Immunohistochemical Study of Cell Proliferation, Bcl-2, p53, and Caspase-3 Expression on Preneoplastic Changes Induced by Cadmium and Zinc Chloride in the Ventral Rat Prostate

Abstract

This work was directed to evaluate immunoexpression of markers for apoptosis, resistance to apoptosis, and cell proliferation, as well as estimates of nuclear size in ventral prostate of rats treated with cadmium chloride and cadmium+zinc chloride because a possible protective effect of zinc has been postulated. The following variables were studied: volume fraction (VF) of Bcl-2 immunostaining, percentage of cells immunoreactive to proliferating cell nuclear antigen (LIPCNA) and p53 (LIp53), numerical density of caspase-3 immunoreactive cells (NV caspase-3), and estimates of volume-weighted mean nuclear volume (upsilonV). The LIPCNA and VF of Bcl-2 were significantly increased in the treated animals. The dysplasias (independent of their origin) showed a significant increase of the LIp53, NV caspase-3, and upsilonV in comparison with normal acini from treated and control animals. It can be concluded that cell proliferation is enhanced in long-term cadmium-exposed rats, and exposure to zinc combined with cadmium had no effect on any of the variables studied when comparing with normal acini. The increase of nuclear upsilonV could indicate a more aggressive behavior for pretumoral lesions.

Chemopreventive effects of zinc on prostate carcinogenesis induced by N-methyl-N-nitrosourea and testosterone in adult male Sprague-Dawley rats

“…Previous studies have shown that the caspase-3 expression, a key executioner of apoptotic machinery, was decreased in prostate cancer (Arriazu et al 2006). This study also demonstrates a signiWcant decrease in caspase-3 protein level in MNU + T treatment.…”

“…The p53-induced apoptosis can be blocked by gene-transfer-mediated elevations in the levels of the bcl-2 protein, suggesting that p53 and bcl-2 may participate in a common pathway for regulation of cell life and death (Arriazu et al 2006). The attenuating eVect of Bcl-X L and increased level of p53 proteins by zinc may be due to the conformational change in the protein structure and increases its aYnity for speciWc sequences of p53 as it tightly bound to zinc ions (Arriazu et al 2006), thereby stimulating the transcriptional activity of cell-cycle regulators (p21, GADD45, etc.) involved in the cell-cycle progression (Fanzo et al 2001).…”

“…Zinc supplementation begun a week before the administration of initial dose of testosterone propionate administration and throughout the studies. The dose was selected based on the previous studies by Arriazu et al (2006). Group IV: rats received zinc chloride (100 ppm/kg body weight) alone.…”

Rutin ameliorates cyclophosphamide induced oxidative stress and inflammation in Wistar rats: Role of NFκB/MAPK pathway

“…Percentages of NFjB immunostained nuclei were calculated in each selected section for control rats, toxicant treated rats and rats given rutin as a modulator using the following formula: number of labeled nuclei  100/total number (labeled + unlabeled) of nuclei [39]. NFjB immunostained nuclei were considered positive regardless of staining intensity.…”

Impact Assessment of Cadmium Toxicity and Its Bioavailability in Human Cell Lines (Caco-2 and HL-7702)

“…It is generally assumed that, after inhalation or ingestion of typical inorganic Cd compounds and after transferring across the alveolar membranes or intestinal wall, the major fraction of Cd initially accumulates in the liver [10]. In vitro and in vivo studies have depicted that low Cd concentrations (<5.0  μ M) might enhance cell proliferation in a dose-dependent manner [11, 12], while its higher concentrations (>5.0  μ M) could induce apoptosis in many tissues and organs [13]. …”