Original Research Articles

Ameliorative Effects of D-Ribose-L-Cysteine on Hematological Indices and Metabolic Intermediates in Diabetic Male Wistar Rats

Authors
  • Happy Isibor

    Author
  • Anthony Taghogho Eduviere

    Author
  • Benneth Ben-Azu

    Author
  • Celestine Ogheneruro Akpovwre

    Author
Abstract

Background: Type 2 diabetes mellitus (T2DM) is a chronic disorder characterized by hyperglycemia, insulin resistance, oxidative stress, and progressive β-cell dysfunction. Hematological parameters and metabolic intermediates often reflect systemic inflammation, immune competence, mitochondrial activity, and redox balance, all of which are perturbed in diabetes. This study evaluated the effects of D-ribose-L-cysteine (DRLC), a glutathione precursor, on hematological indices and selected intermediates of energy metabolism in male Wistar rats exposed to a High-Fat Diet (HFD) and Streptozotocin (STZ) (HFD+STZ).

Methods: Animals were randomly divided into control, HFD+STZ, HFD+STZ+DRLC (150 and 300 mg/kg), and HFD+STZ+metformin (100 mg/kg) groups. Treatments were administered orally for 28 days. Hematological indices (White Blood Cells (WBC), Lymphocytes (LYM), Hemoglobin (Hb), Red Blood Cells (RBCs), Mean Corpuscular Volume (MCV), Mean Corpuscular Hemoglobin Concentration (MCHC), and metabolic intermediates (pyruvate, succinate, lactate) together with Malate Dehydrogenase (MDH) activity were assessed.

Results: The HFD+STZ group developed significant leukocytosis, lymphocytosis, anemia, elevated MCV, reduced pyruvate and succinate, increased lactate levels, and altered MDH activity compared to controls (p<0.05). DRLC administration significantly reversed these alterations in a dose-dependent manner, comparable to metformin. DRLC improved red blood cell integrity, enhanced hemoglobin levels, normalized energy metabolites, and modulated MDH activity, suggesting potent antioxidant and hemato-protective actions mediated through glutathione - dependent pathways.

Conclusion: DRLC effectively ameliorated hematological and mitochondrial derangements in diabetic rats, highlighting its therapeutic potential in mitigating diabetes-associated complications.

Keywords: D-Ribose-L-Cysteine, Hematological Indices, Energy Metabolism Intermediates, Streptozotocin -Induced Diabetes, High-Fat Diet

References

1. Adedeji AO, Orisadiran PK. Effects of D-ribose-L-cysteine on lipid profile, atherogenic index and infertility in streptozotocin-induced male diabetic Wistar rats. Asian J Immunol. 2020; 3(1): 11–22.

2. Aderemi AS, Dare OO, Akomaye AJ. Modulating role of D-ribose-L-cysteine on oxidative stress in streptozoto-cin-induced diabetes on plasma lipoprotein, oxidative status, spermatogenesis and steroidogenesis in male Wistar rats. Curr Res Diabetes Obes J. 2018; 9: 55–61. DOI: https://doi.org/10.19080/CRDOJ.2018.09.555760

3. Adelakun SA, Ogunlade B, Fidelis OP, Ajao AA. Nutritional supplementation of D-ribose-L-cysteine suppresses oxid-ative stress, spermatogenesis and steroidogenesis recovery in rats exposed to mercury chloride: histomorphometry and biochemical evidence. Endocrinol Metab Sci. 2021; 4: 100105. DOI: https://doi.org/10.1016/j.endmts.2021.100105

4. Ahmed MJ, Ali O, Ahmed A, Omar W, Ahmed K. The effect of cardiovascular–kidney–metabolic disease on pulse pressure in patients with type II diabetes. J Curr Cardiol. 2025; 3(1): 25–31. DOI: https://doi.org/10.4103/JCC.JCC_2_25

