Lead-induced phospholipidosis and cholesterogenesis in rat tissues.
In order to investigate the effects of lead exposure on lipid metabolism, rats were exposed to 200, 300 and 400 ppm lead in their drinking water for 12 weeks. The lead exposure resulted in induction of phospholipidosis in kidney and brain of the animals. While renal phospholipidosis was accompanied with depletion of renal cholesterol, phospholipidosis in the brain was accompanied with enhanced cholesterogenesis and hypertriglyceridemia. Lead exposure also resulted in enhanced hepatic cholesterogenesis and this was accompanied with a decrease in triglyceride and phospholipid contents. While lead exposure did not affect erythrocyte phospholipids, there was a 37% increase in erythrocyte cholesterol in animals exposed to the 200 ppm lead dose. In the plasma, lead exposure resulted in a dose-dependent increase in free fatty acid concentration. Although phospholipids also decreased in the plasma as a result of lead exposure, the decrease was not dose-dependent. Lead exposure did not affect plasma and HDL cholesterol and triglyceride. A double fold increase in cholesterol/phospholipid ratio was observed in the brain of lead-exposed animals, whereas this ratio decreased in the kidney. Positive associations were observed between tissue cholesterol and phospholipids versus lead accumulation in blood, liver and kidney. In contrast however, negative associations were observed between tissue triglyceride and lead accumulation in liver and kidney. Our results suggest that induction of cholesterogenesis and phospholipidosis in tissues may be responsible for the subtle and insidious cellular effects of lead and that these cellular events may mediate the hepatotoxic, nephrotoxic and neurotoxic manifestations in lead intoxication.
Ademuyiwa
Oladipo
O
Toxicokinetics Section, Indian Institute of Toxicology Research [Council of Scientific and Industrial Research, India], Post Box 80, Mahatma Gandhi Marg, Lucknow 226001, Uttar Pradesh, India. adelad2@yahoo.com
Agarwal
Rakhi
R
Chandra
Ramesh
R
Behari
Jai Raj
JR
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002784:Cholesterol / Q000096:biosynthesis* / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D007854:Lead / Q000633:toxicity*; D008064:Lipidoses / Q000139:chemically induced* / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D010743:Phospholipids / Q000097:blood / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D010743:Phospholipids; D007854:Lead; D002784:Cholesterol