title: Combined thirty-day exposure to thioacetamide and choline-deprivation alters serum antioxidant status and crucial brain enzyme activities in adult rats.
abstract: Choline (Ch) is an essential nutrient that seems to be involved in a wide variety of metabolic reactions and functions that affect the nervous system, while thioacetamide (TAA) is a well-known hepatotoxic agent. The induction of prolonged Ch-deprivation (CD) in rats receiving TAA (through the drinking water) provides an experimental model of mild progressive hepatotoxicity that could simulate commonly-presented cases in clinical practice. In this respect, the aim of this study was to investigate the effects of a 30-day dietary CD and/or TAA administration (300 mg/L of drinking water) on the serum total antioxidant status (TAS) and the activities of brain acetylcholinesterase (AChE), Na(+),K(+)-ATPase and Mg(2+)-ATPase of adult rats. Twenty male Wistar rats were divided into four groups: A (control), B (CD), C (TAA), D (CD+TAA). Dietary CD was provoked through the administration of Ch-deficient diet. Rats were sacrificed by decapitation at the end of the 30-day experimental period and whole brain enzymes were determined spectrophotometrically. Serum TAS was found significantly lowered by CD (-11% vs Control, p < 0.01) and CD+TAA administration (-19% vs Control, p < 0.001), but was not significantly altered due to TAA administration. The rat brain AChE activity was found significantly increased by TAA administration (+11% vs Control, p < 0.01), as well as by CD+TAA administration (+14% vs Control, p < 0.01). However, AChE was not found to be significantly altered by the 30-day dietary CD. On the other hand, CD caused a significant increase in brain Na(+),K(+)-ATPase activity (+16% vs Control, p < 0.05) and had no significant effect on Mg(2+)-ATPase. Exposure to TAA had no significant effect on Na(+),K(+)-ATPase, but inhibited Mg(2+)-ATPase (-20% vs Control, p < 0.05). When administered to CD rats, TAA caused a significant decrease in Na(+),K(+)-ATPase activity (-41% vs Control, p < 0.001), but Mg(2+)-ATPase activity was maintained into control levels. Our data revealed that an adult-onset 30-day dietary-induced CD had no effect on AChE activity. Treatment with TAA not only reversed the stimulatory effect of CD on adult rat brain Na(+),K(+)-ATPase, but caused a dramatic decrease in its activity (-41%). Previous studies have linked this inhibition with metabolic phenomena related to TAA-induced fulminant hepatic failure and encephalopathy. Our data suggest that CD (at least under the examined 30-day period) is an unfavorable background for the effect of TAA-induced hepatic damage on Na(+),K(+)-ATPase activity (an enzyme involved in neuronal excitability, metabolic energy production and neurotransmission).
authors.affiliation: Department of Pharmacology, Medical School, National & Kapodistrian University of Athens, Athens, Greece.
authors.forename: Charis
authors.initials: C
authors.lastname: Liapi
authors.forename: Hussam
authors.initials: H
authors.lastname: Al-Humadi
authors.forename: Apostolos
authors.initials: A
authors.lastname: Zarros
authors.forename: Panagiota
authors.initials: P
authors.lastname: Galanopoulou
authors.forename: Vasileios
authors.initials: V
authors.lastname: Stolakis
authors.forename: Elena
authors.initials: E
authors.lastname: Gkrouzman
authors.forename: Zois
authors.initials: Z
authors.lastname: Mellios
authors.forename: Nikolina
authors.initials: N
authors.lastname: Skandali
authors.forename: Foteini
authors.initials: F
authors.lastname: Anifantaki
authors.forename: Stylianos
authors.initials: S
authors.lastname: Tsakiris
