Effect of lycopene and metformin combination on phagocytosis, glycemic control, and oxidative stress in rats with type 2 diabetes
DOI:
https://doi.org/10.13181/mji.oa.236774Keywords:
glycemic control, lycopene, metformin, oxidative stress, phagocytosisAbstract
BACKGROUND Hyperglycemia and oxidative stress cause phagocytosis dysfunction in patients with diabetes. A combination of lycopene and metformin can reduce oxidative stress and blood glucose. This study aimed to determine the effect of combined lycopene and metformin on phagocytosis function, glycated hemoglobin A1c (HbA1c), nitric oxide (NO), reactive oxygen species (ROS), and advanced glycation end products (AGEs).
METHODS A randomized controlled study was conducted in rats at the Center for Food and Nutrition Studies, Universitas Gadjah Mada, Yogyakarta, Indonesia, from August to September 2022. 30 rats were divided into control (n = 5) and type 2 diabetes mellitus (T2DM) (n = 25) groups. Rats in the T2DM group were induced by a high-fat diet combined with streptozotocin-nicotinamide. The 25 rats were then divided into five subgroups: 1 ml coconut oil (DM), 250 mg/kg metformin in 1 ml coconut oil (DMet), 250 mg/kg metformin + 10 mg/kg lycopene in 1 ml coconut oil (DML-10), 250 mg/kg metformin + 20 mg/kg lycopene in 1 ml coconut oil (DML-20), and 250 mg/kg metformin + 40 mg/kg lycopene in 1 ml coconut oil (DML-40). Treatments were administered daily for 4 weeks. The macrophage phagocytosis index (PI), HbA1c levels, ROS, NO, and AGEs serum were evaluated.
RESULTS There was a significant difference in the PI, HbA1c, NO, ROS, and AGEs between the groups (p<0.001). The DML-20 and DML-40 groups had significantly increased PI and decreased NO, ROS, and AGEs levels than metformin alone (p<0.05).
CONCLUSIONS Lycopene combined with metformin could improve phagocytosis function, glycemic control, and oxidative stress.
Downloads
References
Insuela D, Coutinho D, Martins M, Ferrero M, Carvalho V. Neutrophil function impairment is a host susceptibility factor to bacterial infection in diabetes. Cells of the Immune System. IntechOpen; 2020. https://doi.org/10.5772/intechopen.86600
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(3):666-74. https://doi.org/10.1080/1828051X.2017.1401438
Pavlou S, Lindsay J, Ingram R, Xu H, Chen M. Sustained high glucose exposure sensitizes macrophage responses to cytokine stimuli but reduces their phagocytic activity. BMC Immunol. 2018;19(1):24. https://doi.org/10.1186/s12865-018-0261-0
Wang R, Sheng M, Shi F, Zhao Y, Zhao L, Wu J, et al. Dysfunctional phagocytosis capacity, granulocyte recruitment and inflammatory factor secretion of Kupffer cells in diabetes mellitus reversed by lidocaine. Diabetes Metab Syndr Obes. 2018;11:827-34. https://doi.org/10.2147/DMSO.S186695
Lecube A, Pachón G, Petriz J, Hernández C, Simó R. Phagocytic activity is impaired in type 2 diabetes mellitus and increases after metabolic improvement. PLoS One. 2011;6(8):e23366. https://doi.org/10.1371/journal.pone.0023366
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(10):ofz358. https://doi.org/10.1093/ofid/ofz358
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(1):e3064. https://doi.org/10.1002/dmrr.3064
Berezin A. Metabolic memory phenomenon in diabetes mellitus: achieving and perspectives. Diabetes Metab Syndr Clin Res Rev. 2016;10(2):S176-83. https://doi.org/10.1016/j.dsx.2016.03.016
Adela R, Nethi SK, Bagul PK, Barui AK, Mattapally S, Kuncha M, et al. Hyperglycaemia enhances nitric oxide production in diabetes: a study from South Indian patients. PLoS One. 2015;10(4):e0125270. https://doi.org/10.1371/journal.pone.0125270
