LIPOPOLYSACCHARIDE-INDUCED SYSTEMIC INFLAMMATORY RESPONSE ENHANCES THE DEVELOPMENT OF OXIDATIVE-NITROSATIVE STRESS IN SALIVARY GLANDS OF RATS UNDER ALCOHOL DAMAGE
R.S. Kozaeva1, M.O. Klymenko1, V.О. Kostenko2
- Petro Mohyla Black Sea National University, Mykolayiv, Ukraine
- Poltava State Medical University, Ukraine
DOI: https://doi.org/10.15407/fz67.06.060
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.
Keywords:
lipopolysaccharide-induced systemic inflam- matory response; alcohol; oxidative-nitrosative stress; salivary glands.
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