Research Article


DOI :10.26650/EurJBiol.2023.1306497   IUP :10.26650/EurJBiol.2023.1306497    Full Text (PDF)

Potential Therapeutic Effect of Lipoic Acid on Methotrexate-Induced Oxidative Stress in Rat Heart

Sehkar OktayŞükriye Çalışkan

Objective: Methotrexate (MTX), an antifolate and antimetabolite, is used in the treatment of cancer and autoimmune diseases, however, it can cause many adverse events. Lipoic acid (LA) has anticancer and antioxidant activities, and due to these properties, it is effective in curing the complications of various disorders. The study aims to investigate the potential therapeutic effect of LA on MTX-induced oxidative stress in the heart tissues of rats.

Materials and Methods: Eighteen Wistar Albino rats were divided equally into 3 groups as follows: Controls, MT group (MTX was injected with a single dose of 20 mg/kg, i.p.) and MT+LA group (MTX was injected with a single dose of 20 mg/kg, i.p. on the first day and LA (dissolved in saline, 50 mg/kg/day, i.p,) was injected for 5 days). On the sixth day, rats were sacrificed under general anesthesia. Total protein, lipid peroxidation (LPO), nitric oxide (NO), sialic acid (SA), and glutathione (GSH) levels, and also catalase (CAT), superoxide dismutase (SOD) and glutathione-s-transferase (GST) activities were determined in 10% (w/v) heart homogenates.

Results: MTX administration significantly increased LPO and NO levels, and SOD activity and significantly decreased GSH level and CAT activity. LA reversed these parameters by decreasing LPO and NO levels and SOD activity, and increasing GSH levels significantly.

Conclusion: LA has beneficial effects on the impaired oxidant/antioxidant status and is effective in reducing oxidative stress during MTX administration in the heart tissue of rats. 


