Time Course of Lead-Induced Dyslipidemia in Male Wistar Rats
DOI:
https://doi.org/10.26538/tjdr/v2i9.5Keywords:
Lead, dyslipidemia, cholesterogenesis, free fatty acids, phospholipidosis, Hydoxymethylglutaryl coenzyme A reductase.Abstract
Purpose: Previous studies have linked lead toxicity to dyslipidemia. However, this has not been well characterized in a time course study. This study investigates the effects of lead exposure on lipid metabolism with time, using a rat model.
Method: Seventy-two (72) male Wistar rats were exposed to lead at concentrations of 0, 200, 300, and 400 ppm in their drinking water for 4, 8 and 12 weeks, after which blood, liver, kidney, brain, heart, spleen and lungs were removed from the animals and analyzed for lead and lipid dynamics.
Results: Lead-induced inhibition of reverse cholesterol transport was both time-dependent as well as dose-dependent at 4 and 8 weeks. Plasma free fatty acids (FFAs) displayed a hormetic-like response at 4 weeks and increased dose-dependently at 12 weeks while erythrocyte FFAs increased 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 exposures. Cardiac cholesterol decreased while triglycerides increased at 4 weeks. Increases in hepatic and brain cholesterogenesis were neither dose nor time-dependent. Correlation studies showed both direct and inverse correlations between tissue lead and various lipid parameters.
Conclusion: Lead exposure induced significant dyslipidemia and altered cholesterol metabolism over time, underscoring potential cardiovascular and metabolic risks.
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