Tác Động Chống Viêm Của Melatonin Trên Chuột Bị Đái Tháo Đường Type 2 Được Kích Thích
Tóm tắt
Giới thiệu: Tình trạng kháng insulin liên quan đến một trạng thái viêm mạn tính, làm tăng nguy cơ gặp phải các biến chứng ở bệnh nhân đái tháo đường type 2 (T2DM). Ngoài tác động theo nhịp sinh học, hormone melatonin do tuyến tùng tiết ra còn được biết đến với tác dụng chống viêm và chống oxy hóa. Melatonin cũng được cho là có ảnh hưởng đến sự tiết insulin. Mục tiêu của nghiên cứu này là khảo sát tác động của melatonin lên viêm ở chuột mắc bệnh đái tháo đường và nghiên cứu sự tham gia có thể có của thụ thể melatonin, MT2. Vật liệu và Phương pháp: Chuột đực Sprague Dawley được chia ngẫu nhiên thành bốn nhóm thí nghiệm (n = 10 mỗi nhóm): (1) nhóm kiểm soát, (2) nhóm đái tháo đường type 2 do streptozotocin/nicotinamide gây ra, (3) nhóm T2DM được điều trị bằng melatonin (500 µg/kg/ngày), và (4) nhóm T2DM được điều trị bằng melatonin (500 µg/kg/ngày trong 6 tuần) và đối kháng thụ thể MT2 chọn lọc luzindole (0.25 g/kg/ngày trong 6 tuần). Mẫu máu được lấy để phân tích các tham số hóa sinh và các mẫu mô (gan, mô mỡ, não) được lấy để thực hiện phân tích miễn dịch mô học (IHC), Western blot (WB), và Q-PCR. Kết quả: Melatonin đã giảm đáng kể nồng độ transaminase gan (AST, ALT), nitơ ure máu (BUN), triglycerid, lipoprotein tỷ trọng rất thấp (VLDL), và cholesterol trong máu của chuột đái tháo đường, trong khi việc điều trị bằng luzindole đã phần nào đảo ngược tác động này đối với lipid. Hơn nữa, mô gan và mô mỡ của các chuột T2DM được điều trị bằng melatonin cho thấy sự biểu hiện thấp hơn của các chỉ số viêm IL-1β, IL-6, TNF-α và NF-κB so với nhóm T2DM không có melatonin. Kết quả cũng chỉ ra rằng thụ thể MT2 ít nhất một phần tham gia vào các tác dụng bảo vệ của melatonin. Kết luận: Kết quả của chúng tôi gợi ý rằng melatonin thể hiện tác dụng chống viêm liên quan đến các mô khác nhau ở chuột đái tháo đường type 2.
Từ khóa
Tài liệu tham khảo
Mathers, C.D., and Loncar, D. (2006). Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med., 3.
Scheen, 2014, Combating the dual burden: Therapeutic targeting of common pathways in obesity and type 2 diabetes, Lancet Diabetes Endocrinol., 2, 911, 10.1016/S2213-8587(14)70004-X
Mishra, 2011, Level of serum IL-12 and its correlation with endothelial dysfunction, insulin resistance, proinflammatory cytokines and lipid profile in newly diagnosed type 2 diabetes, Diabetes Res. Clin. Pract., 94, 255, 10.1016/j.diabres.2011.07.037
Chen, 2017, Hypothalamic Insulin Resistance in Obesity: Effects on Glucose Homeostasis, Neuroendocrinology, 104, 364, 10.1159/000455865
Peraldi, 1998, TNF-alpha and insulin resistance: Summary and future prospects, Mol. Cell. Biochem., 182, 169, 10.1023/A:1006865715292
Morris, 2015, Minireview: Emerging Concepts in Islet Macrophage Biology in Type 2 Diabetes, Mol. Endocrinol., 29, 946, 10.1210/me.2014-1393
Larsen, 2007, Interleukin-1-receptor antagonist in type 2 diabetes mellitus, N. Engl. J. Med., 356, 1517, 10.1056/NEJMoa065213
Grivas, 2007, Melatonin the "light of night" in human biology and adolescent idiopathic scoliosis, Scoliosis, 2, 6, 10.1186/1748-7161-2-6
Esposito, 2010, Antiinflammatory activity of melatonin in central nervous system, Curr. Neuropharmacol., 8, 228, 10.2174/157015910792246155
2013, Therapeutic applications of melatonin, Ther. Adv. Endocrinol. Metab., 4, 13, 10.1177/2042018813476084
MacDonald, I.J., Huang, C.C., Liu, S.C., and Tang, C.H. (2020). Reconsidering the Role of Melatonin in Rheumatoid Arthritis. Int. J. Mol. Sci., 21.
Chen, 2018, Melatonin attenuated inflammatory reaction by inhibiting the activation of p38 and NFkappaB in taurocholateinduced acute pancreatitis, Mol. Med. Rep., 17, 5934
Farez, 2016, Anti-inflammatory effects of melatonin in multiple sclerosis, Bioessays, 38, 1016, 10.1002/bies.201600018
Shang, 2016, Protective effect of melatonin on myenteric neuron damage in experimental colitis in rats, Fundam. Clin. Pharmacol., 30, 117, 10.1111/fcp.12181
Cuesta, 2010, Melatonin improves inflammation processes in liver of senescence-accelerated prone male mice (SAMP8), Exp. Gerontol., 45, 950, 10.1016/j.exger.2010.08.016
Hu, 2009, Melatonin protects against alcoholic liver injury by attenuating oxidative stress, inflammatory response, and apoptosis, Eur. J. Pharmacol., 616, 287, 10.1016/j.ejphar.2009.06.044
Laste, 2012, Melatonin administration reduces inflammatory pain in rats, J. Pain Res., 5, 359
Patel, R., Parmar, N., Palit, S.P., Rathwa, N., Ramachandran, A.V., and Begum, R. (2022). Diabetes mellitus and melatonin: Where are we?. Biochimie.
Peschke, 2000, Evidence for a melatonin receptor within pancreatic islets of neonate rats: Functional, autoradiographic, and molecular investigations, J. Pineal Res., 28, 156, 10.1034/j.1600-079X.2001.280305.x
Picinato, 2002, Melatonin inhibits insulin secretion and decreases PKA levels without interfering with glucose metabolism in rat pancreatic islets, J. Pineal Res., 33, 156, 10.1034/j.1600-079X.2002.02903.x
Rasmussen, 1999, Daily melatonin administration at middle age suppresses male rat visceral fat, plasma leptin, and plasma insulin to youthful levels, Endocrinology, 140, 1009, 10.1210/endo.140.2.6674
Mitton, 2000, Daily melatonin administration to middle-aged male rats suppresses body weight, intraabdominal adiposity, and plasma leptin and insulin independent of food intake and total body fat, Endocrinology, 141, 487, 10.1210/endo.141.2.7311
Peschke, 2007, Melatonin and type 2 diabetes—A possible link?, J. Pineal Res., 42, 350, 10.1111/j.1600-079X.2007.00426.x
Ekmekcioglu, 2006, Melatonin receptors in humans: Biological role and clinical relevance, Biomed. Pharmacother., 60, 97, 10.1016/j.biopha.2006.01.002
Ekmekcioglu, 2003, The melatonin receptor subtype MT2 is present in the human cardiovascular system, J. Pineal Res., 35, 40, 10.1034/j.1600-079X.2003.00051.x
Wongprayoon, 2015, Melatonin attenuates methamphetamine-induced neuroinflammation through the melatonin receptor in the SH-SY5Y cell line, Neurotoxicology, 50, 122, 10.1016/j.neuro.2015.08.008
Söderquist, F., Hellstrom, P., and Cunningham, J.L. (2015). Human gastroenteropancreatic expression of melatonin and its receptors MT1 and MT2. PLoS ONE, 10.
Boutin, 2005, Molecular tools to study melatonin pathways and actions, Trends Pharmacol. Sci., 26, 412, 10.1016/j.tips.2005.06.006
Das, 2017, Melatonin protects against lipid-induced mitochondrial dysfunction in hepatocytes and inhibits stellate cell activation during hepatic fibrosis in mice, J. Pineal Res., 62, e12404, 10.1111/jpi.12404
Ou, T.H., Tung, Y.T., Yang, T.H., and Chien, Y.W. (2019). Melatonin Improves Fatty Liver Syndrome by Inhibiting the Lipogenesis Pathway in Hamsters with High-Fat Diet-Induced Hyperlipidemia. Nutrients, 11.
