Metformin is the approved medication for managing global health issues concerning type 2 diabetes mellitus (T2DM). Using natural bioactive compounds as an alternative therapy is crucial to managing several metabolic diseases. Therefore, due to recent limited studies that detected the role of bee venom (BV) in improving diabetic conditions in Iraq, the current study was designed to identify the potential therapeutic role of BV and metformin in diabetic mice. Twenty male mice (Balb/c) aged about 60 days with an average weight of 26.55±2.70 g were randomly divided into four groups (n=5). The animals were placed in plastic cages for acclimatization for one week of access to food and water ad libitum. Overnight fasting was applied to 15 mice which were then injected with 95 mg/kg body weight of prepared alloxan. The mice were supplemented with glucose fluid for 3 days. On day 4, the blood was collected from the tail to measure the circulating glucose level. When blood glucose levels exceed 200 mg/dl, the animals are considered diabetic. After induction of diabetes, the animals were divided as follows: Control group: included five mice that were not subjected to diabetes induction; the animals in this group did not receive any medications. Diabetic group: including five mice confirmed with diabetes without receiving any treatments. Metformin group: including five diabetic mice exposed to a single oral dose of 150 mg/kg of metformin for 30 days. Bee Venom group: including five diabetic mice exposed to a single intraperitoneal dose of 1 mg/kg Bee Venom for 30 days. After 30 days of treatment, blood was drained, and serum was obtained to detect the levels of glucose, insulin, TNFα, IL6, and IL10 by using precise enzyme-linked immunosorbent assay (ELIZA) kits. Also, the pancreas was collected from all mice for histopathological investigation. The result displayed significantly elevated glucose concentration in diabetic mice, while metformin and BV significantly reversed these increases. A significant decline in insulin concentration was seen in diabetic mice, whereas metformin and BV significantly enhanced this reduction in insulin concentration. Furthermore, mice treated with alloxan exhibited remarkable increases in TNFα and IL6 compared to control mice, while supplemented metformin and BV significantly reduced these high concentrations. Moreover, the level of IL10 markedly declined in diabetic mice, which was reversed significantly in response to metformin and BV. Histological detection of the pancreas in diabetic mice showed significant changes in the shape and size of islets associated with the arrangement and number of beta cells with a reduction of islets covering connective tissue. Metformin slightly restored these alterations; however, significant and remarkable restoring of histological changing was promoted by BV. Thus, BV could be a potential agent for managing metabolic disorders including diabetes. |
- Alam S, Hasan M, Neaz S, Hussain N, Hossain M, Rahman T. Diabetes Mellitus: insights from epidemiology, biochemistry, risk factors, diagnosis, complications and comprehensive management. Diabetology. 2021;2(2):36-50.
- Ogurtsova K, Guariguata L, Barengo NC, Ruiz PL-D, Sacre JW, Karuranga S, et al. IDF diabetes Atlas: Global estimates of undiagnosed diabetes in adults for 2021. Diabetes Res Clin Pract. 2022;183:109118.
- Merdzo I, Rutkai I, Sure VN, McNulty CA, Katakam PV, Busija DW. Impaired mitochondrial respiration in large cerebral arteries of rats with type 2 diabetes. J Vasc Res. 2017;54(1):1-12.
- JJ Al-Shaeli S, M Ethaeb A, AN Al-Zaidi E. Serological and Histological Estimation of the Effect of Honeybee Venom on Pancreas and Liver in Diabetic Mice. Arch Razi Inst. 2022.
- Rupashri S, Gheena S. Recent advances in diabetes research. Res J Pharm Technol. 2016;9(10):1806.
- Isoda K, Young JL, Zirlik A, MacFarlane LA, Tsuboi N, Gerdes N, et al. Metformin inhibits proinflammatory responses and nuclear factor-κB in human vascular wall cells. Arterioscler Thromb Vasc Biol. 2006;26(3):611-7.
- Chen W, Liu X, Ye S. Effects of metformin on blood and urine pro-inflammatory mediators in patients with type 2 diabetes. J Inflamm. 2016;13(1):1-6.
- Aljofan M, Gaipov A. Metformin: a stroke of luck. 2019.
- Kurek-Górecka A, Komosinska-Vassev K, Rzepecka-Stojko A, Olczyk P. Bee venom in wound healing. Molecules. 2020;26(1):148.
- SAMANCI T, Kekeçoğlu M. Comparison of commercial and Anatolian bee venom in terms of chemical composition. Uludag Aricilik Derg. 2019;19(1):61-8.