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References

  • 1. Friedman B, Cronstein B. Methotrexate mechanism in treatment of rheumatoid arthritis. Jt Bone Spine. 2019;86(3):301-307. google scholar
  • 2. Sentürk N. Metotreksat. Turkderm. 2016;50(1):18-21. google scholar
  • 3. Ahmed ZSO, Hussein S, Ghandour RA, Azouz AA., El-Sakhawy MA. Evaluation of the effect of methotrexate on the hippocampus, cerebellum, liver, and kidneys of adult male albino rat: Histopathological, immunohistochemical and bio-chemical studies. Acta Histochem. 2021; 123(2):151682. doi: 10.1016/j.acthis.2021.151682 google scholar
  • 4. Yuksel Y, Yuksel R, Yagmurca M, et al. Effects of quercetin on methotrexate-induced nephrotoxicity in rats. Hum Exp Toxicol. 2017;36(1):51-61. google scholar
  • 5. Pisoschi AM, Pop A, Iordache F, Stanca L, Predoi G, Serban AI. Oxidative stress mitigation by antioxidants-an overview on their chemistry and influences on health status. Eur J Med Chem. 2021;209:112891. doi: 10.1016/j.ejmech.2020.112891 google scholar
  • 6. Puig L. Methotrexate: New therapeutic approaches. Actas Dermosifiliogr. 2014;105(6):583-589. google scholar
  • 7. Zwolak I. Protective effects of dietary antioxidants against vanadium-induced toxicity: A review. Oxid Med Cell Longev. 2020;1-14. doi:10.1155/2020/1490316 google scholar
  • 8. Billgren ES, Cicchillo RM, Nesbitt NM, Booker SJ. Lipoic acid biosynthesis and enzymology. Chem Biol. 2010;7:181-212. google scholar
  • 9. Fayez AM, Zakaria S, Moustafa D. Alpha lipoic acid exerts an-tioxidant effect via Nrf2/HO-1 pathway activation and suppresses hepatic stellate cells activation induced by methotrexate in rats. Biomed Pharmacother. 2018;105:428-433. google scholar
  • 10. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951;193:265-275. google scholar
  • 11. Yagi K. Assay for blood plasma or serum. Methods Enzymol. 1984;105:328-337. google scholar
  • 12. Miranda K, 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
  • 13. Warren L. The thiobarbituric acid assay of sialic acids. J Biol Chem. 1959;234:1971-1975. google scholar
  • 14. Beutler E. Gluthatione: Red cell metabolism. A manual biochemical methods. New York: Grune and Stratton; 1975. google scholar
  • 15. Aebi H. Catalase in vitro. In: Methods of enzymatic analysis Bergmeye HU, editor. Wenheim: Verlag Chemie; 1974. google scholar
  • 16. Mylorie AA, Collins H, Umbles C, Kyle J. Erythrocyte SOD activity and other parameters of copper status in rats ingesting lead acetate. Toxicol Appl Pharmacol. 1986; 82:512-520. google scholar
  • 17. Habig WH, Jacoby WB. Assays for differentation of glutathione-s-transferases. Methods Enzymol. 1981; 77:398-405. google scholar
  • 18. Saibeni S, Bollani S, Losco A, et al. The use of methotrexate for treatment of inflammatory bowel disease in clinical practice. Dig Liver Dis. 2012;44(2):123-127. google scholar
  • 19. Deo M, Yung A, Hill S, Rademaker M. Methotrexate for treatment of atopic dermatitis in children and adolescents. Int J Dermatol. 2014;53(8):1037-1041. google scholar
  • 20. 20. Shen S, Yap LM, Prince HM, McCormack CJ. The use of methotrexate in dermatology: A review. Aust J Dermatol. 2012;53(1):1-18. google scholar
  • 21. Mahmoud AM, Hozayen WG, Ramadan SM. Berberine amelio-rates methotrexate-induced liver injury by activating Nrf2/HO-1 pathway and PPARy, and suppressing oxidative stress and apop-tosis in rats. Biomed Pharmacother. 2017; 94: 280-291. google scholar
  • 22. Malayeri A, Badparva R, Mombeini MA, Khorsandi L, Goudarzi M. Naringenin: A potential natural remedy against methotrexate-induced hepatotoxicity in rats. Drug Chem Toxicol. 2020;28:1-8. google scholar
  • 23. Mehrzadi S, Safa M, Kamrava SK, Darabi R, Hayat P, Mote-valian M. Protective mechanisms of melatonin against hydrogen-peroxide-induced toxicity in human bone-marrow-derived mes-enchymal stem cells. Can J Physiol Pharmacol. 2017;95:773-786. google scholar
  • 24. Uzar E, Koyuncuoglu HR, Uz E, et al. The activities of antiox-idant enzymes and the level of malondialdehyde in cerebellum of rats subjected to methotrexate: protective effect of caffeic acid phenethyl ester. Mol Cell Biochem. 2006;291:63-68. google scholar
  • 25. Kalantar M, Kalantari H, Goudarzi M, et al. Crocin ameliorates methotrexate-induced liver injury via inhibition of oxidative stress and inflammation in rats. Pharmacol Rep. 2019;71(4):746-752. google scholar
  • 26. Khatab LA, Abdel-Raheem IT, Ghoneim AI. Protective effects of melatonin and L-carnitine against methotrexate-induced tox-icity in isolated rat hepatocytes. Naunyn-Schmiedebergs Arch Pharmacol. 2022;395:87-97. google scholar
  • 27. Owumi SE, AjijolaIJ, Agbeti OM. Hepatorenal protective effects of protocatechuic acid in rats administered with anticancer drug methotrexate. Hum Exp Toxicol. 2019;38(11):1254-1265. google scholar
  • 28. Rajappa M, Shanmugam R, Munisamy M, et al. Effect of antip-soriatic therapy on oxidative stress index and sialic acid levels in patients with psoriasis. Int J Dermatol. 2016;55(8):422-430. google scholar
  • 29. Vardi N, Parlakpinar H, Cetin A, Erdogan A, Cetin Ozturk I. Protective effect of fi carotene on methotrexate-induced oxidative liver damage. Toxicol Pathol. 2010;38:592-597. google scholar
  • 30. El-Sheikh AA, Morsy MA, Abdalla AM, Hamouda AH, Al-haider IA. Mechanisms of thymoquinone hepatorenal protec-tion in methotrexate-induced toxicity in rats. Mediators Inflamm. 2015; 859383. doi:10.1155/2015/859383 google scholar
  • 31. Deluao JC, Winstanley Y, Robker RL, Pacella-Ince L, Gonzalez MB, McPherson NO. oxidative stress and reproductive function: Reactive oxygen species in the mammalian pre-implantation em-bryo. Reprod. 2022;164(6):95-108. google scholar
  • 32. Quiros Y, Blanco-Gozalo V, Sanchez-Gallego JI, et al. Cardiotrophin-1 therapy prevents gentamicin-induced nephrotox-icity in rats. Pharmacol Res. 2016;107:137-146. google scholar
  • 33. Dhanesha M, Singh K, Bhori M, Marar T. Impact of antiox-idant supplementation on toxicity of methotrexate: an in vitro study on erythrocytes using vitamin E. Asian J Pharm Clin Res. 2015;8(3):339-343. google scholar
  • 34. Selvakumar E, Prahalathan C, Mythili Y, Varalakshmi P.Beneficial effects of DL-a-lipoic acid on cyclophosphamide-induced oxidative stress in mitochondrial fractions of rat testis. Chem Biol Interact. 2005;152(1):59-66. google scholar
  • 35. Armagan I, Bayram D, Candan IA, et al. Effects of pentoxifylline and alpha lipoic acid on methotrexate-induced damage in liver and kidney of rats. Environ Toxicol Pharmacol. 2015;39(3):1122-1131. google scholar

