Immunohistochemical Study of Nrf2-Antioxidant Response Element as Indicator of Oxidative Stress Induced by Cadmium in Developing Rats.

Sergio Montes,Camilo Rios,Daniel Juárez-Rebollar,Yesica Heras-Romero,Marisela Méndez-Armenta,Concepción Nava-Ruíz,Aurora Sánchez-García

doi:10.1155/2015/570650

Abstract

In developing animals, Cadmium (Cd) induces toxicity to many organs including brain. Reactive oxygen species (ROS) are often implicated in Cd-inducedtoxicity and it has been clearly demonstrated that oxidative stress interferes with the expression of genes as well as transcriptional factors such as Nrf2-dependent Antioxidant Response Element (Nrf2-ARE). Cd-generated oxidative stress and elevated Nrf2 activity have been reported in vitro and in situ cells. In this study we evaluated the morphological changes and the expression pattern of Nrf2 and correlated them with the Cd concentrations in different ages of developing rats in heart, lung, kidney, liver, and brain. The Cd content in different organs of rats treated with the metal was increased in all ages assayed. Comparatively, lower Cd brain levels were found in rats intoxicated at the age of 12 days, then pups treated at 5, 10, or 15 days old, at the same metal dose. No evident changes, as a consequence of cadmium exposure, were evident in the morphological analysis in any of the ages assayed. However, Nrf2-ARE immunoreactivity was observed in 15-day-old rats exposed to Cd. Our results support that fully developed blood-brain barrier is an important protector against Cd entrance to brain and that Nrf2 increased expression is a part of protective mechanism against cadmium-induced toxicity.

Highlights

Cadmium, a heavy metal, is present in increasingly hazardous concentrations in soils, sediments, air, and water [1, 2]
Reactive oxygen species (ROS) are predominantly implicated and it has been clearly demonstrated that oxidative stress interferes with the expression of genes as well as several transcriptional factors such as metal regulatory transcription factor 1 (MTF1), AP-1 upstream stimulator factor (USF), nuclear factor-B (NF-κB), and NF-E2-related factor (Nrf2)
We look for morphological damage in brain from Cd-intoxicated pups and the expression of a transcriptional factor associated with oxidative stress defensive response

Summary

Introduction

A heavy metal, is present in increasingly hazardous concentrations in soils, sediments, air, and water [1, 2]. Acute exposure to Cd house dust, smoking, and/or occupational exposure produces pulmonary edema and hemorrhage, followed by inflammation, scarring, pulmonary edema, and respiratory tract irritation; whereas chronic exposure to Cd often leads to renal dysfunction, the kidney is still regarded as critical organ for its accumulation and toxicity. The liver is the major target organ of toxicity following acute Cd poisoning, Cd-induced inflammation being an important mechanism for Cd-induced oxidative stress. The mechanisms of cadmium toxicity are poorly understood, one of the major mechanisms behind heavy metal toxicity has been attributed to oxidative stress [7,8,9,10]

Methods

Results

Conclusion