Synergistic effect of chronic-cadmium exposure and soybean-based diet on oxidative stress-inflammation and apotosis in the hippocampus of rats

Abstract

Cadmium (Cd) is an environmental and industrial pollutant foundin water resources. Experimental and population studies haveshown that chronic exposure to Cd causes severe toxic effects invarious organs including in the brain, but information on hippocampus(Hp) is limited. Soybean is an important source of protein andisoflavones. Herein we hypothesized that a chronic exposure to lowconcentrations of Cd in the drinking water can cause oxidative/inflammationchanges and apoptosis in the hippocampus (Hp); andwhether a soybean-based diet (SBD) may modulate these effects.To accomplish this goal, we fed 4 groups of female Wistar-rats for60 days as follows: casein-based diet + tap water (CBD); CBD + tapwater with 15 ppm Cd (CBD+Cd); soybean-based diet + tap water(SBD); and SBD + tap water with 15 ppm Cd (SBD+Cd). After exposure,markers of oxidative stress/inflammation and apoptosis weremeasured in Hp. Compared to the Hp of CBD fed rats, the Hp ofCBD-Cd showed a reduced cyclooxigenase-2 expression, but didnot change Nrf2 expression and apoptotic profile (high p53 and highBax/Bcl2 ratio). However, a SBD caused a pro-apoptosis pattern,i.e, increased p53 and Bax expression, reduced Bcl-2 expressionand increased Bax/Bcl2 ratio. Although we did not observe Nrf2expression in the Hp of SBD fed rats, Nrf2 signaling pathway andgenes under ARE control may be induced. Indeed, we observe anantioxidant response in the Hp, which may account for the inductionof antioxidant enzyme expression (CAT, SOD and GPX). Regardlessincreased antioxidant enzymes, Cd exposure in SBD fed ratshad a synergistic effect in lipid peroxidation and protein oxidationin the Hp. Taking together our data suggest that a SBD and Cd-exposurehave a synergistic effect on oxidative stress/inflammationand apoptosis in Hp. Caution may be taken on using soybean as asource of protein in patients chronically exposed to Cd.