Abstract
Oxidative stress is critical in the occurrence and development of diabetes and its related complications. l-serine has recently been shown to reduce oxidative stress, the incidence of autoimmune diabetes and improve glucose homeostasis. The aim of this study was to investigate the effects of daily l-serine administration on blood glucose, renal function and oxidative stress markers in the kidney of streptozotocin-induced diabetic mice. Eighteen C57BL/6 male mice were randomly divided into three groups (n = 6 per group). Streptozotocin was used to induce diabetes and a group of diabetic mice was treated with 280 mg/day of l-serine dissolved in drinking water for 4 weeks. The level of blood glucose, biochemical markers of renal function (total protein, urea, creatinine and albumin) and oxidative stress markers (protein carbonyls, malondialdehyde, glutathione peroxidase, superoxide dismutase and catalase) were measured using spectrophotometry. The results indicated that l-serine significantly decreased the glucose level in diabetic mice (188.6 ± 22.69 mg/dL, P = 0.02). Moreover, treatment of diabetic mice with l-serine reduced protein carbonyls (3.249 ± 0.9165 nmol/mg protein, P < 0.05) and malondialdehyde levels (1.891 ± 0.7696 μM/mg protein, P = 0.051). However, l-serine showed no significant effects on renal function, and a slight reduction in histopathological changes was observed in mice receiving l-serine. This study revealed that l-serine effectively ameliorates oxidative stress in kidney tissue and reduces the blood glucose concentration in diabetic mice.
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References
Asmat U, Abad K, Ismail K (2016) Diabetes mellitus and oxidative stress—a concise review. Saudi Pharm J 24(5):547–553
Bartsch H, Nair J (2004) Oxidative stress and lipid peroxidation-derived DNA-lesions in inflammation driven carcinogenesis. Cancer Detect Prev 28(6):385–391
Bertea M, Rütti MF, Othman A, Marti-Jaun J, Hersberger M, von Eckardstein A, Hornemann T (2010) Deoxysphingoid bases as plasma markers in diabetes mellitus. Lipids Health Dis 9(1):1–7
Bervoets L, Massa G, Guedens W, Louis E, Noben J-P, Adriaensens P (2017) Metabolic profiling of type 1 diabetes mellitus in children and adolescents: a case–control study. Diabetol Metab Syndr 9(1):1–8
Bokov A, Chaudhuri A, Richardson A (2004) The role of oxidative damage and stress in aging. Mech Ageing Dev 125(10–11):811–826
Calcutt NA, Cooper ME, Kern TS, Schmidt AM (2009) Therapies for hyperglycaemia-induced diabetic complications: from animal models to clinical trials. Nat Rev Drug Discov 8(5):417–430
Cruz M, Maldonado-Bernal C, Mondragon-Gonzalez R, Sanchez-Barrera R, Wacher N, Carvajal-Sandoval G, Kumate J (2008) Glycine treatment decreases proinflammatory cytokines and increases interferon-γ in patients with Type 2 diabetes. J Endocrinol Invest 31:694–699
Cummings NE, Williams EM, Kasza I, Konon EN, Schaid MD, Schmidt BA, Poudel C, Sherman DS, Yu D, Arriola Apelo SI (2018) Restoration of metabolic health by decreased consumption of branched-chain amino acids. J Physiol 596(4):623–645
Dalle-Donne I, Rossi R, Giustarini D, Milzani A, Colombo R (2003) Protein carbonyl groups as biomarkers of oxidative stress. Clin Chim Acta 329(1–2):23–38
Dandare SU, Ezeonwumelu IJ, Shinkafi TS, Magaji UF, Adio AAI, Ahmad K (2021) L-alanine supplementation improves blood glucose level and biochemical indices in alloxan-induced diabetic rats. J Food Biochem 45(1):e13590
de Koning TJ, Snell K, Duran M, Berger R, Poll-The B-T, Surtees R (2003) l-Serine in disease and development. Biochem J 371(3):653–661. https://doi.org/10.1042/bj20021785
Drábková P, Šanderová J, Kovařík J, KanĎár R (2015) An assay of selected serum amino acids in patients with type 2 diabetes mellitus. Adv Clin Exp Med 24(3):447–451
Gaweł S, Wardas M, Niedworok E, Wardas P (2004) Malondialdehyde (MDA) as a lipid peroxidation marker. Wiadomosci Lekarskie (warsaw, Poland 1960) 57(9–10):453–455
Gonzalez-Ortiz M, Medina-Santillan R, Martinez-Abundis E, von Drateln CR (2001) Effect of glycine on insulin secretion and action in healthy first-degree relatives of type 2 diabetes mellitus patients. Horm Metab Res 33(06):358–360
Gui T, Li Y, Zhang S, Alecu I, Chen Q, Zhao Y, Hornemann T, Kullak-Ublick GA, Gai Z (2021) Oxidative stress increases 1-deoxysphingolipid levels in chronic kidney disease. Free Radical Biol Med 164:139–148
Holm LJ, Buschard K (2019) L-serine: a neglected amino acid with a potential therapeutic role in diabetes. APMIS 127(10):655–659
Holm LJ, Haupt-Jorgensen M, Larsen J, Giacobini JD, Bilgin M, Buschard K (2018) l-serine supplementation lowers diabetes incidence and improves blood glucose homeostasis in NOD mice. PLoS ONE 13(3):e0194414
Hu S, Han M, Rezaei A, Li D, Wu G, Ma X (2017) l-arginine modulates glucose and lipid metabolism in obesity and diabetes. Curr Protein Pept Sci 18(6):599–608