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D001923:Brain Chemistry / Q000187:drug effects*; D017301:Ca(2+) Mg(2+)-ATPase / Q000378:metabolism; D002273:Carcinogens / Q000494:pharmacology*; D002796:Choline Deficiency / Q000378:metabolism*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013853:Thioacetamide / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D002273:Carcinogens; D013853:Thioacetamide; D000110:Acetylcholinesterase; D017301:Ca(2+) Mg(2+)-ATPase; D000254:Sodium-Potassium-Exchanging ATPase
references.citation: Neurosci Lett. 1990 Dec 11;120(2):159-62
references.pmid: 1705675
references.citation: J Lipid Res. 1968 Jul;9(4):437-46
references.pmid: 5725875
references.citation: J Neurochem. 1980 Jan;34(1):213-5
references.pmid: 7452237
references.citation: Jpn J Physiol. 1989;39(3):429-40
references.pmid: 2552204
references.citation: J Nutr. 2004 Oct;134(10):2504-8
references.pmid: 15465738
references.citation: Hepatol Res. 2004 Nov;30(3):141-147
references.pmid: 15588779
references.citation: Science. 1976 Feb 13;191(4227):561-2
references.pmid: 1251187
references.citation: Planta Med. 1993 Oct;59(5):418-20
references.pmid: 8255934
references.citation: FASEB J. 1998 Mar;12(3):349-57
references.pmid: 9506479
references.citation: Am J Clin Nutr. 2005 Oct;82(4):836-42
references.pmid: 16210714
references.citation: Teratology. 2001 Aug;64(2):114-22
references.pmid: 11460263
references.citation: J Biol Chem. 1951 Nov;193(1):265-75
references.pmid: 14907713
references.citation: Can J Physiol Pharmacol. 1977 Apr;55(2):170-9
references.pmid: 141320
references.citation: Metab Brain Dis. 2008 Sep;23(3):255-64
references.pmid: 18665440
references.citation: Vopr Med Khim. 1979 Jan-Feb;25(1):71-4
references.pmid: 218361
references.citation: Carcinogenesis. 2004 Apr;25(4):631-6
references.pmid: 14656942
references.citation: Z Naturforsch C J Biosci. 2000 Mar-Apr;55(3-4):271-7
references.pmid: 10817219
references.citation: Clin Chem Lab Med. 2007;45(5):651-6
references.pmid: 17484629
references.citation: Life Sci. 1968 Apr 1;7(7):419-28
references.pmid: 5652184
references.citation: Metab Brain Dis. 2008 Sep;23(3):289-301
references.pmid: 18642068
references.citation: Mech Ageing Dev. 2001 Apr 30;122(5):491-501
references.pmid: 11292514
references.citation: J Appl Toxicol. 2009 Mar;29(2):101-9
references.pmid: 18798224
references.citation: J Nutr. 2002 Apr;132(4):652-7
references.pmid: 11925456
references.citation: Nutrition. 2000 Jul-Aug;16(7-8):669-71
references.pmid: 10906592
references.citation: Biochem J. 1985 Dec 1;232(2):505-11
references.pmid: 4091805
references.citation: Hepatology. 1996 Aug;24(2):412-8
references.pmid: 8690413
references.citation: Naunyn Schmiedebergs Arch Pharmacol. 1981 Apr;316(2):131-4
references.pmid: 7242699
references.citation: Annu Rev Nutr. 1981;1:95-121
references.pmid: 6764726
references.citation: Nutr Rev. 1994 Oct;52(10):327-39
references.pmid: 7816350
references.citation: Exp Toxicol Pathol. 2005 Aug;57(1):65-75
references.pmid: 16089321
references.citation: Brain Res. 1987 Apr 7;408(1-2):399-402
references.pmid: 3036307
references.citation: J Pharmacol Exp Ther. 1984 Feb;228(2):304-11
references.pmid: 6141282
references.citation: Toxicology. 1988 Jan;48(1):81-5
references.pmid: 2892287
references.citation: Int J Dev Neurosci. 2002 Apr;20(2):77-81
references.pmid: 12034138
references.citation: Biochem Pharmacol. 1961 Jul;7:88-95
references.pmid: 13726518
references.citation: J Neurochem. 1974 Sep;23(3):611-3
references.pmid: 4279007
references.citation: Am J Clin Nutr. 2005 Oct;82(4):719-20
references.pmid: 16210698
references.citation: Exp Biol Med (Maywood). 2004 Nov;229(10):988-95
references.pmid: 15522834
references.citation: Hepatology. 1995 Nov;22(5):1399-403
references.pmid: 7590654