Introduction: Fluoride toxicity causes irreversible damage to soft tissues like brain, liver, heart and lung.Fluoridetoxicity and hypoxiaexposure might alterhepatic oxygen sensing cell signaling mechanisms and asupplementation of antioxidant like l-ascorbic acid might have protective role.Aim: To investigate the exposure of sodium fluoride or hypoxia alone or in combination with or withoutadministration of L- ascorbic acid on biochemical and transcriptional pathways in hepato toxicity .Materials and Method: Male albino rats were divided into 8 groups (n= 6/group), group I(control), groupII (l-ascorbic acid, 50 mg/100g. b.wt), group III (hypoxia, 10% O2), group IV (NaF;20 mg/kg b.wt/day; ip),group V (NaF + hypoxia, 10% O2), group VI (l–ascorbic acid + hypoxia, 10% O2), group VII (l-ascorbicacid + NaF) and group VIII (l-ascorbic acid + NaF + hypoxia, 10% O2). The treatments were carried for 21days. Gravimetry, serumoxidant and antioxidant status were assessed by using spectrophotometer, serumlevels of vascular endothelial growth factor (VEGF ) and nitric oxide synthase 3(NOS3) was done by ELISAtechnique. Histopathological evaluations of hepatic tissue were done. ANOVA followed by “Tukey” testwere done for analysis of data in between the groups.Results: Gravimetry and biochemical evaluation showed significant decrease in body weight hepatosomaticindex, altered serum SOD, MDA, vitamin C, vitamin E, nitric oxide and hepatic vitamin Cin rats treatedwith hypoxia (group III), NaF (group IV) and NaF with hypoxia (group V). In case of l-ascorbic acidsupplementation in group VI, VII and VIII showed remarkable improvement. Alteration in serum VEGF,NOS3 andhistopathology of liver in rats treated with hypoxia, NaFand hypoxia with NaFindicate hepaticdysfunction by oxidative and nitrosative stress, whereas l-ascorbic acid supplementation were found to bebeneficial against fluoride and hypoxia induced alteration of hepatic function. Conclusion: Supplementation of L-ascorbicacid is salubrious to combat both sodiumfluoride and hypoxia induced oxidative &Nitrosative stress.
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