N-acetylcysteine ameliorates carbofuran-induced alterations in lipid composition and activity of membrane bound enzymes.
The present work investigates the protective effects of N-acetylcysteine (NAC) on carbofuran-induced alterations in lipid composition and activity of membrane bound enzymes (Na+-K+-ATPase and Ca2+-ATPase) in the rat brain. Animals were exposed to carbofuran at a dose of 1 mg/kg body weight, orally, for a period of 28 days. A significant increase in lipid peroxidation in terms of TBARS was observed in brain after carbofuran exposure. NAC administration (200 mg/kg body weight) on the other hand lowered the carbofuran-induced lipid peroxidation to near normal. The increased lipid peroxidation following carbofuran exposure was accompanied by a significant decrease in the levels of total lipids, which is attributed to the reduction in phospholipid levels. Furthermore, NAC administration had a beneficial effect on carbofuran-induced alterations in lipid composition. The ratio of cholesterol to phospholipid, a major determinant of membrane fluidity, was increased in response to carbofuran exposure. This was associated with decreased activity of Na+-K+-ATPase and Ca2+-ATPase. NAC was observed to offer protection by restoring the cholesterol to phospholipid ratio along with the activity of Na+-K+-ATPase and Ca2+-ATPase. The results clearly suggest that carbofuran exerts its neurotoxic effects by increasing lipid peroxidation, altering lipid composition and activity of membrane bound enzymes. NAC administration ameliorated the effects of carbofuran suggesting its potential therapeutic effects in carbofuran neurotoxicity.
Department of Biochemistry, Panjab University, Basic Medical Science Building, BMS Block, Chandigarh 160014, India.
Amit
A
Kamboj
Ravi
R
Kiran
Rajat
R
Sandhir
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D000252:Calcium-Transporting ATPases / Q000378:metabolism*; D002235:Carbofuran / Q000633:toxicity*; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology; D007306:Insecticides / Q000633:toxicity; D050356:Lipid Metabolism / Q000187:drug effects*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D016166:Free Radical Scavengers; D007306:Insecticides; D010743:Phospholipids; D002784:Cholesterol; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase; D002235:Carbofuran; D000111:Acetylcysteine