Hajam, 2019, Melatonin and insulin modulates the cellular biochemistry, histoarchitecture and receptor expression during hepatic injury in diabetic rats, Life Sci., 239, 117046, 10.1016/j.lfs.2019.117046
Cheshchevik, 2011, Corrections by melatonin of liver mitochondrial disorders under diabetes and acute intoxication in rats, Cell Biochem. Funct., 29, 481, 10.1002/cbf.1775
Baydas, 2002, Comparative analysis of the protective effects of melatonin and vitamin E on streptozocin-induced diabetes mellitus, J. Pineal Res., 32, 225, 10.1034/j.1600-079X.2002.01856.x
Laemmli, 1970, Cleavage of structural proteins during the assembly of the head of bacteriophage T4, Nature, 227, 680, 10.1038/227680a0
Koc, 2015, Impaired mitochondrial protein synthesis in head and neck squamous cell carcinoma, Mitochondrion, 24, 113, 10.1016/j.mito.2015.07.123
Zanquetta, 2003, Calorie restriction reduces pinealectomy-induced insulin resistance by improving GLUT4 gene expression and its translocation to the plasma membrane, J. Pineal Res., 35, 141, 10.1034/j.1600-079X.2003.00067.x
Peschke, 2010, New evidence for a role of melatonin in glucose regulation, Best Pract. Res. Clin. Endocrinol. Metab., 24, 829, 10.1016/j.beem.2010.09.001
Peschke, 2006, Diabetic Goto Kakizaki rats as well as type 2 diabetic patients show a decreased diurnal serum melatonin level and an increased pancreatic melatonin-receptor status, J. Pineal Res., 40, 135, 10.1111/j.1600-079X.2005.00287.x
Kor, 2014, Preliminary study: Evaluation of melatonin secretion in children and adolescents with type 1 diabetes mellitus, Indian J. Endocrinol. Metab., 18, 565, 10.4103/2230-8210.137521
Hajam, Y.A., Rai, S., Pandi-Perumal, S.R., Brown, G.M., Reiter, R.J., and Cardinali, D.P. (2021). Coadministration of Melatonin and Insulin Improves Diabetes-Induced Impairment of Rat Kidney Function. Neuroendocrinology.
Abdulwahab, 2021, Melatonin protects the heart and pancreas by improving glucose homeostasis, oxidative stress, inflammation and apoptosis in T2DM-induced rats, Heliyon, 7, e06474, 10.1016/j.heliyon.2021.e06474
Sudnikovich, 2007, Melatonin attenuates metabolic disorders due to streptozotocin-induced diabetes in rats, Eur. J. Pharmacol., 569, 180, 10.1016/j.ejphar.2007.05.018
Li, 2013, Effects of melatonin on streptozotocin-induced retina neuronal apoptosis in high blood glucose rat, Neurochem. Res., 38, 669, 10.1007/s11064-012-0966-z
Kozakiewic, 2009, Melatonin improves oxidative stress parameters measured in the blood of elderly type 2 diabetic patients, J. Pineal Res., 46, 333, 10.1111/j.1600-079X.2009.00666.x
Sobngwi, 2013, Diabetes mellitus and inflammation, Curr. Diabetes Rep., 13, 435, 10.1007/s11892-013-0375-y
Karstoft, 2016, Exercise and type 2 diabetes: Focus on metabolism and inflammation, Immunol. Cell Biol., 94, 146, 10.1038/icb.2015.101
Amin, 2019, How the association between obesity and inflammation may lead to insulin resistance and cancer, Diabetes Metab. Syndr. Clin. Res. Rev., 13, 1213, 10.1016/j.dsx.2019.01.041
Zhen, 2012, Alterations of peripheral CD4+CD25+Foxp3+ T regulatory cells in mice with STZ-induced diabetes, Cell. Mol. Immunol., 9, 75, 10.1038/cmi.2011.37
Zhang, 2011, Interferon-gamma induced adipose tissue inflammation is linked to endothelial dysfunction in type 2 diabetic mice, Basic Res. Cardiol., 106, 1135, 10.1007/s00395-011-0212-x
Ventre, 1997, Targeted disruption of the tumor necrosis factor-alpha gene: Metabolic consequences in obese and nonobese mice, Diabetes, 46, 1526, 10.2337/diab.46.9.1526
Kaneto, 2004, Possible novel therapy for diabetes with cell-permeable JNK-inhibitory peptide, Nat. Med., 10, 1128, 10.1038/nm1111
Tuncman, 2006, Functional in vivo interactions between JNK1 and JNK2 isoforms in obesity and insulin resistance, Proc. Natl. Acad. Sci. USA, 103, 10741, 10.1073/pnas.0603509103
Donath, 2016, Multiple benefits of targeting inflammation in the treatment of type 2 diabetes, Diabetologia, 59, 679, 10.1007/s00125-016-3873-z
Burhans, 2018, Contribution of Adipose Tissue Inflammation to the Development of Type 2 Diabetes Mellitus, Compr. Physiol., 9, 1
Agil, 2013, Melatonin ameliorates low-grade inflammation and oxidative stress in young Zucker diabetic fatty rats, J. Pineal Res., 54, 381, 10.1111/jpi.12012
Ozkanlar, 2016, Melatonin Modulates the Immune System Response and Inflammation in Diabetic Rats Experimentally-Induced by Alloxan, Horm. Metab. Res., 48, 137
Bazyar, 2019, The effects of melatonin supplementation in adjunct with non-surgical periodontal therapy on periodontal status, serum melatonin and inflammatory markers in type 2 diabetes mellitus patients with chronic periodontitis: A double-blind, placebo-controlled trial, Inflammopharmacology, 27, 67, 10.1007/s10787-018-0539-0
Jiang, 2016, Protective Effects of Melatonin on Retinal Inflammation and Oxidative Stress in Experimental Diabetic Retinopathy, Oxidative Med. Cell. Longev., 2016, 3528274, 10.1155/2016/3528274
Li, 2005, Melatonin reduces inflammatory injury through inhibiting NF-kappaB activation in rats with colitis, Mediat. Inflamm., 2005, 185, 10.1155/MI.2005.185
Sasaki, M., Jordan, P., Joh, T., Itoh, M., Jenkins, M., Pavlick, K., Minagar, A., and Alexander, S.J. (2002). Melatonin reduces TNF-a induced expression of MAdCAM-1 via inhibition of NF-kappaB. BMC Gastroenterol., 2.
