PROTECTIVE EFFECT OF MORINGA OLEIFERA SEED EXTRACT ON CISPLATIN INDUCED NEPHROTOXICITY IN RATS
Keywords:Cisplatin, Moringa Oleifera, Oxidative stress, Nephrotoxicity, Cytokines
Objective: The main objective of this study is to investigate the antioxidant and nephroprotective efficacy of moringa oleifera seed extract (MOSE) against cisplatin which induced acute renal injury.
Methods: Forty male Wister rats were equally segregated into 4 groups (10 rats per group): group I (0.5 ml of sterile saline orally), group II (200 mg MOSE/kg b. wt orally for 10 consecutive days), group III (7.5 mg cisplatin/kg b. wt/intraperitonially as a single dose on the 5th day of the experiment) and group IV (200 mg moringa oleifera seed extract (MOSE)/kg orally for 10 d followed by 7.5 mg cisplatin/kg body weight/intraperitonially once as a single dose on the 5th day of the experiment. Serum biochemical analysis of renal biomarkers (urea, uric acid, and creatinine), oxidative stress markers (malondialdehyde [MDA]), a crucial antioxidant enzyme (catalase) and the expression of renal activity interleukin (IL)-6, (IL)-10 and Tumer necrotic factor (TNF-α) mRNA were determined. Histopathological examination of renal tissue was done.
Results: Cisplatin induced renal damage, increased renal biomarkers (urea, creatinine and uric acid)(375.87±1.65, 5.238±0.25, 4.47±0.25). Tissue concentrations of malondialdehyde, IL-6 and TNF-α.(387.56±0.97, 2.188±0.20, 3.06±0.27)compared to control group(140.58±1.25,0.938±0.017, 1.24±0.17), (163.99±1.34, 1.008±0.05, 0.982±0.026) Moreover, cisplatin induced significantly down-regulation of anti-inflammatory (IL-10) and catalase (0.780±0.47, 1.62±0.06) compared to control one (1.010±0.02, 3.12±0.11),. The histopathological examination showed renal tissue damage and degeneration of tubules in the cortical portion in cisplatin group. However, interestingly concurrent adminsteration of the MOSE with cisplatin can alleviated the renal damage, oxidative stress and renal toxicity caused by cisplatin.
Conclusion: These results suggest that the antioxidant and the anti-inflammatory effects of MOSE alleviate the cisplatin-induced nephrotoxicity.
Dasari S, Tchounwou PB. Cisplatin in cancer therapy: molecular mechanisms of action. Eur J Pharmacol 2014;740:364-78.
Dugbartey GJ, Peppone LJ, Graaf IAM. An integrative view of cisplatin-induced renal and cardiac toxicities: molecular mechanisms, current treatment challenges and potential protective measures. Toxicology 2016;37:158-66.
Sameeh AM, Reham IM, Amina RA, Abdel Razik HF. The protective effect of moringa tea against cypermethrin-induced hepatorenal dysfunction, oxidative stress, and histopathological alterations in female rats. Asian J Pharm Clin Res 2018;11:111-7.
Kou X, Li B, Olayanju J, Drake J, Chen N. Nutraceutical or pharmacological potential of Moringa oleifera Lam. Nutrients 2018;10:343.
Khalil SR, Abdel Motal SM, Abd-Elsalam M, El-Hameed NEA, Awad A. Restoring strategy of ethanolic extract of Moringa oleifera leaves against Tilmicosin-induced cardiac injury in rats: targeting cell apoptosis-mediated pathways. Gene 2020;730:144272.
Harborne JB. Phytochemical methods a guide to modern techniques of plant analysis; 1973.
Purena R, Seth R, Bhatt R. Protective role of emblica officinalis hydro-ethanolic leaf extract in cisplatin induced nephrotoxicity in rats. Toxicol Rep 2018;5:270–7.
Boorla SK, Panchagiri S, Shastrala KK, Bonagiri R, Vangala M. Evaluation of role of atorvastatin in cisplatin induced nephrotoxicity in wistar rats. Glob J Pharmacol 2014;8:279-83.
Murray R Creatinine, Kaplan A. Clin Chem The C. V. Mos by Co. Si louis. Tronto. Princeton; 1984. p. 1261-6.
Kaplan A, Urea Kaplan A. Clin Chem The C. V. Mos by Co. Si louis. Tronto. Princeton; 1984. p. 1257-60.
Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979;95:351-8.
Aebi H. Catalase in vitro. In: Oxygen radicals in biological systems. Methods in enzymology. Vol. 105. Edited by L. Parker. Academic Press: Orlando, Fla; 1984. p. 121-6.
Zhao FJ, Ma JF, Meharg AA, Grath SP. Arsenic uptake and metabolism in plants. New Phytol 2009;181:777–94.
Banchroft JD, Stevens A, Turner DR. Theory and practice of histological techniques 4th ed. Churchill living stone New York: London, San Francisco, Tokyo; 1960. p. 800.
Miller RP, Tadagavadi RK, Ramesh G, Reeves WB. Mechanisms of cisplatin nephrotoxicity. Toxins 2010;2:2490–518.
