Environmental arsenic exposure and its contribution to human diseases, toxicity mechanism and management.

Arsenic is a well-recognized environmental contaminant that occurs naturally through geogenic processes in the aquifer. More than 200 million people around the world are potentially exposed to the elevated level of arsenic mostly from Asia and Latin America. Many adverse health effects including skin diseases (i.e., arsenicosis, hyperkeratosis, pigmentation changes), carcinogenesis, and neurological diseases have been reported due to arsenic exposure. In addition, arsenic has recently been shown to contribute to the onset of non-communicable diseases, such as diabetes mellitus and cardiovascular diseases. The mechanisms involved in arsenic-induced diabetes are pancreatic ß-cell dysfunction and death, impaired insulin secretion, insulin resistance and reduced cellular glucose transport. Whereas, the most proposed mechanisms of arsenic-induced hypertension are oxidative stress, disruption of nitric oxide signaling, altered vascular response to neurotransmitters and impaired vascular muscle calcium (Ca2+) signaling, damage of renal, and interference with the renin-angiotensin system (RAS). However, the contributions of arsenic exposure to non-communicable diseases are complex and multifaceted, and little information is available about the molecular mechanisms involved in arsenic-induced non-communicable diseases and also no suitable therapeutic target identified yet. Therefore, in the future, more basic research is necessary to identify the appropriate therapeutic target for the treatment and management of arsenic-induced non-communicable diseases. Several reports demonstrated that a daily balanced diet with proper nutrient supplements (vitamins, micronutrients, natural antioxidants) has shown effective to reduce the damages caused by arsenic exposure. Arsenic detoxication through natural compounds or nutraceuticals is considered a cost-effective treatment/management and researchers should focus on these alternative options. This review paper explores the scenarios of arsenic contamination in groundwater with an emphasis on public health concerns. It also demonstrated arsenic sources, biogeochemistry, toxicity mechanisms with therapeutic targets, arsenic exposure-related human diseases, and onsets of cardiovascular diseases as well as feasible management options for arsenic toxicity.

Rats with metabolic syndrome resist the protective effects of N-acetyl l-cystein against impaired spermatogenesis induced by high-phosphorus/zinc-free diet.

Consumption of relatively high amounts of processed food can result in abnormal nutritional status, such as zinc deficiency or phosphorus excess. Moreover, hyperphosphatemia and hypozincemia are found in some patients with diabetic nephropathy and metabolic syndrome. The present study investigated the effects of high-phosphorus/zinc-free diet on the reproductive function of spontaneously hypertensive rats/NDmcr-cp (SHR/cp), a model of the metabolic syndrome. We also investigated the effects of antioxidant, N-acetyl-l-cysteine (NAC), on testicular dysfunction under such conditions. Male SHR/cp and control rats (Wistar Kyoto rats, WKY) were divided into three groups; rats fed control diet (P 0.3%, w/w; Zn 0.2%, w/w), high-phosphorus and zinc-deficient diet (P 1.2%, w/w; Zn 0.0%, w/w) with vehicle, or high-phosphorus and zinc-deficient diet with NAC (1.5mg/g/day) for 12 weeks (n=6 or 8 rats/group). The weights of testis and epididymis were significantly reduced by high-phosphate/zinc-free diet in both SHR/cp and WKY. The same diet significantly reduced caudal epididymal sperm count and motility and induced histopathological changes in the testis in both strains. Treatment with NAC provided significant protection against the toxic effects of the diet on testicular function in WKY, but not in SHR/cp. The lack of the protective effects of NAC on impaired spermatogenesis in SHR/cp could be due to the more pronounced state of oxidative stress observed in these rats compared with WKY.

[Change of gonad gene expression profile in male F344 rats after exposure to 1-bromopropane].

OBJECTIVE: To study the 1-bromopropane (1-BP)-induced altered gene expression profiles in rat gonad, and explore its male reproductive toxicity-related mRNA changes. METHODS: Twelve F344/NSIc male rats were randomly divided into two groups of 6 each. Rats were exposed to either fresh air or 5030 mg/m3 1-BP through inhalation for 8 h. Rats were sacrificed and testes were removed at 16 h after exposure. Global changes in gene expression were determined by microarray analysis using rat genital chip followed by Real-time PCR validation. RESULTS: Among the 5082 genes and ESTs in the genital chip, 62 genes were down-regulated and 3 genes were up-regulated by 1-BP, which include synthetic sex hormone-related genes cytochrome P450 aromatase (CYP19a), glutathione S-transferase (GSTT1), creatine kinase (Ckb), myelin and lymphocyte protein (Mal) and S100 calcium-binding protein (S100a4). Classification analysis revealed that the majority of gene changes was involved protein/lipid metabolism, followed by the stress-associated defense response. Real-time PCR confirmed the down-regulation of CYP19a, GSTT1, Mal and S100a4 genes. CONCLUSION: Acute high-dose exposure to 1-BP causes the down-regulation of testicular CYP19a, S100a4, GSTT1 and Mal. This altered gene profiles might reflect the toxic mechanism which suggested that 1-BP disrupt the metabolics and endocrine balance.

Chemopreventive effect of selenium-enriched Japanese radish sprout against breast cancer induced by 7,12-dimethylbenz[a]anthracene in rats.

Breast cancer is one of the major cancers in women, and dietary intake must be controlled to prevent it. Selenium (Se), especially Se compound in vegetables, is thought to be a promising chemopreventive dietary ingredient for preventing breast cancer. In this study, we developed Se-enriched Japanese radish sprout using a special Se-additional fertilizer, and identified the Se chemical forms. The newly developed Se-enriched sprout is produced within a week by the tank forming method, and the major chemical form was identified as Se-methylselenocysteine (MeSeCys) (80%). Then, the chemopreventive effects of the Se-enriched sprout were investigated using Sprague-Dawley female rats with mammary cancer, induced by a single oral dose of 10 mg or 14 mg of 7, 12-dimethylbenz[a]anthracene (DMBA). Mammary tumors were found in 11, 16 and 2 rats treated with DMBA and thereafter fed the basal (n = 34), sprout-added basal (n = 30) and Se-enriched sprout-added test diets (n = 30), respectively. The incidence of mammary tumors was significantly lower in the Se-enriched sprout-added test diet group (7%) than in the basal diet group (32%) or sprout-added basal diet group (53%). In contrast, no significant difference was detected in the numbers and incidence of the tumor between the basal diet group and Se-enriched sprout-added test diet group before DMBA-dosing. These results suggest that the diet supplement of Se-enriched sprout after DMBA-dosing provides a significant chemoprevention against chemical-induced mammary cancer. Thus, Se-enriched sprout may be a useful dietary ingredient for preventing breast cancer.