5. Akay F, İnceören N, Nas C, Yokuş B, Kızıl G, Kızıl M. Fructose-derived glycation and immune function: Effects on antigen binding in human IgG and lymphocytes. Arch Biochem Biophys. 2025; 765: 110315. DOI: https://doi.org/10.1016/j.abb.2025.110315

6. Bénit P, Goncalves J, El Khoury R, Rak M, Favier J, Gimenez-Roqueplo AP, Rustin P. Succinate dehydrogenase, succi-nate, and superoxides: a genetic, epigenetic, metabolic, environmental explosive crossroad. Biomedicines. 2022; 10(8): 1788. DOI: https://doi.org/10.3390/biomedicines10081788

7. Black HS. A synopsis of the associations of oxidative stress, ROS, and antioxidants with diabetes mellitus. Antioxidants (Basel). 2022; 11(10): 2003. DOI: https://doi.org/10.3390/antiox11102003

8. Bouillaud F. Inhibition of succinate dehydrogenase by pesticides (SDHIs) and energy metabolism. Int J Mol Sci. 2023; 24(4): 4045. DOI: https://doi.org/10.3390/ijms24044045

9. Bouillaud F, Hammad N, Schwartz L. Warburg effect, glutamine, succinate, alanine, when oxygen matters. Biology (Basel). 2021; 10(10): 1000. DOI: https://doi.org/10.3390/biology10101000

10. Brito AKDS, da Silva Mendes AV, Acha BT, da Silva Santos Oliveira AS, Macedo JL, Cruzio AS, Prianti MG, de Abreu RR, Lucarini M, Durazzo A, Martins MCC, Arcanjo DDR. Experimental models of type 2 diabetes mellitus induced by combining hyperlipidemic diet and streptozotocin administration in rats: An integrative review. Biomedicines. 2025; 13(5): 1158. DOI: https://doi.org/10.3390/biomedicines13051158

11. Brishti MA, Vazhappully Francis F, Leo MD. Plasma metabolomic profiling reveals systemic alterations in a mouse model of type 2 diabetes. Metabolites. 2025; 15(9): 564. DOI: https://doi.org/10.3390/metabo15090564

12. Díez SC, de Las Cuevas Allende R, García EC. Anemia of inflammation and iron metabolism in chronic diseases. Rev Clin Esp (Barc). 2024; 224(9): 598–608. DOI: https://doi.org/10.1016/j.rceng.2024.09.002

13. Gaita L, Timar B, Lazar S, Popescu S, Albai O, Braha A, Timar R. The prevalence and characteristics of anemia in Ro-manian patients with type 2 diabetes: A cross-sectional study. J Clin Med. 2024; 13(23): 7306. DOI: https://doi.org/10.3390/jcm13237306

14. Glancy B, Kane DA, Kavazis AN, Goodwin ML, Willis WT, Gladden LB. Mitochondrial lactate metabolism: history and implications for exercise and disease. J Physiol. 2021; 599(3): 863–888. DOI: https://doi.org/10.1113/JP278930

15. Gupta R, Gupta N. Tricarboxylic acid cycle. In: Fundamentals of Bacterial Physiology and Metabolism. Singapore: Springer; 2021. p. 327–346. DOI: https://doi.org/10.1007/978-981-16-0723-3_12

16. Hacioglu C, Kar F, Kara Y, Yucel E, Donmez DB, Sentürk H, Kanbak G. Comparative effects of metformin and Cistus laurifolius extract in streptozotocin-induced diabetic rats: oxidative, inflammatory, apoptotic and histopathological analyses. Environ Sci Pollut Res Int. 2021; 28(41): 57888–57901. DOI: https://doi.org/10.1007/s11356-021-14780-y

17. Hamdy N, Abdel-Gabbar M, Sakr HI, Gaber SS, Kandeil M, Abdel Aziz AM, Ahmed OM. Anti-diabetic, lipidemic and pro-inflammatory effects of oral hypoglycemics in obese T2DM patients. Egypt J Chem. 2025; 68(4): 91–101.