Abdel Daim MM, El-Ghoneimy A. Synergistic protective effects of ceftriaxone and ascorbic acid against subacute deltamerthrin-induced nephrotoxicity in rats. Ren Fail 2015;37:297–304.
Kawai Y, Satoh T, Hibi D, Ohno Y, Kohda Y, Miura K, et al. The effect of antioxidant on development of fibrosis by cisplatin in rats. J Pharmacol Sci 2009;111:433–43.
Dwivedi VK, Bhatanagar A, Chaudhary M. Protective role of ceftriaxone plus sulbactam with VRP1034 on oxidative stress, hematological and enzymatic parameters in cadmium toxicity induced rat model. Interdiscip Toxicol 2012;5:192–200.
Mousa AA, El-Gansh HAI, Eldaim MAA, Mohamed MAE, Morsi AH, El Sabagh HS. Protective effect of moringa oleifera leaves ethanolic extract against thioacetamide-induced hepatotoxicity in rats via modulation of cellular antioxidant, apoptotic and inflammatory markers. Environ Sci Pollut Res Int 2019;26:32488–504.
Crona DJ, Faso A, Nishijima TF, McGraw KA, Galsky MD, Milowsky MI. A systemic review of strategies to prevent cisplatin-induced nephrotoxicity. Oncologist 2017;22:609–19.
Rehab AS, Magdy MM, Mahmoud BA, Marwa MS. Assessment effect of aloe vera, azadirachta indica and moringa oleifera aqueous extracts on carbon tetrachloride-induced hepatotoxicity in rats. Int J Pharm Pharm Sci 2016;8:83-9.
Mallya R, Chatterjee PK, Vinodini NA, Chatterjee P, Mithra P. Moringa oleifera leaf extract: beneficial effects on cadmium induced toxicities-a review. J Clin Diagn Res 2017;11:CE01–CE04.
Ademiluyi AO, Aladeselu OH, Oboh G, Boligon A A. Drying alters the phenolic constituents, antioxidant properties, α‐amylase and α‐glucosidase inhibitory properties of Moringa (Moringa oleifera) leaf. Food Sci Nutr 2018;6:2123–33.
Oyeleye SI, Adebayo AA, Ogunsuyia OB, Dada FA, Oboh G. Phenolic profile and enzyme inhibitory activities of almond (Terminalia catappa) leaf and stem bark. Int J Food Prop 2017;20:S2810–S282.
Gandhi S, Abranov AY. Mechanism of oxidative stress in neurodegeneration. Oxid Med Cell Longev 2012;3:65–8.
Oboh G. Effect of blanching on the antioxidant property of some tropical green leafy vegetables. J Med Food 2005;38:513–7.
Ramesh G, Reeves WB. TNF-α mediates chemokine and cytokine expression and renal injury in cisplatin nephrotoxicity. J Clin Invest 2002;110:835–42.
Coppin JP, Xu Y, Chen H, Pan MH, Ho CT, Juliani R, et al. Determination of flavonoids by LC/MS and anti-inflammatory activity in Moringa oleifera. J Funct Foods 2013;5:1892–9.
Arjumand W, Seth A, Sultana S. Rutin attenuates cisplatin induced renal inflammation and apoptosis by reducing NKkB, TNF-a and caspase-3 expression in wistar rats. Food Chem Toxicol 2011;49:2013–21.
Hamza AA. Ameliorative effects of Moringa oleifera lam seed extract on liver fibrosis in rats. Food Chem Toxicol 2010;48:345–55.
Tadagavadi RK, Reeves WB. Endogenous IL-10 attenuates cisplatin nephrotoxicity: role of dendritic cells. J Immunol 2010;185:4904–11.
Deng J, Kohda Y, Chiao H. Interleukin-10 inhibits ischemic and cisplatin-induced acute renal injury. Kidney Int 2001;60:2118–28.
Kim MG, Yang HN, Kim HW. IL-10 mediates rosiglitazone-induced kidney protection in cisplatin nephrotoxicity. J Korean Med Sci 2010;25:557–63.
Abarikwu SO, Benjamin S, Ebah SG, Obilor G, Agbam G. Oral administration of Moringa oleifera oil but not coconut oil prevents mercury-induced testicular toxicity in rats. Andrologia 2017;49:e12597.
Famurewa AC, Aja PM, Nwankwo OE, Awoke JN, Maduagwuna EK, Aloke C. Moringa oleifera seed oil or virgin coconut oil supplementation abrogates cerebral neurotoxicity induced by antineoplastic agent methotrexate by suppression of oxidative stress and neuro-inflammation in rats. J Food Biochem 2019;43:e12748.
Zeng K Moringa oleifera seed extract protects against brain damage in both the acute and delayed stages of ischemic stroke. Exp Gerontol 2019;122:99–108.
Sreelatha S, Padma PR. Antioxidant activity and total phenolic content of Moringa oleifera leaves in two stages of maturity. Plant Food Hum Nutr 2009;64:303-11.
Abd-El Reheem AE, Rana AA, Eman MR. Physiological studies of the effect of Moringa olifera and vitamin (C) on hepatotoxicity and oxidative stress induced by lead acetate in male albino rats egypt. Acad J Biol Sci 2019;11:93-104.