Chronic Fluoride Toxicity and Myocardial Damage: Antioxidant Offered Protection in Second Generation Rats
Keywords:Antioxidant supplementation, chronic fluorosis, oxidative stress, second generation
AbstractThis experiment was designed to investigate the extent of peroxidative changes and histological alterations in the myocardium of rats exposed to high fluoride for two generations, in addition to ameliorative role of selenium and vitamin E on the above indices. Adult albino Wistar rats were given fluoride through drinking water (200 ppm F) and maintained subsequently for two generations, while they were exposed to fluoride throughout the experiment. Fluoride treatment significantly increased the lipid peroxidation and decreased the activity of antioxidant enzymes, viz., catalase, superoxide dismutase, and glutathione level in auricle and ventricle regions of the heart. Decreased feed and water consumption, organ somatic index and marginal drop in body growth rate were observed. Decreased antioxidant enzymes and increased malondialdehyde levels might be related to oxidative damage that occurs variably in the myocardium of rats. Biochemical changes were supported by the histological observations, which also revealed that chronic exposure to fluoride causes damage to the myocardium. Results of this study can be taken as an index of cardio-toxicity in rats exposed to water fluoridation. Further, oral supplementation of selenium and vitamin E not only inhibited oxidative stress but also enhanced the activities of antioxidant enzymes. Administration of antioxidants during fluoride exposure significantly overcame cardiac fluoride toxicity and therefore may be a therapeutic strategy for fluorotic victims.
Cicek E, Aydin G, Akdogan M, Okutan H. Effects of chronic ingestion of sodium fluoride on myocardium in a second generation of rats. Hum Exp Toxicol 2005;24:79-87.
Waldbott GL, Burgstahler AW, McKinney HL, editors. Fluoridation: the great dilemma. Lawrence, Kansas: Coronado Press; 1978.
Okushi I. Changes of the heart muscle due to chronic fluorosis Part I. Electrocardiogram and cardiac X-rays in inhabitants of high fluoride zone. Shikoku Acta Med 1954;5:159-65.
Takamori T, editor. The heart changes of growing albino rats fed on varied contents of fluorine. The toxicology of fluorine symposium; 1962 Oct 15-17 Bern, Switzerland, Basel/Stuttgart: Schabe.
Pribilla O. Four cases of acute silicofluoride intoxication, Clinical and pathological findings. Fluoride 1968;1:102-9.
Chinoy NJ, editor. Studies on fluoride, aluminium and arsenic toxicity in mammals and amelioration by some antidotes In: Tripathi G, editor. Modern trends in environmental biology. New Delhi: 2002.
Niehaus WGJr, Samuelsson B. Formation of malonaldehyde from phospholipid arachidonate during microsomal lipid peroxidation. Eur J Biochem 1968;6:126-30.
Aebi H. Catalase in vitro. Met Enzymol 1984;105:121-6.
Misra HP, Fridovich I. The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase J Biol Chem 1972;247:3170-5.
Ellman GL. Tissue sulfhydrl groups. Arch Biochem Biophysics 1952;82:70-7.
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951;193:265-75.
Collins TF, Sprando RL, Black TN, Shackelford ME, Olejnik N, Ames MJ, et al. Developmental toxicity of sodium fluoride measured during multiple generations. Food Chem Toxicol 2001;39:867-76.
Verma RJ, Guna-Sherlin DM. Sodium fluoride-induced hypoproteinemia and hypoglycemia in parental and F(1)-generation rats and amelioration by vitamin. Food Chem Toxicol 2002;40:1781-8.
Leone NC, Geever EF, Moran NC. Acute and subacute toxicity studies of sodium fluoride in animals. Public Health Rep 1956;71:459-67.
Gutteridge JM, Halliwell B, editors. Antioxidants in nutrition, health and diseases. 1st ed. New York: Oxford University Press; 1994.
Halliwell B, Gutteridge JM. Free radicals, antioxidants, and human disease: where are we now. J Lab Clin Med 1992;119:598-620.
Zofia M, Mokrzynska AM, Juzyszyn Z. Effects of selenium on serum lipids and enzyme activities in fluorideintoxicated rats. Fluoride 2002;35:168-75.
Basha PM, Madhusudhan N. Pre and post natal exposure of fluoride induced oxidative macromolecular alterations in developing central nervous system of rat and amelioration by antioxidants. Neurochem Res 2010;35:1017-28.
El-Demerdash FM, Yousef MI, Kedwany FS, Baghdadi HH. Cadmium-induced changes in lipid peroxidation, blood hematology,biochemical parameters and semen quality of male rats protective role of vitamin E and B-carotene. Food Chem Toxicol 2004;42:1563-71.
Crewe HK, Nothey LM, Wunach RM. Metabolism of tamoxifen by recombinant human cytochrome p 450 enzymes formation of the 4- hydroxy and N-desmethyl metabolites and isomerization of trans-4- hydroxy-tamoxifen. Drug Metab Dispos 2002;30:869-74.
Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 2007;39:44-84.
Guney M, Oral B, Take G, Giray SG, Mungan T. Effect of fluoride intoxication on endometrial apoptosis and lipid peroxidation in rats: Role of vitamins E and C. Toxicology 2007;231:215-23.
Li G, Du X, Cheng X, Bi H. The effects in fluorosis of selenium on the biochemical elements in the blood of rats and the urinary fluoride of patients. Fifth conference of the Chinese society for fluoride research1 (Chinese) Kuenming1991.
Li YY, Sun GF, Li FJ, Liang G, Jia XP. Effect of Se and GSH on lipid peroxidation induced by fluoride: an experimental study. Proceedings of the PAN-Asia Pacific Conference on fluoride and arsenic research; Aug 16-20; Shenyang, China: 1999. p. 111.