title: Ethanol and age enhances fluoride toxicity through oxidative stress and mitochondrial dysfunctions in rat intestine.
abstract: 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.
authors.forename: Shailender Singh
authors.initials: SS
authors.lastname: Chauhan
authors.forename: Akhtar
authors.initials: A
authors.lastname: Mahmood
authors.forename: Sudarshan
authors.initials: S
authors.lastname: Ojha
mesh_terms: D000367:Age Factors; D000375:Aging; D000818:Animals; D002374:Catalase / Q000378:metabolism; D002956:Citrulline / Q000378:metabolism; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012969:Sodium Fluoride / Q000378:metabolism* / Q000633:toxicity*; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D045222:Electron Transport Chain Complex Proteins; D013438:Sulfhydryl Compounds; D002956:Citrulline; D009569:Nitric Oxide; D000431:Ethanol; D012969:Sodium Fluoride; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D005982:Glutathione Transferase; D005978:Glutathione
references.citation: J Neurochem. 1997 Aug;69(2):581-93
references.pmid: 9231715
references.citation: Basic Clin Pharmacol Toxicol. 2005 Jun;96(6):475-9
references.pmid: 15910412
references.citation: Neurotoxicol Teratol. 1995 Nov-Dec;17(6):685-8
references.pmid: 8747751
references.citation: Indian J Clin Biochem. 2007 Mar;22(1):99-104
references.pmid: 23105661
references.citation: Rev Roum Physiol (1990). 1991 Jan-Jun;28(1-2):63-7
references.pmid: 1817670
references.citation: J Cell Biol. 1963 Nov;19:293-307
references.pmid: 14090748
references.citation: J Clin Gastroenterol. 1994 Apr;18(3):194-9
references.pmid: 8034913
references.citation: Arch Biochem Biophys. 1995 Apr 1;318(1):53-8
references.pmid: 7726572
references.citation: Exp Gerontol. 2003 May;38(5):507-17
references.pmid: 12742528
references.citation: Free Radic Biol Med. 1995 Jul;19(1):121-7
references.pmid: 7635354
references.citation: Arch Biochem Biophys. 1996 Apr 15;328(2):309-16
references.pmid: 8645009
references.citation: Am J Physiol Cell Physiol. 2007 Feb;292(2):C670-86
references.pmid: 17020935
references.citation: J Trace Elem Med Biol. 2006;20(2):83-7
references.pmid: 16785047
references.citation: Alcohol Alcohol. 1990;25(2-3):231-7
references.pmid: 2198038
references.citation: Genes Nutr. 2010 Jun;5(2):101-9
references.pmid: 20606811
references.citation: Chem Biol Interact. 2010 Nov 5;188(2):319-33
references.pmid: 20650267
references.citation: Mol Pharmacol. 1995 Nov;48(5):825-34
references.pmid: 7476912
references.citation: Mediators Inflamm. 2012;2012:102954
references.pmid: 22933830
references.citation: Anal Biochem. 1980 Sep 15;107(2):424-31
references.pmid: 7435971
references.citation: Mol Aspects Med. 2004 Feb-Apr;25(1-2):5-16
references.pmid: 15051312
references.citation: Curr Clin Pharmacol. 2007 May;2(2):145-53
references.pmid: 18690862
references.citation: Proc Natl Acad Sci U S A. 1998 Jun 23;95(13):7631-6
references.pmid: 9636201
references.citation: Methods Find Exp Clin Pharmacol. 2007 Mar;29(2):93-9
references.pmid: 17440625
references.citation: Gastroenterology. 2002 Jun;122(7):2049-63
references.pmid: 12055609
references.citation: Am J Clin Nutr. 1985 Aug;42(2):289-95
references.pmid: 4025199
references.citation: Metabolism. 1998 Oct;47(10):1269-73
references.pmid: 9781633
references.citation: Environ Toxicol Pharmacol. 2003 Apr;13(3):199-204
references.pmid: 21782655
references.citation: Cell Immunol. 1993 Jun;149(1):50-64
references.pmid: 7685661
references.citation: Curr Opin Neurobiol. 1996 Oct;6(5):661-6
references.pmid: 8937831
references.citation: Alcohol. 2011 Nov;45(7):663-72
references.pmid: 21145694
references.citation: Int J Dev Neurosci. 2008 Apr;26(2):217-23
references.pmid: 18207349
references.citation: Adv Exp Med Biol. 1976;74:182-227
references.pmid: 183467
references.citation: Alcohol Alcohol. 1994 Jul;29(4):375-83
references.pmid: 7986274