Assessment of redox state and biochemical parameters of salivary glands in streptozotocin-induced diabetic male rats treated with mate tea (Ilex paraguariensis)

Diabetes Mellitus is a chronic metabolic disorder associated with persistent hyperglycemia, that affects approximately 463 million people around the world and is one of the main global health problems (Saeedi et al., 2019). This disease results from changes in insulin secretion and / or its action (American Diabetes Association Professional Practice Committee, 2022), leading to disturbances in metabolism of carbohydrates, proteins, and lipids. When not properly diagnosed and controlled, diabetes mellitus reduces life expectancy, as it can result in complications such as atherosclerosis, blindness, renal failure, amputation of extremities, and stroke. Hyperglycemia-induced oxidative stress has been identified as the main cause of complications from this metabolic disorder (Iacobini et al., 2021, Kocher et al., 2018, Martin-Gallan et al., 2003, Mustafa et al., 2021, Newsholme et al., 2016).

Regarding oral health, the severity of periodontal disease is more pronounced in diabetic patients, and these individuals also present greater risks of developing caries (Ferizi et al., 2018, Genco and Borgnakke, 2020, Verhulst et al., 2019). This prevalence is associated with changes in salivary flow rate, pH, and buffering capacity, alterations in the mineral composition and salivary proteins, and immune impairment of salivary function (Lima-Aragao et al., 2016, Mrag et al., 2020). These modifications occur, at least in part, due to salivary gland dysfunctions (Aitken-Saavedra et al., 2015, Hu et al., 1992, Mata et al., 2004).

Previous studies with a streptozotocin-induced diabetic animal experimental model associated hyperglycemia-induced disturbance of the redox status with alterations in the biochemical parameters of the salivary glands. In diabetic rats, increased superoxide dismutase (SOD), catalase (CAT), and lipid peroxidation were associated with higher deposition of collagen fibers in the parotid glands (Deconte et al., 2011). In turn, in the submandibular glands of diabetic rats, a reduction in amylase expression occurs concomitantly with an increase in lipid peroxidation (Bhattarai et al., 2018) and lower levels of total antioxidant capacity (Kang et al., 2021). Similarly, the disturbance in the redox state associated with reduced total protein content in the submandibular gland of diabetic rats was characterized by an increase in lipid peroxidation, protein oxidation, and SOD, in addition to a reduction in the reduced glutathione (GSH) concentration and glutathione peroxidase (GPx) activity (Peralta et al., 2019). In another study, increased lipid peroxidation and reduced SOD and GSH were accompanied by higher levels of autophagy markers microtubule-associated protein 1 light chain 3 (LC3), sequestosome 1/p62 (P62), and beclin-1 in the submandibular gland of diabetic rats (Asseri et al., 2022).

Around the world, medicinal plants are used to control and treat complications from diabetes mellitus (Hamza et al., 2010, Hsu et al., 2009, Taghipour et al., 2019). Evidence has shown the efficacy of the infusion of Ilex paraguariensis, called mate tea, as an adjunctive strategy for the treatment of diabetes mellitus complications (Kang et al., 2012) and to improve glycemic control and the lipid profile (Kang et al., 2012, Klein et al., 2011, Rocha et al., 2018), interfering with glucose absorption (Oliveira et al., 2008), or normalizing insulin signaling (Conceicao et al., 2017). Mate tea is a traditional low-cost drink widely consumed in Uruguay, Argentina, Paraguay, and southern Brazil, that contains a range of different bioactive substances, such as polyphenols, mainly chlorogenic acid derivatives, minerals, vitamins, amino acids, and some flavonoids (quercetin, luteolin, and rutin) (Gawron-Gzella et al., 2021, Heck and de Mejia, 2007). In Brazil, mate tea is an important source of phenolic compounds that contribute to the antioxidant capacity of the diet (Torres & Farah, 2017). In fact, mate tea has been shown to be efficient in alleviating pathologies and dysfunctions associated with redox state disorders resulting from diabetes mellitus (de Oliveira et al., 2018), aging (Pereira et al., 2017, Pereira et al., 2017), and testosterone deficiency (Cypriano et al., 2021).

Studies on the beneficial effects of natural extracts on the function and redox status of the salivary glands in the experimental model of streptozotocin-induced diabetes are restricted to research with extracts of Ixeris dentate (Bhattarai et al., 2018), Larrea divaricata Cav. (Peralta et al., 2019), and chamomile tea (Perestrelo et al., 2022). Taking into account the growing importance of alternative and complementary medicine, the antioxidant therapeutic properties of mate tea and the relationship of diabetes-induced oxidative stress on the biochemical parameters of the salivary glands, the purpose of the current work was to assess the effects of mate tea on the redox state and biochemical parameters of the salivary glands of streptozotocin-induced diabetic rats.

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