- Zolfagharian H, Mohajeri M, Babaie M. Bee venom (Apis Mellifera) an effective potential alternative to gentamicin for specific bacteria strains: Bee venom an effective potential for bacteria. J Pharmacopunct. 2016;19(3):225.
- Lim HN, Baek SB, Jung HJ. Bee venom and its peptide component melittin suppress growth and migration of melanoma cells via inhibition of PI3K/AKT/mTOR and MAPK pathways. Molecules. 2019;24(5):929.
- AL-Shaeli SJ, Ethaeb AM. Decaffeinated green tea extract regulates glucose metabolism in insulin-sensitive cell lines. Res J Pharm Technol. 2019;12(6):2814-23.
- Herzig V. Animal Venoms—Curse or Cure? : Multidisciplinary Digital Publishing Institute; 2021. p. 413.
- Chen N, Xu S, Zhang Y, Wang F. Animal protein toxins: origins and therapeutic applications. Biophys Rep. 2018;4(5):233-42.
- Amatya R, Park T, Hwang S, Yang J, Lee Y, Cheong H, et al. Drug Delivery Strategies for Enhancing the Therapeutic Efficacy of Toxin-Derived Anti-Diabetic Peptides. Toxins. 2020;12(5):313.
- Berbudi A, Rahmadika N, Tjahjadi AI, Ruslami R. Type 2 diabetes and its impact on the immune system. Curr Diabetes Rev. 2020;16(5):442.
- Boersma GJ, Heurling K, Pereira MJ, Johansson E, Lubberink M, Katsogiannos P, et al. Glucose uptake in muscle, visceral adipose tissue, and brain strongly predict whole-body insulin resistance in the development of type 2 diabetes. Diabetes. 2018;67(1).
- Dludla PV, Nkambule BB, Mazibuko-Mbeje SE, Nyambuya TM, Mxinwa V, Mokgalaboni K, et al. Adipokines as a therapeutic target by metformin to improve metabolic function: A systematic review of randomized controlled trials. Pharmacol Res. 2021;163:105219.
- Hassan AK, El-kotby DA, Tawfik MM, Badr RE, Bahgat IM. Antidiabetic effect of the Egyptian honey bee (Apis mellifera) venom in alloxan-induced diabetic rats. J Basic appl zool. 2019;80(1):1-9.
- Mousavi SM, Imani S, Haghighi S, Mousavi SE, Karimi A. Effect of Iranian honey bee (Apis mellifera) venom on blood glucose and insulin in diabetic rats. J Arthropod Borne Dis. 2012;6(2):136.
- Zahran F, Mohamed A, Zein N. Bee venom attenuates degenerative effects of diabetes associated with hyperlipidemia in rats. Biochem Lett. 2021;17(1):77-107.
- Charlton A, Garzarella J, Jandeleit-Dahm KA, Jha JC. Oxidative stress and inflammation in renal and cardiovascular complications of diabetes. Biology. 2020;10(1):18.
- Degirmenci I, Ozbayer C, Kebapci MN, Kurt H, Colak E, Gunes HV. Common variants of genes encoding TLR4 and TLR4 pathway members TIRAP and IRAK1 are effective on MCP1, IL6, IL1β, and TNFα levels in type 2 diabetes and insulin resistance. Inflamm Res. 2019;68(9):801-14.
- Bare Y, Marhendra APW, Sasase T, Fatchiyah F. Differential expression of IL-10 gene and protein in target tissues of Rattus norvegicus Strain Wistar model type 2 Diabetes Mellitus (T2DM). Acta Inform Med. 2018;26(2):87.
- Hasanpour Dehkordi A, Abbaszadeh A, Mir S, Hasanvand A. Metformin and its anti-inflammatory and anti-oxidative effects; new concepts. J Renal Inj Prev. 2019.
- El Adham EK, Hassan AI, A Dawoud M. Evaluating the role of propolis and bee venom on the oxidative stress induced by gamma rays in rats. Sci Rep. 2022;12(1):1-22.
- Hacioglu C, Kar F, Kara Y, Yucel E, Donmez DB, Sentürk H, et al. Comparative effects of metformin and Cistus laurifolius L. extract in streptozotocin-induced diabetic rat model: oxidative, inflammatory, apoptotic, and histopathological analyzes. Environ Sci Pollut Res. 2021;28(41):57888-901.
- Elkotby D, Hassan AK, Emad R, Bahgat I. Histological changes in islets of Langerhans of pancreas in alloxan-induced diabetic rats following Egyptian honey bee venom treatments. Int J Pure Appl Zool. 2018;6(1):1-6.
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