18. Isibor H, Ajayi AM, Ben-Azu B, Omeiza NA, Ademola AP, Umukoro S. D-ribose-L-cysteine reduces oxidative stress and inflammatory cytokines to mitigate liver damage and memory decline induced by copper sulfate in mice. J Trace Elem Med Biol. 2022; 73: 127001. DOI: https://doi.org/10.1016/j.jtemb.2022.127001

19. Kankaya S, Yavuz F, Tari A, Aygun AB, Gunes EG, Kanat BB, Ulugerger Avci G, Yavuzer H, Dincer Y. Gluta-thione-related antioxidant defence, DNA damage and DNA repair in post-COVID conditions. Mutagenesis. 2023; 38(4): 216–226. DOI: https://doi.org/10.1093/mutage/gead021

20. Lavanya N. Relationship between neutrophil–lymphocyte ratio and insulin resistance in type 2 diabetes mellitus pa-tients [dissertation]. Rajiv Gandhi University of Health Sciences; 2019.

21. Lee H, Kim MJ, Lee IK, Hong CW, Jeon JH. Impact of hyperglycemia on immune cell function: A comprehensive re-view. Diabetol Int. 2024; 15(4): 745–760. DOI: https://doi.org/10.1007/s13340-024-00741-6

22. Li S, Wang J, Xiao Y, Zhang L, Fang J, Yang N, Zhang Z, Nasser MI, Qin H. D-ribose: Potential clinical applications in congestive heart failure and diabetes. Exp Ther Med. 2021; 21(5): 496. DOI: https://doi.org/10.3892/etm.2021.9927

23. Lu C, Zhao H, Liu Y, Yang Z, Yao H, Liu T, Gou T, Wang L, Zhang J, Tian Y, Yang Y, Zhang H. Novel role of SIRT1 in endocrine and metabolic diseases. Int J Biol Sci. 2023; 19(2): 484–501. DOI: https://doi.org/10.7150/ijbs.78654

24. Ossai NR, Ojieh AE, Nwangwa EK, Nwogueze BC. Attenuating potential of modified diets on testicular inflammatory biomarkers in streptozotocin-induced diabetic Wistar rats. Pak Heart J. 2024; 57(1): 297–318.

25. Ma F, Yu W. Roles of lactate and lactylation in mitochondrial dysfunction-related diseases. Int J Mol Sci. 2025; 26(15): 7149. DOI: https://doi.org/10.3390/ijms26157149

26. Malaguarnera M, Cauli O, Cabrera-Pastor A. Obesity and adipose-derived extracellular vesicles: implications for metabolic regulation. Biomolecules. 2025; 15(2): 231. DOI: https://doi.org/10.3390/biom15020231

27. Matboli M, Al-Amodi HS, Khaled A, Khaled R, Roushdy MMS, Ali M, Diab GI, Elnagar MF, Elmansy RA, TAhmed HH, Ahmed EME, Elzoghby DMA, M Kamel HF, Farag MF, ELsawi HA, Farid LM, Abouelkhair MB, Habib EK, Fikry H, Saleh LA, Aboughaleb IH. Machine learning models for predicting therapeutic targets in type 2 diabetes. Front Endocrinol (Lausanne). 2024; 15: 1384984. DOI: https://doi.org/10.3389/fendo.2024.1384984

28. Moorthy R, Arokiasamy J, Suresh Kumar J, Sankar S. Mitochria and diabetes: insights and potential therapies. Expert Rev Endocrinol Metab. 2024; 19(2): 141–154. DOI: https://doi.org/10.1080/17446651.2024.2307526

29. Newsholme P, Keane KN, Carlessi R, Cruzat V. Oxidative stress pathways in pancreatic β-cells and insulin-sensitive tissues. Am J Physiol Cell Physiol. 2019; 317(3): C420–C433. DOI: https://doi.org/10.1152/ajpcell.00141.2019

