ROS-mediated NRF2 Activity in Rats Exposed to Acrolein

Objectives Environmental exposure to acrolein has been linked to impaired vascular reactivity and development of cardiovascular diseases. Generation of free radicals and formation of adduct with critical proteins have been proposed as the possible mechanisms involved but the precise mechanism of acrolein mediated vascular alteration remains elusive. Peroxisome proliferator‐activated receptor gamma (PPARγ) has been implicated in the pathology of diseases involving inflammation. The nuclear factor erythroid 2‐related factor 2 (Nrf2) is an important regulator of adaptive response to oxidative stress. Nrf2 activity is regulated partially through Keap1 protein. Keap1 binding to Nrf2 will keep the transcription factor in the cytoplasm. This study hypothesizes that exposure of rats to acrolein alters activation of Nrf2 through modification of Keap1 and/or modification of Nrf2. Design and method Male Sprague‐Dawley rats (200–250 gm) were exposed to acrolein (1 mg/kg, gavage, 1 week) alone or in combination with rosiglitazone (Roz: PPARγ ligand; 10 mg/kg, gavages, 10 days). At the end of the treatment period, animals were sacrificed and isoprostane level was measured in urine as an indication of oxidative damage. ELISA and western blot analysis were used to measure changes in the expression/activity of Nrf2, Keap1 and HO‐1 in liver tissue. Results Our results indicated increased generation of ROS in rats treated with acrolein. Addition of rosiglitazone ameliorated the effect of acrolein on ROS generation. Acrolein increased expression/activity of Nrf2 and HO‐1, while reduced expression of Keap1. Addition of rosiglitazone further increased expression/activity of Nrf2 and HO‐1 and reduced Keap1. Conclusions Based on present data we are concluding that effect of acrolein on rat is partially due to the increased generation of ROS and subsequent alterations of Nrf2, Keap1 and HO‐1. These changes were further amplified with addition of rosiglitazone. Support or Funding Information National Institute Of General Medical Sciences of the National Institutes of Health, Award Number SC3GM103746. Research Center in Minority Institutions (RCMI), Molecular Biology Core facility of TSU. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .