Early life permethrin treatment leads to long-term cardiotoxicity

•Early life pesticide exposure has long-term consequences on heart.•A significant decrease in heart surface area was observed in treated rats.•Calcium and Nrf2 gene expression levels were increased in old age.

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, mm2) with respect to the control group (320.86 ± 4.93, mm2). 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.