Late-life Cardiac Injury in Rats following Early Life Exposure to Lead: Reversal Effect of Nutrient Metal Mixture

Cardiovascular Toxicology(2019)

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Abstract
Early-life exposure to lead (Pb) can lead to health effects in later life. The neurotoxic effects of Pb have been well documented but its effects on the heart are poorly elucidated. We examined the late life cardiac impairments resulting from developmental exposure to Pb. Further, we investigated the protective effect of the nutrient metal mixture containing calcium (Ca), zinc (Zn) and iron (Fe) against Pb-induced long-term effects on cardiac functions.Male albino rats were lactationally exposed to 0.2% Pb-acetate or 0.2% Pb-acetate together nutrient metal mixture as 0.02% in drinking water of the mother from PND 1 to PND 21. The results showed increased levels of serum total cholesterol (TC), triglycerides (TG), low-density lipoproteins (LDLs) and lactate dehydrogenase (LDH) activity at postnatal day (PND) 28 [young], 4 months [adult] and 18 months [old] age group rats. Most notably, exposure to Pb decreased the activities of mitochondrial superoxide dismutase (SOD), thioredoxin reductase (TrxR), aconitase (Acon), isocitrate dehydrogenase (ICDH), xanthine oxidase (XO) and total antioxidant status while the MDA levels increased in all selected age groups of rats. The histological findings showed an age-dependent response to Pb exposure evidenced by extensive degeneration and necrosis in cardiac muscle, disruption in muscle connectivity, hemorrhage, and mononuclear cell infiltration. Co-administration of nutrient metal mixture reversed the Pb-induced cardiac impairments as reflected in the recovery of the chosen sensitive markers of oxidative stress, reduced Pb levels and cardiac tissue changes. In conclusion, the data demonstrate that early-life exposure to Pb continuously influence the cardiac mitochondrial functions from early life to older age and further suggesting that adequate intake of nutrient metals may be potential therapeutic treatment for Pb intoxication.
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Key words
Lead exposure, Long-term effect, Essential nutrient metals, Oxidative stress, Mitochondria, Aging rats
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