Combined thirty-day exposure to thioacetamide and choline-deprivation alters serum antioxidant status and crucial brain enzyme activities in adult rats.
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).
Liapi
Charis
C
Department of Pharmacology, Medical School, National & Kapodistrian University of Athens, Athens, Greece.
Al-Humadi
Hussam
H
Zarros
Apostolos
A
Galanopoulou
Panagiota
P
Stolakis
Vasileios
V
Gkrouzman
Elena
E
Mellios
Zois
Z
Skandali
Nikolina
N
Anifantaki
Foteini
F
Tsakiris
Stylianos
S
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*
D000975:Antioxidants; D002273:Carcinogens; D013853:Thioacetamide; D000110:Acetylcholinesterase; D017301:Ca(2+) Mg(2+)-ATPase; D000254:Sodium-Potassium-Exchanging ATPase
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