Ethanol and Age Enhances Fluoride Toxicity through Oxidative Stress and Mitochondrial Dysfunctions in Rat Intestine

Department of Gastroenterology, Post Graduate Institute of Medical Education and Research (PGIMER), Sector-12, Chandigarh, 160012, India, .
Molecular and Cellular Biochemistry (Impact Factor: 2.39). 09/2013; 384(1-2). DOI: 10.1007/s11010-013-1804-6
Source: PubMed


Fluoride toxicity and alcohol abuse are the two serious public health problems in many parts of the world. The current study was an attempt to investigate the effect of alcohol administration and age on fluoride toxicity in rat intestine. Six and 18 months old female Sprague Dawley rats were exposed to sodium fluoride (NaF, 25 mg/kg), 30 % ethanol (EtOH, 1 ml/kg), and NaF+EtOH (25 mg/kg+1 ml/kg) for a period of 20, 40, and 90 days. The levels of lipid peroxidation were increased, while the content of reduced glutathione, total, and protein thiol was decreased with NaF treatment. Under these conditions, animals showed an age-related decline in the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione-S-transferase which were further aggravated upon NaF or/and EtOH treatment. Mitochondrial respiration rate and the activities of complexes I, II, and IV enzymes of electron transport chain were decreased, while the levels of nitric oxide and citrulline were increased with age and NaF or/and EtOH treatment. Histological examination revealed large reactive lymphoid follicles, excess of lymphocytes in lamina propria of villi, villous edema, focal ileitis, necrosis of villi, and ulceration in NaF- or/and EtOH-treated animals in both the age groups. These findings suggest that fluoride mediate its toxic effects on intestine through oxidative stress and mitochondrial dysfunctions which are further augmented with alcohol consumption and advancing age.

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    ABSTRACT: The current investigation was designed to study the effect of chronic fluoride (F) ingestion and aging on disaccharidase activities and intestinal solute uptake in ethanol fed rats. Sodium fluoride (NaF, 25mg/kg) or/and 30 % ethanol (EtOH, 1ml/kg) was given to 6 and 18 month- old animals daily through intra-gastric route for 20, 40, and 90 days. Disaccharidase activities in intestinal brush border membrane (BBM) were significantly decreased with age and NaF or/and EtOH treatments. However, in each age group, the observed decline in enzyme activities was maximum in co-treated animals. Intestinal solute uptake in control group showed a significant decline with age. Animals receiving F exhibited a progressive increase (6 month) and decline (18 month) in solute uptake from day 20 to 90. Administration of EtOH alone or together with F showed a significant reduction in intestinal solute uptake in both age groups. These findings suggest that F and aging impairs disaccharidase enzyme activities and the intestinal solute uptake in duration specific manner which are aggravated with alcohol co-administration. These changes may affect the overall absorptive and transport functions in the gastrointestinal tract.
    Full-text · Article · Jan 2015 · Fluoride