Acetaminophen at Different Doses Protects Brain Microsomal Ca2+-ATPase and the Antioxidant Redox System in Rats

被引:32
作者
Naziroglu, Mustafa [1 ]
Cihangir Uguz, A. [1 ]
Kocak, Ahmet [2 ]
Bal, Ramazan [3 ]
机构
[1] Suleyman Demirel Univ, Dept Biophys, Fac TIP Med, TR-32260 Isparta, Turkey
[2] Suleyman Demirel Univ, Dept Histol & Embryol, Fac Med, TR-32260 Isparta, Turkey
[3] Firat Univ, Dept Biophys, Fac Med, TR-23169 Elazig, Turkey
关键词
Acetaminophen; Antioxidant; Oxidative stress; Brain; Apoptosis; Ca2+-ATPase; Rat; INDUCED OXIDATIVE STRESS; LIVER; ACTIVATION; NEURONS; PEROXYNITRITE; MITOCHONDRIA; GENERATION; DEFICIENT; CHANNELS; SELENIUM;
D O I
10.1007/s00232-009-9203-3
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Acetaminophen, an analgesic and antipyretic drug, rescues neuronal cells from mitochondrial redox impairment and reactive oxygen species (ROS). Excessive administration of acetaminophen above the recommended daily dose range has some negative effects on the brain. We investigated the effects of different doses of acetaminophen on Ca2+-ATPase and the antioxidant redox system in rats. Seventy rats were randomly divided into seven equal groups. The first was used for the control. One dose of 5, 10, 20, 100, 200, and 500 mg/kg acetaminophen was intraperitoneally administered to rats constituting the second, third, fourth, fifth, sixth, and seventh groups, respectively. After 24 h, brain cortical samples were taken and brain microsomal samples were obtained by ultracentrifugation. Brain and microsomal lipid peroxidation (LP) and brain calcium levels in the sixth and seventh groups were increased compared to control. LP levels in the second, third, and forth groups; brain vitamin E levels; brain and microsomal glutathione peroxidase (GSH-Px); and Ca2+-ATPase activity in the sixth and seventh groups were lower than in control, although brain vitamin E concentrations in the second, third, fourth, and fifth groups and microsomal GSH-Px activity in the third and fourth groups were higher than in control. Brain cortical beta-carotene and vitamin A concentrations did not differ in the seven groups. In conclusion, 5-100 mg/kg acetaminophen seems to have protective effects on oxidative stress-induced brain toxicity by inhibiting free radicals and supporting the antioxidant redox system.
引用
收藏
页码:57 / 64
页数:8
相关论文
共 40 条
[1]   Acetaminophen protects hippocampal neurons and PC12 cultures from amyloid β-peptides induced oxidative stress and reduces NF-κB activation [J].
Bisaglia, M ;
Venezia, V ;
Piccioli, P ;
Stanzione, S ;
Porcile, C ;
Russo, C ;
Mancini, F ;
Milanese, C ;
Schettini, G .
NEUROCHEMISTRY INTERNATIONAL, 2002, 41 (01) :43-54
[2]   Dissection of mitochondrial Ca2+ uptake and release fluxes in situ after depolarization-evoked [Ca2+]i elevations in sympathetic neurons [J].
Colegrove, SL ;
Albrecht, MA ;
Friel, DD .
JOURNAL OF GENERAL PHYSIOLOGY, 2000, 115 (03) :351-369
[3]  
DESAI ID, 1984, METHOD ENZYMOL, V105, P138, DOI 10.1016/S0076-6879(84)05019-9
[4]   Mitochondria and calcium: from cell signalling to cell death [J].
Duchen, MR .
JOURNAL OF PHYSIOLOGY-LONDON, 2000, 529 (01) :57-68
[5]   Protective effects of lamotrigine, aripiprazole and escitalopram on depression-induced oxidative stress in rat brain [J].
Eren, Ibrahim ;
Naziroglu, Mustafa ;
Demirdas, Arif .
NEUROCHEMICAL RESEARCH, 2007, 32 (07) :1188-1195
[6]   Ethanol stimulates ROS generation by mitochondria through Ca2+ mobilization and increases GFAP content in rat hippocampal astrocytes [J].
Gonzalez, Antonio ;
Pariente, Jose A. ;
Salido, Gines M. .
BRAIN RESEARCH, 2007, 1178 :28-37
[7]   Alteration of cytosolic free calcium homeostasis by SIN-1:: high sensitivity of L-type Ca2+ channels to extracellular oxidative/nitrosative stress in cerebellar granule cells [J].
Gutiérrez-Martín, Y ;
Martín-Romero, FJ ;
Henao, F ;
Gutiérrez-Merino, C .
JOURNAL OF NEUROCHEMISTRY, 2005, 92 (04) :973-989
[8]   Acetaminophen-mediated cardioprotection via inhibition of the mitochondrial permeability transition pore-induced apoptotic pathway [J].
Hadzimichalis, Norell M. ;
Baliga, Sunanda S. ;
Golfetti, Roseli ;
Jaques, Kathryn M. ;
Firestein, Bonnie L. ;
Merrill, Gary F. .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2007, 293 (06) :H3348-H3355
[9]   Oxidative stress and neurodegeneration: where are we now? [J].
Halliwell, Barry .
JOURNAL OF NEUROCHEMISTRY, 2006, 97 (06) :1634-1658
[10]   Acetaminophen-induced hepatotoxicity [J].
James, LP ;
Mayeux, PR ;
Hinson, JA .
DRUG METABOLISM AND DISPOSITION, 2003, 31 (12) :1499-1506