Moringa oleifera Ethanolic Extract Prevents Oxidative Damage on Lens Caused by Sodium Valproate Used in Epilepsy Treatment

Year 2023, Volume: 82 Issue: 2, 289 - 295, 21.12.2023

Eda Dağsuyu , Umar Faruk Magaji , Özlem Saçan , Refiye Yanardağ

https://doi.org/10.26650/EurJBiol.2023.1328517

Abstract

Objective: Valproic acid/valproate (VPA) is an antiepileptic agent that is structurally a short-chain fatty acid. It triggers the generation of reactive oxidants that can affect lens tissue. Moringa oleifera Lam. is a prevalent plant that grows in Asia, Africa and South Africa. The plant has anti-inflammatory, hepatoprotective, nephroprotective and cardioprotective activities.

Materials and Methods: The effect of 70% ethanol extract of the Moringa oleifera leaves was examined on VPA-induced lens tissue damage in this study. Experimental rats were grouped into four: the control (C), Moringa extract (M), VPA, and VPA+M group.Mextract and VPA respectively were administered orally at a dose of 0.3 and 0.5 grams per kg body weight daily for fifteen days. The lens tissues of the rats were taken after sacrifice. Oxidative stress markers including glutathione, lipid peroxidation, and advanced oxidation protein products levels, glutathione reductase, glutathione peroxidase, glutathione-S-transferase, and superoxide dismutase activities, total oxidant status, total antioxidant status, reactive oxygen species, nitric oxide levels and aldose reductase and sorbitol dehydrogenase activities were determined.

Results: Tissue homogenates showed a significant decrease in glutathione and total antioxidants, as well as an altered activity of superoxide dismutase and glutathione-related enzymes in VPA groups. Moreover, a significant rise in the concentration of nitric oxide, reactive oxygen species and total oxidants, coupled with higher aldose reductase and sorbitol dehydrogenase activities were detected. In contrast, changes in the levels of these parameters were offset in the VPA+M group by Moringa extract.

Conclusion: This suggests that Moringa oleifera leaves are an excellent nutritional composite for mitigating the damaging properties of VPA.

Keywords

Antioxidant enzymes, Lens, Moringa oleifera, Oxidative damage, Valproic acid.

