Effects of chronic exposure to cadmium on prostate lipids and morphology

Abstract

Cadmium is an environmental toxic metal implicated in human prostate carcinogenesis. The mechanism of its toxicity is not fully understood. Previously, we showed that cadmium exposure induces oxidative stress, especially lipid peroxidation. This study evaluates the effect of chronic exposure to 0.886 mM of cadmium (Cd) per liter in the drinking water on prostate lipid content and metabolism in Wistar rats. We determined the lipid profile and measured the expression of lipogenic enzymes: FAS, GPAT, LPL, DGAT-1, DGAT-2, ACO, CPT-1 and CT, and of certain factors involved in lipid regulation and fatty acid transporters: FAT/CD36, E-FABP, SREBP-2, PPAR-gamma and PPAR-alpha by RT-PCR. Ultrastructure was analyzed by electron microscopy and, as prostate is an androgen controlled gland, AR expression was measured by RT-PCR and Western blot. Cd altered the prostatic lipid profile. Triglycerides (TG) and esterified cholesterol (EC) decreased, free cholesterol (FC) and phospholipids (PL) increased and total cholesterol (TC) did not change. FAS, MDH and IDH activities did not vary but G6PDH decreased significantly in Cd group. Regarding TG synthesis, DGAT-1 decreased while GPAT increased and FAS, LPL and DGAT-2 remained unchanged. Regarding beta oxidation, CPT-1 increased while ACO expression decreased in Cd group. In the PL pathway, CT expression was increased. All these results would justify the decrease of TG in Cd group when compared to control. In the cholesterol metabolic pathway, HMGCoAR and SREBP-2 increased. PPAR-alpha increased but PPAR-gamma did not change. Regarding fatty acid transporters, FAT/CD36 decreased, while E-FABP increased. AR mRNA and protein expression decreased. Ultrastructural analysis showed a decrease in lipid droplets and signs of cellular damage in the Cd group. Cadmium exposure induces important changes in prostatic lipid profile and metabolism, confirmed by the morphology analyses, which also showed signs of cellular damage. These results could be important to further understanding the complex mechanism of cadmium toxicity in prostate and in the development of better treatments for people and animals exposed to the heavy metal.

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“…Cd was found to dose-dependently down-regulate the plasma and erythrocyte concentrations of cholesterol, triacylglyceride and phospholipids the brain concentrations of cholesterol and triacylglyceride with a concomitant increase in phospholipids concentrations and decrease hepatic cell concentrations of cholesterol and phospholipids with a concomitant up-regulation in triacylglyceride concentrations significantly compared to control animals. These were in agreement with the findings of other researchers [23][24][25][26]. The data also indicate that the activity of MDA an end product of lipid peroxidation was up-regulated as a result of Cd-induction which is in consistent with previous researchers [24].…”

“…Several interpretations of these results could be considered. Firstly, the decrease in cholesterol may be due to inhibition of lecithin-cholesterol acyltransferase activity in Cd-treated rats [23,24]. Secondly, the cholesterol decreases in Cd-exposed animals suggests that Cd activates the acyl-CoA: cholesterol acyltransferase which catalyzes intracellular esterification of cholesterol and as such is involve in intestinal absorption of cholesterol hepatic assembly of ApoBcontaining lipoproteins foam cell formation and atherogenesis [27].…”

The Effect of Selenium and Lycopene on Oxidative Stress in Bone Tissue in Rats Exposed to Cadmium

“…It adversely affects many of the body's tissues, including bone [30]- [32]. The importance of nutritional supplements such as phytochemicals on lowering the harmful effects of Cd on the liver and kidney had been reported [29] [33].…”

Status of Prostate Specific Antigen and Alpha Fetoprotein in Nigerian E-Waste Workers: A Cancer Risk Predictive Study

“…PSA is normally present in blood at low level, the desirable level of PSA that is considered normal in men is less than 4ng/ml [12]. Previous reports have shown that PSA level is increased in heavy metal toxicity [13,14]. The significantly raised PSA concentration in the ewaste exposed group in this study may be linked to a trend towards metal-induced oxidative stress and the associate initiation of carcinogenesis caused by the effects of heavy metals on the prostate tissue.…”