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APA

Oktay, S., & Çalışkan, Ş. (2023). Potential Therapeutic Effect of Lipoic Acid on Methotrexate-Induced Oxidative Stress in Rat Heart. European Journal of Biology, 82(2), 306-310. https://doi.org/10.26650/EurJBiol.2023.1306497


AMA

Oktay S, Çalışkan Ş. Potential Therapeutic Effect of Lipoic Acid on Methotrexate-Induced Oxidative Stress in Rat Heart. European Journal of Biology. 2023;82(2):306-310. https://doi.org/10.26650/EurJBiol.2023.1306497


ABNT

Oktay, S.; Çalışkan, Ş. Potential Therapeutic Effect of Lipoic Acid on Methotrexate-Induced Oxidative Stress in Rat Heart. European Journal of Biology, [Publisher Location], v. 82, n. 2, p. 306-310, 2023.


Chicago: Author-Date Style

Oktay, Sehkar, and Şükriye Çalışkan. 2023. “Potential Therapeutic Effect of Lipoic Acid on Methotrexate-Induced Oxidative Stress in Rat Heart.” European Journal of Biology 82, no. 2: 306-310. https://doi.org/10.26650/EurJBiol.2023.1306497


Chicago: Humanities Style

Oktay, Sehkar, and Şükriye Çalışkan. Potential Therapeutic Effect of Lipoic Acid on Methotrexate-Induced Oxidative Stress in Rat Heart.” European Journal of Biology 82, no. 2 (Mar. 2024): 306-310. https://doi.org/10.26650/EurJBiol.2023.1306497


Harvard: Australian Style

Oktay, S & Çalışkan, Ş 2023, 'Potential Therapeutic Effect of Lipoic Acid on Methotrexate-Induced Oxidative Stress in Rat Heart', European Journal of Biology, vol. 82, no. 2, pp. 306-310, viewed 3 Mar. 2024, https://doi.org/10.26650/EurJBiol.2023.1306497


Harvard: Author-Date Style

Oktay, S. and Çalışkan, Ş. (2023) ‘Potential Therapeutic Effect of Lipoic Acid on Methotrexate-Induced Oxidative Stress in Rat Heart’, European Journal of Biology, 82(2), pp. 306-310. https://doi.org/10.26650/EurJBiol.2023.1306497 (3 Mar. 2024).


MLA

Oktay, Sehkar, and Şükriye Çalışkan. Potential Therapeutic Effect of Lipoic Acid on Methotrexate-Induced Oxidative Stress in Rat Heart.” European Journal of Biology, vol. 82, no. 2, 2023, pp. 306-310. [Database Container], https://doi.org/10.26650/EurJBiol.2023.1306497


Vancouver

Oktay S, Çalışkan Ş. Potential Therapeutic Effect of Lipoic Acid on Methotrexate-Induced Oxidative Stress in Rat Heart. European Journal of Biology [Internet]. 3 Mar. 2024 [cited 3 Mar. 2024];82(2):306-310. Available from: https://doi.org/10.26650/EurJBiol.2023.1306497 doi: 10.26650/EurJBiol.2023.1306497


ISNAD

Oktay, Sehkar - Çalışkan, Şükriye. Potential Therapeutic Effect of Lipoic Acid on Methotrexate-Induced Oxidative Stress in Rat Heart”. European Journal of Biology 82/2 (Mar. 2024): 306-310. https://doi.org/10.26650/EurJBiol.2023.1306497



TIMELINE


Submitted29.05.2023
Accepted19.08.2023
Published Online27.09.2023

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