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Medina Sianturi Neni Susilaningsih Heri Nugroho Maria Suryani

Abstract

In patients with type 2 diabetes mellitus (T2DM), both innate and acquired immunity are weakened by hyperglycemia. Lycopene is one of the hydrocarbon carotenoids that has been widely studied for its powerful antioxidant and anti-inflammatory properties, furthermore act as hypoglycemic and immunomodulator. Herein, we investigated the effect of lycopene and metformin combination on fasting blood glucose (FBG) and neutrophil counts. The rats were divided randomly into six groups, each containing five rats. Group 1 consisted of normal rats (N) and group 2, T2DM (DM) rats, which were administered 0.5 mL of coconut oil; group 3 T2DM rats were administered 250 mg/kg of metformin in 0.5 mL of coconut oil; groups  4,5 and 6 rats were administered a combination of metformin 250 mg/kg with 10 mg/kg (DML-10), 20 mg/kg (DML-20) and 40 mg/kg (DML-40) of lycopene in 0.5 mL of coconut oil, respectively. Treatment was administered every day for 28 days. A model of T2DM rats was induced by a high-fat diet for two weeks combined with streptozotocin–nicotinamide. Data were analyzed with a one-way ANOVA test followed by the least significant difference (LSD) test. There were significant differences in FBG levels and the number of neutrophils in all groups. Lycopene combined with metformin had lower FBG concentrations and higher neutrophil counts compared to metformin monotherapy (p<0.001), and these observations were dose-dependent. Lycopene combined with metformin can improve blood glucose and neutrophil counts in rats with diabetes. The highest effect was observed in combination with lycopene at a dose of 40 mg/kg and metformin at a dose of 250 mg/kg.

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How to Cite
Sianturi, M., Susilaningsih, N., Nugroho, H. and Suryani, M. (2023) “Lycopene Improves the Metformin Effects on Blood Glucose and Neutrophil Counts in Type 2 Diabetic Rats”, Indonesian Journal of Medical Laboratory Science and Technology, 5(1), pp. 80–89. doi: 10.33086/ijmlst.v5i1.3865.
Section
Articles
Blood Glucose, Lycopene, Metformin, Neutrophil, T2DM

References

Eze ED, Afodun AM, Kasolo J, Kasozi KI. Lycopene improves on basic hematological and immunological parameters in diabetes mellitus. BMC Res Notes 2019;12:1–7. DOI: 10.1186/s13104-019-4841-8. DOI: https://doi.org/10.1186/s13104-019-4841-8

Fachinello MR, Fernandes NLM, de Souto ER, dos Santos TC, da Costa AER, Pozza PC. Lycopene affects the immune responses of finishing pigs. Ital J Anim Sci 2018;17:666–74. DOI: 10.1080/1828051X.2017.140143. DOI: https://doi.org/10.1080/1828051X.2017.1401438

Insuela D, Coutinho D, Martins M, Ferrero M, Carvalho V. Neutrophil function impairment is a host susceptibility factor to bacterial infection in diabetes. Cells Immune Syst 2020:1–22. DOI: 10.5772/intechopen.86600. DOI: https://doi.org/10.5772/intechopen.86600

Tessaro FHG, Ayala TS, Nolasco EL, Bella LM MJ. Insulin influences LPS-Induced TNF-α and IL-6 release through distinct pathways in mouse macrophages from different compartments. Cell Physiol Biochem 2017;42:2093–104. DOI: 10.1159/000479904. DOI: https://doi.org/10.1159/000479904

Jafar N, Edriss H, Nugent K. The effect of short-term hyperglycemia on the innate immune system. Am J Med Sci 2016;351:201–11. DOI: 10.1016/j.amjms.2015.11.011. DOI: https://doi.org/10.1016/j.amjms.2015.11.011

Huang J, Xiao Y, Zheng P, Zhou W, Wang Y, Huang G, et al. Distinct neutrophil counts and functions in newly diagnosed type 1 diabetes, latent autoimmune diabetes in adults, and type 2 diabetes. Diabetes Metab Res Rev 2019;35. DOI: 10.1002/dmrr.3064. DOI: https://doi.org/10.1002/dmrr.3064

Grossmannm V, Schmitt VH, Zeller T, Panova-Noeva M, Schulz A, Laubert-Reh D, et al. Profile of the immune and inflammatory response in individuals with prediabetes and type 2 diabetes. Diabetes Care 2015;38:1356–64. DOI: 10.2337/dc14-3008. DOI: https://doi.org/10.2337/dc14-3008

Berbudi A, Rahmadika N, Tjahjadi AI, Ruslami R. Type 2 diabetes and its impact on the immune system. Curr Diabetes Rev 2019;16:442–9. DOI: 10.2174/1573399815666191024085838. DOI: https://doi.org/10.2174/1573399815666191024085838

Chang CH, Wang JL, Wu LC, Chuang LM, Lin HH. Diabetes, glycemic control, and risk of infection morbidity and mortality: A cohort study. Open Forum Infect Dis 2019;6:1–12. DOI: 10.1093/ofid/ofz358. DOI: https://doi.org/10.1093/ofid/ofz358

Zheng Z, Yin Y, Lu R, Jiang Z. Lycopene ameliorated oxidative stress and inflammation in type 2 diabetic rats. J Food Sci 2019;84:1194–200. DOI: 10.1111/1750-3841.14505. DOI: https://doi.org/10.1111/1750-3841.14505

