Rutin prevents cardiac oxidative stress and inflammation induced by bisphenol A and dibutyl phthalate exposure via NRF-2/NF-κB pathway

Aim Environmental pollutants such as plastic-component substances (phthalates and bisphenol A) that coexist in natural ecosystems have been linked to an increase in the occurrence of human health hazards, particularly cardiovascular health. This study was designed to investigate single and combined cardio-toxic effects of dibutyl phthalate and bisphenol-A and the possible interventional role of rutin. Materials and methods Forty-two rats were randomized into 7 groups of 6 animals each and were treated as follows for 28 days: Control (0.1% DMSO), Bisphenol-A (BPA, 25 mg/kg, p.o), Dibutyl phthalate (DBP, 25 mg/kg, p.o), BPA + Rutin (25 mg/kg, Rt 50 mg/kg), DBP + Rt (25 mg/kg, Rt 50 mg/kg), BPA + DBP, BPA + DBP + Rt. Cardiac lipid peroxidation, antioxidants and inflammatory markers activities were measured. Key findings The result showed that BPA reduced the superoxide dismutase (SOD) activity, DBP and DBP+ BPA reduced the catalase (CAT) activity, DBP reduced glutathione (GSH) and nuclear factor erythroid 2-related factor 2 (Nrf2) while malondialdehyde (MDA) increased in DBP + BPA group. Also, DBP increased tissue C-reactive protein (CRP); DBP, DBP + BPA increased tissue nuclear factor kappa B (NF-κB); DBP + BPA increased plasma CRP; BPA increased plasma NF-κB. However, rutin efficiently reduced MDA level, CRP and NF-κB; increasing SOD, GSH and Nrf2 levels in DBP and BPA exposed rats. Significance These results revealed that bisphenol and dibutyl phthalate exposure caused oxidative stress and inflammation in the heart through Nrf2/NF-κB signaling pathway while oral administration of rutin prevents these effects via upregulation of Nrf2 and suppression of NF-κB signaling pathway.