Resveratrol acts as an antioxidant in leukocytes of patients with diabetes mellitus 2 through the AMPK signaling pathway
DOI:
https://doi.org/10.34119/bjhrv7n2-080Keywords:
Resveratrol, AMPK, diabetes mellitus 2Abstract
Diabetes is characterized by disturbances in serum glucose levels caused by insulin resistance, with consequent high blood glucose levels. Permanently increased blood glucose tends to lead to an increase in reactive oxygen species (ROS). Therefore, one of the mechanisms to contain this process is to consider antioxidant treatment. Within this context, resveratrol (RSV) stands out. Among the pathways of action of this compound, AMPK plays a fundamental role in regulating its antioxidant activity. The objective of the work aims to verify the antioxidant profile of RSV, through the AMPK pathway, in leukocytes of patients with type 2 diabetes mellitus (DM2) between 60 and 80 years old. 12 individuals were selected, divided into two groups: control group (n=6) and experimental group (n=6). After blood collection and leukocyte separation, the luminol-dependent chemiluminescence assay was performed. To analyze the involvement of the AMPK pathway, the inhibitor compound C was used. The result obtained showed that there was an antioxidant behavior of AMPK in cells stimulated with peroxide and treated with RSV, this in turn decreased the production of ROS in leukocytes of all samples, but this effect was less significant in DM2 patients. This oxidation, which is more pronounced in diabetics, can lead to target organ damage. As RSV played an important role in reducing ROS, we concluded that it is an important compound in preventing target organ damage in patients with this comorbidity, acting through the AMPK pathway.
References
Ahmad I., Hoda M. Molecular mechanisms of action of resveratrol in modulation of diabetic and non-diabetic cardiomyopathy. Pharmacol. Res., v.161, p.105112, 2020.
Baur J.A., Pearson K.J., Price N.L., Jamieson H.A., Lerin C., Kalra A., Prabhu V.V., Allard J.S., Lopez-Lluch G., Lewis K., et al. Resveratrol improves health and survival of mice on a high-calorie diet. Nature, v.444, p.337–342, 2006.
Burke A.P. et al. Morphologic findings of coronary atherosclerotic plaques in diabetics: a postmortem study. Arterioscler. Thromb. Vasc. Biol., v.24, p.1266–1271, 2004.
Caldeira C.A. et al. Resveratrol: Change of SIRT 1 and AMPK signaling pattern during the aging process. Experimental Gerontology, v.146, p.111226, 2021.
Canto C., Gerhart-Hines Z., Feige J.N., Lagouge M., Noriega L., Milne J.C., Elliott P.J., Puigserver P., Auwerx J. AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity. Nature, v. 458, p.1056–1060, 2009.
Cardoso ARG et al. Diabetes Mellitus: diagnóstico, avaliação e tratamento. Brazilian Journal of Health Review, v.7, n.1, p.7435–7446, 2024.
Do G.-M., Jung U.J., Park H.-J., Kwon E.-Y., Jeon S.-M., McGregor R.A., Choi M.-S. Resveratrol ameliorates diabetes-related metabolic changes via activation of AMP-activated protein kinase and its downstream targets in db/db mice. Mol. Nutr. Food Res., v.56, p.1282–1291, 2012.
Dos Santos VTH, Da Silva FH, Franco FN. Potencial terapêutico de antioxidantes no tratamento da hipertensão – uma revisão da literatura. Journal Archives of Health, v.4, n.4, p.1155-1170, 2023.
Ferreira-Fiochi RS, et al. Physical activity, grape juice, red wine and resveratrol effects in cardiac remodeling of Wistar rats submitted to a high fat diet. Brazilian Journal of Health Review, v.6, n.6, p.30358–30367, 2023.
Franco FN, de Cassia Cardoso L, Moura Silva BN, Rodrigues de Araújo G, Chaves MM. Aging: Change in SIRT1 and Enzymatic Profile Promotes a Decrease in the Antioxidant Capacity of Resveratrol in Human Leukocytes In Vitro. Curr Aging Sci., v.16, p.56-64, 2003.
