Early life permethrin treatment leads to long-term cardiotoxicity

Abstract

Environmental, nutritional or hormonal influences in early life may have long-term effects changing homeostatic processes and physiological parameters in adulthood. NF-kB and Nrf2, two of the main transcription factors regulating genes involved in pro-inflammatory and antioxidant responses respectively, can be modified by various stimuli. NF-kB controls immediate early genes and is required for cardiomyocyte hypertrophic growth, while Nrf2 protects the heart from oxidative stress-induced cardiovascular complications. The aim of this study was to investigate the impact of early life permethrin treatment (1/50 of LD50, from 6th to 21st day of life) on the development of cardiotoxicity in 500-day-old rats. Nrf2 and NF-kB gene expression, calcium level and heart surface area were chosen as biomarkers of toxicity. Six candidate reference genes were first examined and GAPDH resulted the most stable one for RT-qPCR. The comparative expression analysis of the target genes showed 1.62-fold increase in Nrf2 mRNA level, while the NF-kB mRNA in treated rats was not significantly changed compared to control ones. A significant decrease in heart surface area was observed in treated rats (296.59 ± 8.09, mm(2)) with respect to the control group (320.86 ± 4.93, mm(2)). Finally, the intracellular calcium influx in heart of early life treated rats increased 4.33-fold compared to the control one. In conclusion, early life pesticide exposure to low doses of permethrin insecticide, has long-term consequences leading to cardiac hypotrophy, increased calcium and Nrf2 gene expression levels in old age.

Keywords: Calcium; Cardiac hypotrophy; Early-life; Nrf2; Old age; Permethrin.