Abstract
Complications generated by hyperglycemia present in diabetes mellitus (DM) have been constantly related to oxidative stress and dysfunction in the mitochondrial electron transport chain (ETC). Sirtuin 3 (SIRT3), which is present in mitochondria, is responsible for regulating several proteins involved in metabolic homeostasis and oxidative stress. Studies have suggested alterations in the expression of SIRT3 in DM. The objective of this study was to evaluate the effects of phenolic compounds in jabuticaba (Plinia trunciflora), a berry native to Brazil, on the activity of mitochondrial ETC complexes, SIRT3 protein expression, and oxidative stress parameters in liver of diabetic rats induced by streptozotocin. After type 1 DM induction (streptozotocin 65 mg/kg), diabetic and healthy rats were treated with jabuticaba peel extract (JPE) by gavage (0.5 g/kg of weight) for 30 days. After treatments, those diabetic rats presented impaired activities of complexes I, II, and III of ETC along with an overexpression of SIRT3. In addition, an increase in lipid peroxidation and superoxide dismutase and catalase activities was observed in the diabetic group. The treatment with JPE was able to recover the activity of the mitochondrial complexes and reduce the expression of SIRT3. Furthermore, JPE treatment reduced oxidative damage to lipids and brought the antioxidants enzyme activities to basal levels in diabetic rats. Together, these results demonstrate that JPE can reduce oxidative stress related to DM by restoring mitochondrial complexes activity and regulating SIRT3 expression. Thus, JPE could become an alternative to reduce the development of complications related to DM.
Highlights
Diabetes mellitus (DM) is a metabolic disease characterized primarily by hyperglycemia, as a result of the absolute absence of insulin, resistance to the action of insulin, or both
The group of diabetic rats that was treated with jabuticaba peel extract (JPE) maintained high blood glucose levels demonstrating that the extract had no effect on this parameter
The two-way ANOVA analysis demonstrated a statistically significant interaction between the effect of treatment with JPE and the presence or absence of DM in CI, CII, and complex III (CIII) activity (p = 0.0001, p = 0.031, p = 0.0001, respectively). This means that JPE modulates CI, CII, and CIII activity only when DM is present
Summary
Diabetes mellitus (DM) is a metabolic disease characterized primarily by hyperglycemia, as a result of the absolute absence of insulin, resistance to the action of insulin, or both. Type 1 DM (DM1) is characterized by an absolute insulin deficiency, usually due to an autoimmune destruction of pancreatic beta cells (American Diabete Association, 2014). This type constitutes about 5–10% of all cases of DM. Studies have shown the involvement of oxidative stress and dysfunction of the activity of mitochondrial complexes in complications related to DM1, such as cardiomyopathy and liver disease (Regnell and Lernmark, 2011; Al-Hussaini et al, 2012; Mohamed et al, 2016; Rukavina-Mikusic et al, 2021)
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