Abstract
Still little is known about the role of oxidative stress (OS) in the pathogenesis of the salivary gland dysfunction in the course of insulin resistance (IR). To induce IR rats was fed with a high fat diet (HFD) during 8 weeks. Stimulated and non-stimulated salivary flow rate, total protein, as well as oxidative damage markers: 4-HNE protein adduct, 8-isoprostanes (8-isoP), 8-hydroxy-D-guanosine (8-OHdG), advanced oxidation protein product (AOPP), and protein carbonyls (PC) were determined in the plasma and submandibular and parotid glands of IR and control rats. We have shown a significant decrease (45%) of the stimulated salivary flow rate, and in the total protein concentration in the parotid (35%) and submandibular (10%) glands of HFD IR as compared to the control rats. The level of 4-HNE protein adduct (15%) and 8-isoP (20%) in the submandibular glands of IR rats as well as total level of 4-HNE protein adduct (39%), 8-isoP (27%), AOPP (25%), PC (32%), and 8-OHdG (18%) in the parotid glands of IR rats were significantly higher as compared to the control group. We showed no correlation between the assessed OS parameters in the plasma and salivary glands. However, the redox balance in both glands shifted toward the oxidative status, parotid glands of IR rats are exposed to greater intensity OS. Stimulated secretory ability and mechanisms involved in the synthesis/secretion of proteins in the salivary glands are depressed in the course of IR. Oxidative damage in the salivary glands arises independently from the general OS in the course of insulin resistance induced by a high fat diet.
Highlights
The fact that global population is becoming more obese due to the growing sedentary lifestyle and higher caloric intake results in an increase in insulin resistance (IR), which may be defined as reduced sensitivity to insulin in target tissues (Erejuwa, 2012)
Despite the fact that average daily food intake was similar in both groups, high fat diet (HFD)-IR rats presented with a higher body weight when compared to the control rats (p = 0.0002) (Table 1)
On the contrary to submandibular glands, parotid glands of HFD-IR rats showed the severity of oxidative modifications of all types of cellular elements, which we observed in the form of significant increases in concentrations of 4-HNE-protein adduct (39%), 8-isoP (27%), 8-OHdG (18%), advanced oxidation protein product (AOPP) (25%), and protein carbonyls (PC) (32%) when compared to the control group (p = 0.003, p = 0.03, p = 0.035, p = 0.023 p = 0.002, respectively)
Summary
The fact that global population is becoming more obese due to the growing sedentary lifestyle and higher caloric intake results in an increase in insulin resistance (IR), which may be defined as reduced sensitivity to insulin in target tissues (Erejuwa, 2012). Excess production of ROS damages all important cellular components, such as DNA, lipids, and proteins, as well as disrupts cellular metabolism including altered gene expression, signal transduction, cell growth, and apoptosis. The result of the amino acids oxidation may be a cleavage of the polypeptide chain, as well as formation of crosslinks within one or more polypeptide chains (Stadtman and Levine, 2003). All of these result in a loss of activity and function of oxidatively modified proteins, with all biological consequences for the cell. OS and its cytopathological consequences have been implicated in the onset and pathology of periodontitis (Pendyala et al, 2013; Öngöz Dede et al, 2016), oral precancer (Agha-Hosseini et al, 2012), and cancer (Bahar et al, 2007; AghaHosseini et al, 2012) as well as in the alteration of the salivary glands function in the course of general diseases (Su et al, 2010; Zalewska et al, 2014a, 2015; Knas et al, 2016a,b)
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