Safety Assessment of Artemether/Lumefantrine/ Tinidazole on the Kidneys of Healthy and Diseased Mice
Asian Journal of Biology,
Artemether/lumefantrine/tinidazole- (A/L/T) can be use for the treatment of malaria; therefore its safety assessment is imperative. This study assessed its safety on the kidneys of healthy and diseased mice. Fifty four Swiss albino mice were used for this study. Mice were diseased with Plasmodium berghei () and treated with T (28.6 mg/kg), A/L (2.3/13.7mg/kg) and A/L/T for 4 days. Healthy mice were treated with T (28.6 mg/kg), A/L (2.3/13.7mg/kg) and A/L/T for 28 days. At the termination of treatment, the mice were weighed, sacrificed and blood samples were collected and examined for kidney biochemical markers. Kidneys were weighed and evaluated for oxidative stress markers and histology. T, A/L and A/L/T had no significant (p>0.05) effects on all evaluated parameters in diseased mice when compared to control. Body weight was decreased whereas kidney weight was increased in healthy mice treated with T, (p<0.05), A/L (p<0.05) and A/L/T (p<0.01) when compared to control. Significantly elevated serum creatinine, urea, uric acid levels with significantly decreased albumin, and total protein levels occurred in healthy mice treated with T (p<0.05), A/L (p<0.01) and A/L/T (p<0.001) when compared to control. Altered kidney oxidative stress markers characterized by significantly decreased glutathione, catalase, glutathione peroxidase, superoxide dismutase levels with significantly increased malondialdehyde levels occurred in healthy mice treated with T (p<0.05), A/L (p<0.01) and A/L/T (p<0.001) when compared to control. A/L/T produced tubular necrosis and enlarged Bowman’s space in healthy mice. The use of A/L/T as an antimalarial drug may be safe on the kidney, but long term use may cause kidney damage.
How to Cite
Wiwanitkit V. Antimalarial drug and renal toxicity. J Nephropharmacol. 2016;5(1):11-12.
Kane-Gill SL, Goldstein SL. Drug-induced acute kidney injury: a focus on risk assessment for prevention. Crit Care Clin. 2015;31(4):675-84.
Gandhi TK, Burstin HR, Cook EF, et al. Drug complications in outpatients. J Gen Intern Med. 2000;15(3):149-154.
Ehrhardt S, Meyer CG. Artemether–lumefantrine in the treatment of uncomplicated Plasmodium falciparum malaria. Therapeutics and Clinical Risk Management. 2009;5:805–815.
White NH, Breman JG. Malaria. Harrison’s principles of internal medicine. 17th ed. New York: McGraw-Hill. 2008;1280-94.
Stover KR, King ST, Robinson J. Artemether-Lumefantrine: An Option for Malaria the Annals of Pharmacother. 2012; 46:567-577.
World Health Organization (WHO). World malaria report 2014. Geneva: WHO; 2014.
Li Q, Xie LH, Johnson TO, Si Y, Haeberle AS, Weina PJ. Toxicity evaluation of artesunate and artelinate in Plasmodium berghei-infected and uninfected rats. Trans R Soc Trop Med Hyg. 2007;101:104- 12.
Campos SB, Rouch LH, Seguro AC. Effects of sodium artesunate, a new antimalarial drug, on renal function. Kidney Int. 2001;59:1044-51.
Macareo L, Lwin KM, Cheah PY, et al. Triangular test design to evaluate tinidazole in the prevention of Plasmodium vivax relapse. Malar J. 2013;12:173 1-6.
Deye G, Gettayacamin M, Pranee H, Im-erbsin R, Sattabongkot J, Rothstein Y, et al. Use of Rhesus Plasmodium cynomolgi model to screen for anti-hypnozoite activity of pharmaceutical substances. Am J Trop Med Hyg. 2012;86: 931-935.
Sarma P. Tinidazole: A new drug in the treatment of vivax malaria. Curr Ther Res. 1988;43:3.
Georgewill UD, Melford H, Adikwu E. Antiplasmodial activity of artemether-lumefantrine-tinidazole on Plasmodium berghei infected mice The Pharm and Chem Jour. 2021;8(1):107-113.
Sedlak J, Lindsay RH. Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman’seeagent. Anal Biochem. 1968;25:192-205.
Aebi H. Catalase in-vitro. Methods Enzymol. 1984;105:121- 6.
Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra WG. Selenium: Biochemical role as a component of glutathione peroxidase. Sci. 1973;179:588-90.
Sun M, Zigma S. An Improved spectrophotometer assay of superoxide dismutase based on epinephrine antioxidation. Anal Biochem. 1978;90:81-9.
Buege JA, Aust SD. Microsomal lipid peroxidation. Meth Enzymol. 1978;52:302-10.
Das BS. Renal failure in malaria. J Vector Borne Dis. 2008;45:83–97.
Elias Adikwu. Alpha lipic acid attenuates cyclophosphamide-doxorubicin-induced hepatic perturbation in rats. Journal of Marine Medical Science. 2020;22:62-8.
Krstic D, Tomic N, Radosavljevic B, et al. Biochemical markers of renal function. Current Medicinal Chemistry. 2016;23(19): 2018-2040.
Lobo DN. Fluid electrolytes and nutrition. Physiological and clinical aspects. Proc Nutr Soc. 2004;63(3):453-466.
Gowda S, Desai PB, Kulkarni SS, Hull SV, Math AK, Vernekar SN. Markers of renal function tests. N Am J Med Sci. 2010;2(4):170–173.
Yoshikawa T, Naito Y. What Is Oxidative Stress? JMAJ. 2002;45(7):271–276.
Abolaji AO, Eteng MU, Omonua O, Adenrele Y. Influence of coadministration of artemether and lumefantrine on selected plasma biochemical and erythrocyte oxidative stress indices in female Wistar rats. Human & Experimental Toxicology. 2013;32(2):206-215.
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