Journal of Basic Research in Medical Sciences
J Basic Res Med Sci
Volume 13, Issue 4 (9-2026)
jbrms 2026, 13(4): 49-57 |
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Mohammadi R, Vatannejad A, Kheirollahi A. Impact of Folate Supplementation on Liver Oxidative Stress Indicators in Diabetic Rats Induced by Streptozotocin. jbrms 2026; 13 (4) :49-57
URL: http://jbrms.medilam.ac.ir/article-1-1077-en.html
URL: http://jbrms.medilam.ac.ir/article-1-1077-en.html
Department of Comparative Biosciences, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran , vatannejad@ut.ac.ir
Abstract: (18 Views)
Introduction: Diabetes can cause metabolic disorders and the liver is an organ at risk due to its crucial role in glucose and lipid metabolism. Oxidative stress and inflammation play key roles in the development of diabetic liver disease. Folate, an antioxidant water-soluble B-vitamin, might prove beneficial in the treatment of these conditions through decreasing oxidative stress and regulating the metabolism of homocysteine. The present study was designed to investigate the effect of folate supplementation on glucose metabolism, redox status and liver dysfunction in streptozotocin-induced diabetic rats.
Materials & Methods: Adult male Wistar rats (200 +/- 20 g) were randomly divided into three groups (n=6): control, STZ-induced diabetic and folate-treated diabetic. Diabetic status in the two diabetic groups was induced by a single intraperitoneal (i.p.) injection of streptozotocin (55 mg/kg). Folate (15 mg/kg, i.p.) was administered once daily for 4 weeks in the therapy group. At end of the study, fasting blood sugar (FBS), serum liver enzymes, hepatic MDA, SOD activity and TAC were determined. Data were analyzed by one-way ANOVA and Dunnett’s post hoc test.
Results: Folate supplementation resulted in mild improvement in body weight, FBS, ALT and AST levels in diabetic rats. However, these changes were not significant when compared to untreated diabetic animals. There were no significant changes in the hepatic levels of MDA and TAC, and a mild non-significant increase in SOD activity after the administration of folate.
Conclusion: Folate exerted small, possibly beneficial effects on metabolic and hepatic oxidative stress in STZ-induced diabetic rats. The slight improvement in antioxidant status, although not statistically significant, suggests that folate may have protective effects in diabetic conditions. Its therapeutic efficacy may be enhanced when used as an adjunct to conventional antidiabetic treatments.
Materials & Methods: Adult male Wistar rats (200 +/- 20 g) were randomly divided into three groups (n=6): control, STZ-induced diabetic and folate-treated diabetic. Diabetic status in the two diabetic groups was induced by a single intraperitoneal (i.p.) injection of streptozotocin (55 mg/kg). Folate (15 mg/kg, i.p.) was administered once daily for 4 weeks in the therapy group. At end of the study, fasting blood sugar (FBS), serum liver enzymes, hepatic MDA, SOD activity and TAC were determined. Data were analyzed by one-way ANOVA and Dunnett’s post hoc test.
Results: Folate supplementation resulted in mild improvement in body weight, FBS, ALT and AST levels in diabetic rats. However, these changes were not significant when compared to untreated diabetic animals. There were no significant changes in the hepatic levels of MDA and TAC, and a mild non-significant increase in SOD activity after the administration of folate.
Conclusion: Folate exerted small, possibly beneficial effects on metabolic and hepatic oxidative stress in STZ-induced diabetic rats. The slight improvement in antioxidant status, although not statistically significant, suggests that folate may have protective effects in diabetic conditions. Its therapeutic efficacy may be enhanced when used as an adjunct to conventional antidiabetic treatments.
Keywords: Diabetes, Oxidative Stress, Liver Function, Folate, Malondialdehyde, Total Antioxidant Capacity, Streptozotocin
Type of Study: Research |
Subject:
Clinical Biochemistry
Received: 2026/05/9 | Accepted: 2026/06/23 | Published: 2026/09/28
Received: 2026/05/9 | Accepted: 2026/06/23 | Published: 2026/09/28
References
1. Petersen, M.C., D.F. Vatner, and G.I. Shulman, Regulation of hepatic glucose metabolism in health and disease. Nature reviews endocrinology, 2017. 13(10): p. 572-587, [DOI:10.1038/nrendo.2017.80.]
2. Federation, I.D. Diabetes facts & figures. 2025 7 Jun 2025]; Available from: https://idf.org/about-diabetes/diabetes-facts-figures/.
3. Gabbia, D., L. Cannella, and S. De Martin, The role of oxidative stress in NAFLD–NASH–HCC transition—focus on NADPH oxidases. Biomedicines, 2021. 9(6): p. 687, [DOI:10.3390/biomedicines9060687.]
