Role of NF-κB transcriptional factor activation during chronic fluoride intoxication in development of oxidative-nitrosative stress in rat’s gastric mucosa

Abstract

Fluoride compounds are known as hazardous environmental pollutants that can enter the body with drinking water. Chronic exposure to fluoride leads to development of oxidative stress and can lead to activation of nuclear factor κB (NF-κB). The aim of this work is to clarify the role of NF-kB activation in production of reactive nitrogen and oxygen species, activity of antioxidant enzymes and intensity of lipid peroxidation (LPO) in gastric mucosa of rats during chronic fluoride intoxication. Materials and methodsWe carried out the study on 18 mature male rats of the Wistar line. The animals were divided into 3 groups: control animals (6), group of chronic fluoride intoxication (6), and animals (6), which received the NF-κB inhibitor, namely ammonium pyrrolidine dithiocarbamate (PDTC) in a dose of 76 mg / kg (iNF-κB group) during modeling of chronic fluoride intoxication. To assess the development of oxidative stress we studied superoxide production (O2-), activity of superoxide dismutase (SOD), catalase (CAT) and concentration of free malondialdehyde (MDA). We also assessed NO production and concentration of its metabolites (peroxynitrite, nitrosilated thiol groups, nitrites). ResultsChronic fluoride intoxication leads to NO hyperproduction with subsequent increase in concentration of its later metabolites (peroxynitrite, nitrosilated thiol groups, nitrites). Production of O2- increases, SOD activity decreases, CAT activity increases and MDA concentration also increases. Inhibition of NF-kB activation by PDTC normalizes the parameters studied. ConclusionsActivation of NF-κB during chronic fluoride intoxication leads to the development of hyperproduction of NO and development of oxidative-nitrosative stress.