30. Obeagu EI. Red blood cells as biomarkers in complications of diabetes mellitus. Medicine (Baltimore). 2024; 103(8): e37265. DOI: https://doi.org/10.1097/MD.0000000000037265

31. Obukohwo OM, Falajiki YF, Ohwin PE, Mok MO, Ajayi AF. Medicinal applications of D-ribose-L-cysteine in car-dio-metabolic disorders: A review. Eur J Med Chem Rep. 2024; 11: 100153. DOI: https://doi.org/10.1016/j.ejmcr.2024.100153

32. Ojetola AA, Adeyemi WJ, David UE, Ajibade TO, Adejumobi OA, Omobowale TO, Oyagbemi AA, Fasanmade AA. D-ribose-L-cysteine prevents oxidative stress and cardiometabolic syndrome in rats. Biomed Pharmacother. 2021; 142: 112017. DOI: https://doi.org/10.1016/j.biopha.2021.112017

33. Ziqubu K, Mazibuko-Mbeje SE, Mthembu SX, Mabhida SE, Jack BU, Nyambuya TM, Nkambule BB, Basson AK, Tiano L, Dludla PV. Anti-obesity effects of metformin: a scoping review. Int J Mol Sci. 2023; 24(3): 2227. DOI: https://doi.org/10.3390/ijms24032227

34. Ojetola AA, Asiwe JN, Adeyemi WJ, Ogundipe DJ, Fasanmade AA. Dietary supplementation with D-ribose-L-cysteine prevents hepatic stress in male Wistar rats. Pathophysiology. 2022; 29(4): 631–639. DOI: https://doi.org/10.3390/pathophysiology29040049

35. Onda K, Koyama T, Kobayashi S. Management of iron deficiency anemia in hemodialysis patients. Ren Replace Ther. 2021; 7: 9. DOI: https://doi.org/10.1186/s41100-021-00327-x

36. Qasim N, Arif A, Mahmood R. Hyperglycemia enhances ROS and RNS generation in human erythrocytes. Biochem Cell Biol. 2022; 101(1): 64–76. DOI: https://doi.org/10.1139/bcb-2022-0008

37. Rehak L, Giurato L, Meloni M, Panunzi A, Manti GM, Uccioli L. Immune-centric revolution in diabetic foot wound healing. J Clin Med. 2022; 11(3): 889. DOI: https://doi.org/10.3390/jcm11030889

38. Reddy SS, Sarma A. Prevalence of anaemia in patients with type 2 diabetes mellitus. J Clin Diagn Res. 2021; 15(9): OC01–OC04.

39. Riaz A, Asghar S, Shahid S, Tanvir H, Ejaz MH, Akram M. Prevalence of metabolic syndrome and risk factors in diabetes mellitus. Cureus. 2024; 16(3): e55478.

40. Rodríguez-Rodríguez N, Martínez-Jiménez I, García-Ojalvo A, Mendoza-Mari Y, Guillén-Nieto G, Armstrong DG, Berlanga-Acosta J. Wound chronicity, impaired immunity and infection in diabetic patients. MEDICC Rev. 2022; 24(1): 44–58. DOI: https://doi.org/10.37757/MR2021.V23.N3.8

41. Roy B. Pathophysiological mechanisms of diabetes-induced complications: Role of oxidative stress. Med Sci (Basel). 2025; 13(3): 87. DOI: https://doi.org/10.3390/medsci13030087

42. Song H, Lu J, Zhang Y, Shen X. Wheat germ peptide ameliorates hyperglycemia and hyperlipidemia in diabetic rats. Chem Biodivers. 2025; e202402446.

43. Zhang T, Zhou L, Makarczyk MJ, Feng P, Zhang J. Anti-aging mechanism of metformin. Molecules. 2025; 30(4): 816. DOI: https://doi.org/10.3390/molecules30040816

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20-12-2025
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Original Research Articles

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