Ridzuan N, John CM, Sandrasaigaran P, Maqbool M, Liew LC, Lim J, et al. Preliminary study on overproduction of reactive oxygen species by neutrophils in diabetes mellitus. World J Diabetes. 2016;7(13):271-8. https://doi.org/10.4239/wjd.v7.i13.271
Indyk D, Bronowicka-Szyde?ko A, Gamian A, Kuzan A. Advanced glycation end products and their receptors in serum of patients with type 2 diabetes. Sci Rep. 2021;11(1):1-14. https://doi.org/10.1038/s41598-021-92630-0
American Diabetes Association. Standards of medical care in diabetes-2020 abridged for primary care providers. Clin Diabetes. 2020;38(1):10-38. https://doi.org/10.2337/cd20-as01
Cheng G, Lanza-Jacoby S. Metformin decreases growth of pancreatic cancer cells by decreasing reactive oxygen species: role of NOX4. Biochem Biophys Res Commun. 2015;465(1):41-6. https://doi.org/10.1016/j.bbrc.2020.03.061
Liu Y, Huang C, Ceng C, Zhan H, Zheng D, Han W. Metformin enhances nitric oxide production and diminishes Rho kinase activity in rats with hyperlipidemia. Lipids Health Dis. 2014;13(1):115. https://doi.org/10.1186/s12944-018-0755-z
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. 2020;13:3117-35. https://doi.org/10.2147/DMSO.S265944
Saeed NM, Mansour AM, Allam S. Lycopene induces insulin signaling and alleviates fibrosis in experimental model of non-alcoholic fatty liver disease in rats. PharmaNutrition. 2020;14:100225. https://doi.org/10.1016/j.phanu.2020.100225
Guerra BA, Otton R. Impact of the carotenoid astaxanthin on phagocytic capacity and ROS/RNS production of human neutrophils treated with free fatty acids and high glucose. Int Immunopharmacol. 2011;11(12):2220-6. https://doi.org/10.1016/j.intimp.2011.10.004
Tabrez S, Al-Shali KZ, Ahmad S. Lycopene powers the inhibition of glycation-induced diabetic nephropathy: a novel approach to halt the AGE-RAGE axis menace. Biofactors. 2015;41(5):372-81. https://doi.org/10.1002/biof.1238
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(1):1059-65. https://doi.org/10.1080/07853890.2021.1943515
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(2):119-24.
Ghasemi A, Khalifi S, Jedi S. Streptozotocin-nicotinamide-induced rat model of type 2 diabetes (review). Acta Physiol Hung. 2014;101(4):408-20. https://doi.org/10.1556/APhysiol.101.2014.4.2
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):805. https://doi.org/10.1186/s13104-019-4841-8
Tang Q, Su YW, Xian CJ. Determining oxidative damage by lipid peroxidation assay in rat serum. Bio Protoc. 2019;9(12):e3263. https://doi.org/10.21769/BioProtoc.3263
Wahdaningsih S, Wahyuono S, Riyanto S, Murwanti R. In vitro test of macrophage phagocytic activity of extracts and fractions of red dragon fruit peel [Hylocereus polyrhizus (F.A.C.Weber) Britton and Rose]. Dhaka Univ J Pharm Sci. 2018;17(2):161-5. https://doi.org/10.3329/dujps.v17i2.39171
Durairajanayagam D, Agarwal A, Ong C, Prashast P. Lycopene and male infertility. Asian J Androl. 2014;16(3):420-5. 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 (Basel). 2020;9(8):706. https://doi.org/10.3390/antiox9080706
Published
How to Cite
Issue
Section
License
Authors who publish with Medical Journal of Indonesia agree to the following terms:
- Authors retain copyright and grant Medical Journal of Indonesia right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial License that allows others to remix, adapt, build upon the work non-commercially with an acknowledgment of the work’s authorship and initial publication in Medical Journal of Indonesia.
- Authors are permitted to copy and redistribute the journal's published version of the work non-commercially (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in Medical Journal of Indonesia.