Franco FN, de Cassia Cardoso L, Silva BNM, de Araújo GR, Chaves MM. Aging: silencing the PKA and AkT/PKB signaling pathways alters the antioxidant capacity of resveratrol. Biogerontology, v.24, p.913-923, 2023.
Giacco F, Brownlee M. Oxidative stress and diabetic complications. Circ Res., v.107, p.1058-70, 2010.
Guellich A., Damy T., LeCarpentier Y., Conti M., Claes V., Samuel J.-L., Quillard J., Hébert J.-L., Pineau T., Coirault C. Role of oxidative stress in cardiac dysfunction of PPARα−/− mice. Am. J. Physiol. Heart Circ. Physiol., v.293, p.93-102, 2007.
Hayashida S., Arimoto A., Kuramoto Y., Kozako T., Honda S.-I., Shimeno H., Soeda S. Fasting promotes the expression of SIRT1, an NAD+-dependent protein deacetylase, via activation of PPARα in mice. Mol. Cell. Biochem., v.339, p.285–292, 2010.
Hernandez-Mijares A. et al. Human leukocyte/endothelial cell interactions and mitochondrial dysfunction in type 2 diabetic patients and their association with silent myocardial ischemia. Diabetes Care, v.36, p.1695–1702, 2013.
Huang D., Shi G., Jiang Y., Yao C., Zhu C. A review on the potential of Resveratrol in prevention and therapy of diabetes and diabetic complications, Biomedicine & Pharmacotherapy, v.125, p.109767, 2020.
International Organization for Standardization. ISO 10993‐5: Biological Evaluation of Medical Devices. Part 5: Tests For In Vitro Cytotoxicity. Switzerland: ISO; 2009.
Joshi T. et al. Targeting AMPK signaling pathway by natural products for treatment of diabetes mellitus and its complications. J Cell Physiol, v.234, p.17212–17231, 2019.
Korshunov SS, Skulachev VP, Starkov AA. High protonic potential actuates a mechanism of production of reactive oxygen species in mitochondria. FEBS Lett., v.416, p.15–18, 1997.
Poblete-Aro C. et al. Efecto del ejercicio físico sobre marcadores de estrés oxidativo en pacientes con diabetes mellitus tipo 2 [Exercise and oxidative stress in type 2 diabetes mellitus]. Rev Med Chil., v.146, p.362-372, 2018.
Poynter M., Daynes R.A. Peroxisome proliferator-activated receptor α activation modulates cellular redox status, represses nuclear factor-κb signaling, and reduces inflammatory cytokine production in aging. J. Biol. Chem., v.273, p.32833–32841, 1998.
Rogers N.H., Witczak C.A., Hirshman M.F., Goodyear L.J., Greenberg A.S. Estradiol stimulates Akt, AMP-activated protein kinase (AMPK) and TBC1D1/4, but not glucose uptake in rat soleus. Biochem. Biophys. Res. Commun., v.382, p.646–650, 2009.
Ruderman N., Prentki M. AMP kinase and malonyl-CoA: Targets for therapy of the metabolic syndrome. Nat. Rev. Drug Discov, v.3, p.340–351, 2004.
Saltiel A.R. & Kahn C.R. Insulin signalling and the regulation of glucose and lipid metabolism. Nature, v.414, p.799–806, 2021.
Tan Z., Zhou L.-J., Mu P.-W., Liu S.-P., Chen S.-J., Fu X.-D., Wang T.-H. Caveolin-3 is involved in the protection of resveratrol against high-fat-diet-induced insulin resistance by promoting GLUT4 translocation to the plasma membrane in skeletal muscle of ovariectomized rats. J. Nutr. Biochem., v.23, p.1716–1724, 2012.
Yu T, Robotham JL, Yoon Y. Increased production of reactive oxygen species in hyperglycemic conditions requires dynamic change of mitochondrial morphology. Proc Natl Acad Sci U S A, v.103 p.2653–8., 2006.
Yu X.Y. et al. Hyperglycemic myocardial damage is mediated by proinflammatory cytokine: macrophage migration inhibitory factor. PLoS One, v.6, p.16239, 2011.