Karusheva Y, Koessler T, Strassburger K, Markgraf D, Mastrototaro L, Jelenik T, Simon M-C, Pesta D, Zaharia O-P, Bódis K (2019) Short-term dietary reduction of branched-chain amino acids reduces meal-induced insulin secretion and modifies microbiome composition in type 2 diabetes: a randomized controlled crossover trial. Am J Clin Nutr 110(5):1098–1107
Kim KY, Hwang S-K, Park SY, Kim MJ, Kim YH (2019) l-Serine protects mouse hippocampal neuronal HT22 cells against oxidative stress-mediated mitochondrial damage and apoptotic cell death. Free Radical Biol Med 141:447–460
Mamenko M, Lysikova DV, Spires DR, Tarima SS, Ilatovskaya DV (2022) Practical notes on popular statistical tests in renal physiology. Am J Physiol-Renal Physiol 323(4):F389–F400
Mansour A, Mohajeri-Tehrani MR, Qorbani M, Heshmat R, Larijani B, Hosseini S (2015) Effect of glutamine supplementation on cardiovascular risk factors in patients with type 2 diabetes. Nutrition 31(1):119–126
Maralani MN, Movahedian A, Javanmard SH (2012) Antioxidant and cytoprotective effects of l-Serine on human endothelial cells. Res Pharma Sci 7(4):209
Maritim A, Sanders A, Watkins-Iii J (2003) Diabetes, oxidative stress, and antioxidants: a review. J Biochem Mol Toxicol 17(1):24–38
Muoio DM, Newgard CB (2008) Molecular and metabolic mechanisms of insulin resistance and β-cell failure in type 2 diabetes. Nat Rev Mol Cell Biol 9(3):193–205
Mwinyi J, Boström A, Fehrer I, Othman A, Waeber G, Marti-Soler H, Vollenweider P, Marques-Vidal P, Schiöth HB, Von Eckardstein A (2017) Plasma 1-deoxysphingolipids are early predictors of incident type 2 diabetes mellitus. PLoS ONE 12(5):e0175776
Papatheodorou K, Banach M, Bekiari E, Rizzo M, Edmonds M (2018) Complications of diabetes 2017. vol 2018. Hindawi
Prattichizzo F, De Nigris V, Mancuso E, Spiga R, Giuliani A, Matacchione G, Lazzarini R, Marcheselli F, Recchioni R, Testa R (2018) Short-term sustained hyperglycaemia fosters an archetypal senescence-associated secretory phenotype in endothelial cells and macrophages. Redox Biol 15:170–181
Rains JL, Jain SK (2011) Oxidative stress, insulin signaling, and diabetes. Free Radical Biol Med 50(5):567–575
Rinschen MM, Palygin O, El-Meanawy A, Domingo-Almenara X, Palermo A, Dissanayake LV, Golosova D, Schafroth MA, Guijas C, Demir F (2022) Accelerated lysine metabolism conveys kidney protection in salt-sensitive hypertension. Nat Commun 13(1):4099
Rösen P, Nawroth P, King G, Möller W, Tritschler HJ, Packer L (2001) The role of oxidative stress in the onset and progression of diabetes and its complications: asummary of a Congress Series sponsored byUNESCO-MCBN, the American Diabetes Association and the German Diabetes Society. Diabetes Metab Res Rev 17(3):189–212
Speakman JR, Selman C (2011) The free-radical damage theory: accumulating evidence against a simple link of oxidative stress to ageing and lifespan. BioEssays 33(4):255–259
Vangipurapu J, Stancáková A, Smith U, Kuusisto J, Laakso M (2019) Nine amino acids are associated with decreased insulin secretion and elevated glucose levels in a 7.4-year follow-up study of 5181 Finnish men. Diabetes 68(6):1353–1358
Wu D, Cederbaum AI (2003) Alcohol, oxidative stress, and free radical damage. Alcohol Res Health 27(4):277
Wu KK, Huan Y (2008) Streptozotocin-induced diabetic models in mice and rats. Curr Protoc Pharmacol. https://doi.org/10.1002/0471141755.ph0547s40. (Chapter 5:Unit 5.47)
Würtz P, Soininen P, Kangas AJ, Rönnemaa T, Lehtimäki T, Kähönen M, Viikari JS, Raitakari OT, Ala-Korpela M (2013) Branched-chain and aromatic amino acids are predictors of insulin resistance in young adults. Diabetes Care 36(3):648–655
Zhou X, Zhang H, He L, Wu X, Yin Y (2018) Long-term L-serine administration reduces food intake and improves oxidative stress and Sirt1/NFκB signaling in the hypothalamus of aging mice. Front Endocrinol 9:476
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We thank the University of Tehran for the support of this manuscript.
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This study was supported by the University of Tehran.
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AK and AV contributed to the study concept and design. Material preparation and data collection were performed by FEL and MSN. SA contributed to the methodology. SS performed the histopathological analysis. The first draft of the manuscript was written by FEL. All authors reviewed and edited the manuscript and approved the final version of the manuscript.
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All of the experimental procedures were approved the Animal Ethics Committee from the University of Tehran (Approved No.: IR.UT.VETMED.REC.1401.012).
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Langroudi, F.E., Narani, M.S., Kheirollahi, A. et al. Effect of l-serine on oxidative stress markers in the kidney of streptozotocin-induced diabetic mice. Amino Acids 55, 799–806 (2023). https://doi.org/10.1007/s00726-023-03270-9
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DOI: https://doi.org/10.1007/s00726-023-03270-9