Gene expression and alterations of antioxidant enzymes in spleen of rats exposed to fluoride

Abstract

BackgroundFluorosis is a slow and progressive process causing metabolic, functional and structural damages affecting many tissues particularly musculoskeletal, dental systems, kidney, liver and brain. It can be rapidly absorbed by passive diffusion through the stomach, small intestine, mouth and skin. Endemic fluorosis is connected to the high concentration of fluoride in drinking water. The present study aimed to evaluate the toxic effects of sodium fluoride (NaF) on splenic activity at the biochemical and molecular level. Materials and methodsWistar albino rats were randomly assigned to three groups. The control rats were given 1 ml deionized water orally for 40 days. Groups II and III were administered 300 and 600 mg NaF/kg b.w. /day for the same period. Animals were sacrificed under ether anaesthesia. The spleen tissue was excised and used for biochemical and real-time PCR analysis. The level of fluoride, malondialdehyde (MDA), reduced glutathione (GSH) and activities of different antioxidant enzymes such as cytosolic copper/zinc superoxide dismutase (Cu/Zn SOD), glutathione peroxidase (GPx) and catalase (CAT) were determined. The analysis of gene expression of Cu/Zn SOD, GPx and CAT in spleen was done using Real-time PCR. ResultsThe levels of fluoride and MDA were significantly (P < 0.0001) increased where as GSH content decreased significantly (P < 0.0001) in the spleen of fluoridated rats. The activities of antioxidant enzymes viz; Cu/Zn SOD, GPx and CAT declined significantly (P < 0.0001) compared to the control. Pearson’s bivariate correlation and simple linear regression analysis exhibited strong positive correlation between levels of splenic tissue fluoride and MDA(r = 0.985) while negative correlations existed in GSH (r = −0.907) as well as activities of Cu/Zn SOD (r = −0.982), GPx (r = −0.966), and CAT (r = −0.935). The gene expression of Cu/Zn SOD, GPx and CAT were significantly (P < 0.0001) reduced in fluorotic rats. ConclusionIt is concluded that fluoride intoxication leads to the development of oxidative stress and damaging the cellular metabolism resulting in the declined ability of free radical scavengers along with increased level of MDA and decreased expression level of antioxidant genes which helps to understand the possible mechanism of fluoride-induced toxicity at the molecular level.