4. Chen, X., et al., Oxidative stress in diabetes mellitus and its complications: From pathophysiology to therapeutic strategies. Chinese Medical Journal, 2025. 138(1): p. 15-27, [DOI:10.1097/CM9.0000000000003230.]
5. De Deus, I.J., et al., Role of NLRP3 inflammasome and oxidative stress in hepatic insulin resistance and the ameliorative effect of phytochemical intervention. Frontiers in pharmacology, 2023. 14: p. 1188829, [DOI:10.3389/fphar.2023.1188829.]
6. Ebaid, H., et al., Folic acid and melatonin mitigate diabetic nephropathy in rats via inhibition of oxidative stress. Nutrition & metabolism, 2020. 17: p. 1-14, [DOI:10.1186/s12986-019-0419-7.]
7. Cui, S., et al., Folic acid modulates VPO1 DNA methylation levels and alleviates oxidative stress-induced apoptosis in vivo and in vitro. Redox biology, 2018. 19: p. 81-91, [DOI:10.1016/j.redox.2018.08.005.]
8. Zal, F., et al., Combination of vitamin E and folic acid ameliorate oxidative stress and apoptosis in diabetic rat uterus. Int J Vitam Nutr Res, 2014. 84(1-2): p. 55-64, [DOI:10.1024/0300-9831/a000193.]
9. Bokayeva, K., et al. The effect of folic acid supplementation on endothelial function and arterial stiffness markers in adults: a systematic review and meta-analysis. in Healthcare. 2023, [DOI:10.3390/healthcare11182524.]
10. Zamani, M., et al., The effects of folic acid supplementation on endothelial function in adults: a systematic review and dose-response meta-analysis of randomized controlled trials. Nutrition journal, 2023. 22(1): p. 12, [DOI:10.1186/s12937-023-00843-y.]
11. Esse, R., et al., The contribution of homocysteine metabolism disruption to endothelial dysfunction: state-of-the-art. International journal of molecular sciences, 2019. 20(4): p. 867, [DOI:10.3390/ijms20040867.]
12. Yuan, D., et al., Mechanism of homocysteine-mediated endothelial injury and its consequences for atherosclerosis. Frontiers in cardiovascular medicine, 2023. 9: p. 1109445, [DOI:10.3389/fcvm.2022.1109445.]
13. RahimBakhsh, A., et al., Protective effects of S-adenosyl methionine on oxidative stress and tissue damage in STZ-induced diabetic rats. Amino acids, 2025. 57(1): p. 1-12, [DOI:10.1007/s00726-025-03471-4.]
14. Mohammadi R, Vatannejad A, Kheirollahi A, Shokrpoor S, RahimBakhsh A, Sedighi Pashaki T. Effects of Folate supplementation on the kidney in Streptozotocin-Induced Diabetic Rats. jbrms 2026; 13 (3) :19-29. http://jbrms.medilam.ac.ir/article-1-1062-en.html.
15. Furman, B.L., Streptozotocin‐induced diabetic models in mice and rats. Current protocols, 2021. 1(4): p. e78, [DOI:10.1002/cpz1.78.]
16. Mutavdzin, S., et al., The effects of folic acid administration on cardiac oxidative stress and cardiovascular biomarkers in diabetic rats. Oxidative medicine and cellular longevity, 2019. 2019(1): p. 1342549, [DOI:10.1155/2019/1342549.]
17. Shooshtari, M.K., A.A. Moazedi, and G.A. Parham, Memory and motor coordination improvement by folic Acid supplementation in healthy adult male rats. Iranian Journal of Basic Medical Sciences, 2012. 15(6): p. 1173, [DOI:10.22038/ijbms.2012.4937.]
18. Mutavdzin, S., et al., The effect of folic acid administration on cardiac tissue matrix metalloproteinase activity and hepatorenal biomarkers in diabetic rats. Canadian Journal of Physiology and Pharmacology, 2019. 97(9): p. 893-901, [DOI:10.1139/cjpp-2019-0027.]
19. Asbaghi, O., et al., Effects of folic acid supplementation on oxidative stress markers: a systematic review and meta-analysis of randomized controlled trials. Antioxidants, 2021. 10(6): p. 871, [DOI:10.3390/antiox10060871.]
20. Kaur, G., et al., Garlic and resveratrol attenuate diabetic complications, loss of β-cells, pancreatic and hepatic oxidative stress in streptozotocin-induced diabetic rats. Frontiers in pharmacology, 2016. 7: p. 360, [DOI:10.3389/fphar.2016.00360.]
21. Huma, K., et al., A comparative analysis of superoxide dismutase 1 level in diabetics with and without neuropathy. J Coll Physicians Surg Pak, 2021. 31(07): p. 765-769, [DOI:10.29271/jcpsp.2021.07.765.]
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