Abstract
Background
Lead has been shown to induce dyslipidemia in rats although the attendant mechanisms have not been clearly elucidated.
Methods
In order to investigate the time-course of lead-induced perturbations in lipid metabolism, male Wistar rats were exposed to 200, 300 and 400 ppm lead as lead acetate in their drinking water for 4, 8 and 12 weeks. Control animals received distilled water for the same exposure times after which blood, liver, kidney, brain, heart and lungs were removed from the animals and analyzed for lipid dynamics spectrophotometrically.
Results
Lead accumulated in the organs in the following descending order: kidney > liver > brain > heart > lungs. Lead-induced inhibition of reverse cholesterol transport was both time-dependent as well as dose-dependent at 4 and 8 weeks as evidenced by decrease in HDL cholesterol (17% in 4-week 400 ppm, 35, 43 and 49% in 200, 300 and 400 ppm doses respectively at 8 weeks). Free fatty acids (FFAs) in plasma displayed a hormetic-like response at 4 weeks with the lowest lead dose instigating a 51% decrease in FFA while 300 and 400 ppm doses displayed 2-fold and 1.5-fold increases respectively. Increases in plasma FFA were dose-dependent at 12 weeks. Increases in erythrocyte FFA were also observed in the 200 ppm dose at 4 weeks and in all the doses at 8 weeks. Increased hepatic, brain and renal cholesterogenesis were generally observed with highest increases occurring at 8 weeks in both organs. Hepatic, brain, renal, cardiac and pulmonary phospholipidosis were observed in all the lead doses and exposure times. Cardiac cholesterol decreased while triacyglycerols increased at 4 weeks. Hepatic and brain HMG-CoA reductase activities were generally up-regulated in most of the doses with highest increase (35%) occurring in 300 ppm lead dose at 4 weeks. Positive correlations were observed between liver lead and liver cholesterol (r = 0.476, p = 0.01), kidney lead and plasma FFA (r = 0.498, p = 0.01) while a negative correlation was observed between blood lead and HDL cholesterol (r = -0.523, p = 0.01).
Conclusion
These findings indicate that lead-induced dyslipidemia may be mediated through up-regulation of HMG-CoA reductase activity, inhibition of reverse cholesterol transport and enhanced phospholipidosis resulting from increased availability of FFA.