References

• Ghodke-Puranik Y, Thorn CF, Lamba JK, et al. Valproic acid pathway: Pharmacokinetics and pharmacodynamics. Pharmacogenet Genom. 2013;23:236-241. google scholar
• Santos BL, Fernandes RM, Neves FF. Valproic acid-induced pan-creatitis in an adult. Arq Neuropsiquiatr. 2010;68:135-136. google scholar
• Emekli-Alturfan E, Alev B, Tunali S, et al. Effects of edaravone on cardiac damage in valproic acid induced toxicity. Ann Clin Lab Sci. 2015;45:166-172. google scholar
• Oktay S, Alev B, Tunali S, et al. Edaravone ameliorates the ad-verse effects of valproic acid toxicity in small intestine. Hum Exp Toxicol. 2015;34:654-661. google scholar
• Turkyılmaz IB, Altas N, Arisan I, Yanardag R. Effect of vitamin B6 on brain damage in valproic acid induced toxicity. J Biochem Mol Toxicol. 2021;35:e22855.doi:10.1002/jbt.22847. google scholar
• Celik E, Tunali S, Gezginci-Oktayoglu S, Bolkent S, Can A, Ya-nardag R. Vitamin U prevents valproic acid-induced liver injury through supporting enzymatic antioxidant system and increasing hepatocyte proliferation triggered by inflammation and apoptosis. Toxicol Mech Methods. 2021;31:600-608. google scholar
• Gezginci-Oktayoglu S, Turkyilmaz IB, Ercin M, Yanardag R, Bolkent S. Vitamin U has a protective effect on valproic acid-induced renal damage due to its anti-oxidant, anti-inflammatory, and anti-fibrotic properties. Protoplasma. 2016;253:127-135. google scholar
• Bayrak BB, Yılmaz S, Hacıhasanoglu CN, Yanardag R. The effects of edaravone, a free-radical scavenger in lung in-jury induced by valproic acid demonstrated via different bio-chemical parameters. J Biochem Mol Toxicol. 2021; 35(9): e22847.doi:10.1002/jbt.22847. google scholar
• Tunali S, Kahraman S, Yanardag R. Vitamin U, a novel free radical scavenger, prevents lens injury in rats administered with valproic acid. Hum Exp Toxicol. 2014; 34:904-910. google scholar
• Milla PG, Penalver R, Nieto G. Health benefits of uses and applications of Moringa oleifera in bakery products. Plants. 2021;10:318. doi:10.3390/plants10020318 google scholar
• Sultana B, Anwar F. Flavonols (kaempeferol, quercetin, myricetin) contents of selected fruits, vegetables and medicinal plants. Food Chem. 2008;108:879-884. google scholar
• Magaji UF, Sacan O, Yanardag R. Alpha amylase, alpha glucosi-dase and glycation inhibitory activity of Moringa oleifera extracts. SAfrJBot. 2020;128:225-230. google scholar
• Oldoni TLC, Merlin N, Bicas TC, et al. Antihyperglycemic ac-tivity of crude extract and isolation of phenolic compounds with antioxidant activity from Moringa oleifera Lam. leaves grown in Southern Brazil. Food Res Int. 2021;141:110082. doi:10.1016/j.foodres.2020.110082 google scholar
• Waterman C, Cheng DM, Rojas-Silva P, et al. Stable, water ex-tractable isothiocyanates from Moringa oleifera leaves attenuate inflammation in vitro. Phytochemistry. 2014;103:114-122. google scholar
• Toppo R, Roy BK, Gora RH, Baxla SL, Kumar P. Hepatoprotec-tive activity of Moringa oleifera against cadmium toxicity in rats. Vet World. 2015;8:537-540. google scholar
• Ouedraogo M, Lamien-Sanou A, Ramde N, et al. Protective effect of Moringa oleifera leaves against gentamicin-induced nephrotox-icity in rabbits. Exp Toxicol Pathol. 2013;65:335-339. google scholar
• Saini RK, Sivanesan I, Keum YS. Phytochemicals of Moringa oleifera: A review of their nutritional, therapeutic and indus-trial significance. 3 Biotech. 2016;6:203. doi:10.1007/s13205-016-0526-3 google scholar
• Ali A, Garg P, Goyal R, et al. A novel herbal hydrogel formula-tion of Moringa oleifera for wound healing. Plants. 2021;10:25. doi:10.3390/plants10010025 google scholar
• Ertik O, Magaji U.F, Sacan O, Yanardag R. Effect of Moringa oleifera leaf extract on valproate-induced ox-idative damage in muscle. Drug Chem Toxicol. 2022. doi:10.1080/01480545.2022.2144876. google scholar
• Beutler E. Reduced Glutathione (GSH): Red blood cell metabolism: A manual of biochemical methods, In: Bergmeyen,HV ed. New York, Grune & Stratton, 1975, 112-114. google scholar
• Ledwozyw A, Michalak J, Stepien A, Kadziolka A. The relation-ship between plasma triglycerides, cholesterol, total lipids and lipid peroxidation products during human atheroschlerosis. Clin Chim Acta. 1986;155:275-283. google scholar
• Barretto OC, Beutler E. The sorbitol-oxidizing enzyme of red blood cells. J Lab Clin Med. 1975;85:645-649. google scholar
• Hayman S, Kinoshita JH. Isolation and properties of lens aldose reductase. J Biol Chem. 1965;240:877-882. google scholar
• Beutler E. Red cell metabolism: A manuel of biochemical meth-ods, London, Grune & Stratton, 1971;68-70. google scholar
• Mylroie AA, Collins AH, Umbles C, Kyle J. Erythrocyte super-oxide dismutase activity and other parameters of copper status in rats ingesting lead acetate. Toxicol Appl Pharmacol. 1986;82:512-520. google scholar
• Wendel A. Glutathione peroxidase. Methods Enzymol. 1981;77:325-333. google scholar
• Habig WH, Jakoby WB. Assays for differentiation of glutathione S-transferases. Methods Enzymol. 1981;77:398-405. google scholar
• Erel O. A new automated colorimetric method for measuring total oxidant status. Clin Biochem. 2005;38:1103-1111. google scholar
• Erel O. A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clin Biochem. 2004;37: 277-285. google scholar
• Zhang Y, Chen J, Ji H, Xiao ZG, Shen P, Xu LH. Protec-tive effects of Danshen injection against erectile dysfunction via suppression of endoplasmic reticulum stress activation in a streptozotocin-induced diabetic rat model. BMC Compl Altern Med. 2018;18:343. doi:10.1186/s12906-018-2414-3 google scholar
• Miranda KM, Espey MG, Wink DA. A rapid, simple spectropho-tometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide. 2001;5:62-71. google scholar
• Witko-Sarsat V, Friedlander M, Capeillere-Blandin C, et al. Ad-vanced oxidation protein products as a novel marker of oxidative stress in uremia. Kidney Int. 1996;49: 1304-1313. google scholar
• Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the folin phenol reagent. J Biol Chem. 1951;193:265-275. google scholar
• Aktas Z, Cansu A, Erdoğan D, et al. Retinal ganglion cell toxicity due to oxcarbazepine and valproic acid treatment in rat. Seizure. 2009;18:396-399. google scholar
• Coppola S, Ghibelli L. GSH extrusion and the mitochondrial path-way of apoptotic signalling. Biochem Soc Trans. 2000;28:56-61. google scholar
• Tong V, Teng XW, Chang TKH, Abbott FS. Valproic acid I: Time course of lipid peroxidation biomarkers, liver toxicity, and val-proic acid metabolite levels in rats. Toxicol Sci. 2005;86:427-435. google scholar
• Muthukumar K, Rajakumar S, Sarkar MN, Nachiappan V. Glu-tathione peroxidase3 of Saccharomyces cerevisiae protects phos-pholipids during cadmium-induced oxidative stress. Antonie van Leeuwenhoek. 2011;9:761-771. google scholar
• Oakley A. Glutathione transferases: A structural perspective. Drug Metab Rev. 2011; 43:138-151. google scholar
• Stawiarska-Pieta B, Paszczela A, Grucka-Mamczar E, Szaflarska-Stojko E, Birkner E. The effect of antioxidative vitamins A and E and coenzyme Q on the morphological picture of the lungs and pancreata of rats intoxicated with sodium fluoride. Food Chem Toxicol. 2009;47:2544-2550. google scholar
• Wu ZM, Yin XX, Ji L, et al. Ginkgo biloba extract prevents against apoptosis induced by high glucose in human lens epithelial cells. Acta Pharmacol Sin. 2008;29:1042-1050. google scholar
• El-Kabbani O, Darmanin C, Chung RP. Sorbitol dehydroge-nase: Structure, function and ligand design. Curr Med Chem. 2004;11:465-476. google scholar