Yin Y, Zheng Z, Jiang Z. Effects of lycopene on metabolism of glycolipid in type 2 diabetic rats. Biomed Pharmacother 2019;109:2070–7. DOI: 10.1016/j.biopha.2018.07.100. DOI: https://doi.org/10.1016/j.biopha.2018.07.100

Leh HE, Mohd Sopian M, Abu Bakar MH, Lee LK. The role of lycopene for the amelioration of glycaemic status and peripheral antioxidant capacity among the Type II diabetes mellitus patients: a case–control study. Ann Med 2021;53:1058–64. DOI: 10.1080/07853890.2021.1943515. DOI: https://doi.org/10.1080/07853890.2021.1943515

Hedayati N, Oskouei Z, Tabeshpour J, Naeini MB. Berberine and lycopene as alternative or add-on therapy to metformin and statins, a review. Eur J Pharmacol 2021;913:174590. DOI: 10.1016/j.ejphar.2021.174590. DOI: https://doi.org/10.1016/j.ejphar.2021.174590

Haribabu T, Divakar K, Goli D. Evaluation of anti-diabetic activity of Lycopene and its synergistic effect with Metformin hydrochloride and Glipizide in Alloxan induced diabetes in rats. Sch Acad J Pharm 2013;2:119–24.

Figueiredo ID, Lima TFO, Inácio MD, Costa MC, Assis RP, Brunetti IL, et al. Lycopene improves the metformin effects on glycemic control and decreases biomarkers of glycoxidative stress in diabetic rats. Diabetes, Metab Syndr Obes Targets Ther 2020;13:3117–35. DOI: 10.2147/DMSO.S265944. DOI: https://doi.org/10.2147/DMSO.S265944

Ghasemi A, Khalifi S, Jedi S. Streptozotocin-nicotinamide-induced rat model of type 2 diabetes (review). Acta Physiol Hung 2014;101:408–20. DOI: 10.1556/APhysiol.101.2014.4.2. DOI: https://doi.org/10.1556/APhysiol.101.2014.4.2

Dhanasekara CS, Nelson A, Spradley M, Wynn A, Robohm-Leavitt C, Shen CL, et al. Effects of consumption of coconut oil or coconut on glycemic control and insulin sensitivity: A systematic review and meta-analysis of interventional trials. Nutr Metab Cardiovasc Dis 2022;32:53–68. DOI: 10.1016/j.numecd.2021.09.014. DOI: https://doi.org/10.1016/j.numecd.2021.09.014

DiaSys. Glucose GOD FS. Diasys Diagnostic Syst 2015:1–6.

Goswami K, Mookherjee S. Comparison between haematological parameters by the Merilyzer Celquant 360 Automated Haematology Analyser and Sysmex Xp-100 Haematology Analyser with the manual methods 2018;5:675–9.

American Diabetes Association. Standards of medical care in diabetes—2020. Diabetes Care 2020;35. DOI: 10.2337/dc12-s011. DOI: https://doi.org/10.2337/dc12-s011

Soelistijo SA et all. Management and Prevention of type 2 diabetes mellitus in adults in Indonesia. [Pengelolaan Dan Pencegahan Diabetes Melitus Tipe 2 Dewasa di Indonesia]. Perkumpulan Endokrinol Indones 2019:133.

Madiraju AK, Qiu Y, Perry RJ, Rahimi Y, Zhang XM, Zhang D, et al. Metformin inhibits gluconeogenesis via a redox-dependent mechanism in vivo. Nat Med 2018;24:1384–94. DOI: 10.1038/s41591-018-0125-4. DOI: https://doi.org/10.1038/s41591-018-0125-4

Moldovan AI, Tigu B, Jula CT, Moldovan CS, Pojar S, Drula R, et al. Lycopene and phycocyanin - biological properties in experimental diabetes: 1. Effects on blood parameters and liver carbohydrates. Stud Univ Babes-Bolyai Biol 2016;61:31–9.

Bhatia N, Singh B, Koul A. Lycopene treatment stalls the onset of experimentally induced hepatocellular carcinoma: a radioisotopic, physiological and biochemical analysis. Hepatoma Res 2018;4:9. DOI: 10.20517/2394-5079.2018.04. DOI: 10.20517/2394-5079.2018.04 DOI: https://doi.org/10.20517/2394-5079.2018.04

Bácsi A, Lucas R, Sütő MI, Szklenár M, Bohn T RR. An immune-shift induced by lycopene; from an eosinophil-dominant type towards an eosinophil/neutrophil-co-dominant type of airway inflammation. Food Funct 2022;13:6534–44. DOI: 10.1039/D2FO00875K. DOI: https://doi.org/10.1039/D2FO00875K

Durairajanayagam D, Agarwal A, Ong C, Prashast P. Lycopene and male infertility. Asian J Androl 2014;16:420–5. DOI: 10.4103/1008-682X.126384. DOI: https://doi.org/10.4103/1008-682X.126384

Imran M, Ghorat F, Ul‐haq I, Ur‐rehman H, Aslam F, Heydari M, et al. Lycopene as a natural antioxidant used to prevent human health disorders. Antioxidants 2020;9:1–27. DOI: 10.3390/antiox9080706. DOI: https://doi.org/10.3390/antiox9080706

Medina Sianturi, Department of Nursing, STIKes Elisabeth, Semarang, Central Java, Indonesia

Neni Susilaningsih, Department of Histology, Faculty of Medicine, Diponegoro University, Semarang, Central Java, Indonesia

Heri Nugroho, Department of Internal Medicine, Faculty of Medicine, Diponegoro University, Semarang, Central Java, Indonesia

Maria Suryani, Department of Nursing, STIKes Elisabeth, Semarang, Central Java, Indonesia