol. 1960; 13:156-159.
Bartels H, Bohnzer M, Heierli C. Serum creatinine determination without protein precipitation. Clin Chem Acta. 1972; 37:193-197.
Pileggi VJ, DiGiorgio J,,Wybenga DR. A one-tube serum uric acid method using phosphotungstic acid as protein precipitant and color reagent. Clin Chim Acta. 1972; 37:141.
Kokko JP and Tannen RL. Fluids, Electrolytes. WB Saunders Co, Philadelphia. Lin CC, Hsu CH, Huang CY, Cheng AL, Chen J, Vogelzang NJ, Pu YS. Weekly cisplatin plus infusional high-dose 5-fluorouracil and leucovorin (P-HDFL) for metastatic urothelial carcinoma: an effective regimen with low toxicity. Cancer 2006; 106:1269-1275.
Ajith TA, Abhishek G, Roshny D, Sudheesh NP. Cosupplementation of single and multi doses of vitamins C and E ameliorates cisplatin-induced acute renal failure in mice. Exp Toxicol Pathol. 2009; 61(6):565-571.
Rashid S, Ali N, Nafees S, Hasan SK, Sultana S. Mitigation of 5-Fluorouracil induced renal toxicity by chrysin via targeting oxidative stress and apoptosis in Wistar rats. Food Chem Toxicol. 2014; 66:185-193.
Rashid S, Ali N, Nafees S, Ahmad ST, Hasan SK, Sultana S. Abrogation of 5-flourouracil induced renal toxicity by bee propolis via targeting oxidative stress and inflammation in Wistar rats. J Pharm Res. 2013; 7:189- 194.
Ajeniyi SA and Solomon RJ. Urea and creatinine of Clarias gariepinus in three different commercial ponds. J Nat Sci. 2014; 12:124-138.
Kaya-Dagistanli F, Tanriverdi A, Altinok S, Ozyazgan OM. The effects of alpha lipoicacid on liver cells damages and apoptosis induced by polyunsaturated fatty acids. Food Chem Toxicol. 2013; 53:84-93.
Moini H, Packer L, Saris NE. Antioxidant and prooxidant activities of alpha-lipoic acid and dihydrolipoic acid. Toxicol Appl Pharmacol. 2002; 182(1):84-90.
Wollin SD and Jones PJ. Alpha-lipoic acid and cardiovascular disease. J Nutr. 2003; 133(11):3327-3330.
Kwiecien B, Dudek M, Bilska-Wilkosz A, Knutelska J, Bednarski M, Kwiecien I. In vivo anti-inflammatory activity of lipoic acid derivatives in mice, Postepy. Hig Med Dosw. 2013; 24:331-338.
Packer L, Kraemer K, Rimbach G. Molecular aspects of lipoic acid in the prevention of diabetes complications. Nutr. 2001; 17:888-895.
Anandakumar PP, Malarkodi SP, Sivaprasad TR, Saravanan GD. Antioxidant DL alpha lipoic acid as an attenuator of Adriamycin-induced hepatotoxicity in rat model. Indian J Exp Biol. 2007; 45:1045-1049.
Tsitsimpikou C, Tzatzarakis M, Fragkiadaki P, Kovatsi L, Stivaktakis P, Kalogeraki A, Kouretas D, Tsatsakis AM. Histopathological lesions, oxidative stress and genotoxic effects in liver and kidneys following long term exposure of rabbits to diazinon and propoxur.
Toxicol. 2013; 307:109-114.
Abidemi JA, Gabriel OO, Kennedy IA, Dhirendra S, Daniel DO. Protective effect of carvedilol alone and coadministered with diltiazem and prednisolone on doxorubicin and 5-fluorouracil-induced hepatotoxicity and nephrotoxicity in rats. Pharmacol Res Perspect. 2017; 6(1):00381.
Hak HNGE, Tarek ISM, Gamal AA. “Histological study of the effect of chemotherapy with 5-Fluorouracil on normal liver and kidney of mice. Int J Novel Res Life Sci. 2015; 2:8-13.
Gelen V, Şengül E, Gedikli S, Atila G, Uslu H, Makav M. The protective effect of rutin and quercetin on 5-FUinduced hepatotoxicity in rats. Asian Pac J Trop Biomed. 2017; 7:647-653.
Published
How to Cite
Issue
Section
License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