Chuang, 1996, Effect of melatonin on NF-kappa-B DNA-binding activity in the rat spleen, Cell Biol. Int., 20, 687, 10.1006/cbir.1996.0091
Nayki, 2016, The effect of melatonin on oxidative stress and apoptosis in experimental diabetes mellitus-related ovarian injury, Gynecol. Endocrinol., 32, 421, 10.3109/09513590.2015.1126819
Negi, 2011, Melatonin modulates neuroinflammation and oxidative stress in experimental diabetic neuropathy: Effects on NF-kappaB and Nrf2 cascades, J. Pineal. Res., 50, 124, 10.1111/j.1600-079X.2010.00821.x
Zibolka, 2018, Distribution and density of melatonin receptors in human main pancreatic islet cell types, J. Pineal Res., 65, e12480, 10.1111/jpi.12480
Ramracheya, 2008, Function and expression of melatonin receptors on human pancreatic islets, J. Pineal Res., 44, 273, 10.1111/j.1600-079X.2007.00523.x
Muhlbauer, 2011, Melatonin inhibits insulin secretion in rat insulinoma beta-cells (INS-1) heterologously expressing the human melatonin receptor isoform MT2, J. Pineal Res., 51, 361, 10.1111/j.1600-079X.2011.00898.x
Poppema, 1987, Monoclonal antibodies (MT1, MT2, MB1, MB2, MB3) reactive with leukocyte subsets in paraffin-embedded tissue sections, Am. J. Pathol., 127, 418
Dubocovich, 2005, Functional MT1 and MT2 melatonin receptors in mammals, Endocrine, 27, 101, 10.1385/ENDO:27:2:101
Glebezdina, 2019, Molecular Mechanisms of Control of Differentiation of Regulatory T-Lymphocytes by Exogenous Melatonin, Dokl. Biochem. Biophys., 484, 13, 10.1134/S1607672919010058
Drazen, 2001, Melatonin receptor subtype MT2 (Mel 1b) and not mt1 (Mel 1a) is associated with melatonin-induced enhancement of cell-mediated and humoral immunity, Neuroendocrinology, 74, 178, 10.1159/000054684
Haldar, 1992, Effect of the pineal gland on circadian rhythmicity of colony forming units for granulocytes and macrophages (CFU-GM) from rat bone marrow cell cultures, J. Pineal Res., 12, 79, 10.1111/j.1600-079X.1992.tb00030.x
Libri, 1989, Pinealectomy inhibits interleukin-2 production and natural killer activity in mice, Int. J. Immunopharmacol., 11, 567, 10.1016/0192-0561(89)90187-2
Liu, 2013, Melatonin mediates protective effects on inflammatory response induced by interleukin-1 beta in human mesenchymal stem cells, J. Pineal Res., 55, 14, 10.1111/jpi.12045
Cevik, 2005, Exposure to continuous darkness ameliorates gastric and colonic inflammation in the rat: Both receptor and non-receptor-mediated processes, J. Gastroenterol. Hepatol., 20, 294, 10.1111/j.1440-1746.2004.03579.x
Karamitri, 2018, Type 2 diabetes-associated variants of the MT2 melatonin receptor affect distinct modes of signaling, Sci. Signal., 11, eaan6622, 10.1126/scisignal.aan6622
Lo, C.C., Lin, S.H., Chang, J.S., and Chien, Y.W. (2017). Effects of Melatonin on Glucose Homeostasis, Antioxidant Ability, and Adipokine Secretion in ICR Mice with NA/STZ-Induced Hyperglycemia. Nutrients, 9.
Dandekar, 2015, Cross talk between ER stress, oxidative stress, and inflammation in health and disease, Methods Mol. Biol., 1292, 205, 10.1007/978-1-4939-2522-3_15
Hill, 2013, Age-related decline in melatonin and its MT1 receptor are associated with decreased sensitivity to melatonin and enhanced mammary tumor growth, Curr. Aging Sci., 6, 125, 10.2174/1874609811306010016
Waldhauser, 1988, Alterations in nocturnal serum melatonin levels in humans with growth and aging, J. Clin. Endocrinol. Metab., 66, 648, 10.1210/jcem-66-3-648