LIPOPOLYSACCHARIDE-INDUCED SYSTEMIC INFLAMMATORY RESPONSE ENHANCES THE DEVELOPMENT OF OXIDATIVE-NITROSATIVE STRESS IN SALIVARY GLANDS OF RATS UNDER ALCOHOL DAMAGE

Abstract

We addressed the role of lipopolysaccharide (LPS)-induced systemic inflammatory response (SIR) in the development of oxidative-nitrosative stress in the salivary glands of rats under the influence of alcohol. Ethanol (40%) at the dose of 24 mg/kg was administered intraperitoneally (ip) twice per day for 14 days. SIR was induced by ip administration of LPS (Salmonella typhi) at the dose 0.4 mg/kg for 1 week followed by a weekly LPS administration for 7 weeks. We found that long-term administration of ethanol in the back- ground of LPS-induced SIR increased the circulating level of proinflammatory markers (TNFa, IL-6) and C-reactive protein and this increase exceeded the respective values when LPS and alcohol were administered separately. Under these conditions, in submandibular salivary glands, the superoxide anion production by mitochondria respiratory chain was increased by 25.9 and 30.5%, by microsomal monooxygenases and NO synthase by 19.0 and 27,1%, by phagocyte NADPH-oxidase by 29.5 and 30.0%. The activity of inducible NO-synthase increased by 15.5 and 83.6%, the concentration of peroxynitrites of alkali and alkali-earth metals elevated by 32.5 and 58, 3%, and S- nitrosothiols raised by 20.2 and 22.7%. These changes were accompanied by a decrease in α-amylase activity and the aquaporin-5 concentration that impairs water and protein excretion by salivary glands. We conclude that adminis- tration of ethanol in the background of LPS-induced SIR results in more pronounced development of oxidative- nitrosative stress in the submandibular salivary glands and more marked dysfunction compared to separate use of LPS and alcohol.