Cadmium Impairs p53 Activity in HepG2 Cells

Cadmium and cadmium compounds are contaminants of the environment, food, and drinking water and are important constituents of cigarette smoke. Cd exposure has also been associated with airborne particulate CdO and with Cd-containing quantum dots in medical therapy. Adverse cadmium effects reported in the literature have stimulated during recent years an ongoing discussion to better elucidate cadmium outcomes at cell and molecular level. The present work is designed to gain an insight into the mechanism of p53 impairment at gene and protein level to understand Cd-induced resistance to apoptosis. We used a hepatoma cell line (HepG2) derived from liver, known to be metal responsive. At genotoxic cadmium concentrations no cell cycle arrest was observed. The p53 at gene and protein level was not regulated. Fluorescence images showed that p53 was correctly translocated into the nucleus but that the p21Cip1/WAF-1, a downstream protein of p53 network involved in cell cycle regulation, was not activated at the highest cadmium concentrations used. The miRNAs analysis revealed an upregulation of mir-372, an miRNA able to affect p21Cip1/WAF-1 expression and promote cell cycle progression and proliferation. The role of metallothioneins and possible conformational changes of p53 are discussed.

Reduced Life Expectancy Model for Effects of Long Term Exposure on Lethal Toxicity with Fish

A model based on the concept of reduction in life expectancy (RLE model) as a result of long term exposure to toxicant has been developed which has normal life expectancy (NLT) as a fixed limiting point for a species. The model is based on the equation (LC50 = a ln(LT50) + b) where a and b are constants. It was evaluated by plotting ln LT50 against LC50 with data on organic toxicants obtained from the scientific literature. Linear relationships between LC50 and ln LT50 were obtained and a Calculated NLT was derived from the plots. The Calculated NLT obtained was in good agreement with the Reported NLT obtained from the literature. Estimation of toxicity at any exposure time and concentration is possible using the model. The use of NLT as a reference point is important since it provides a data point independent of the toxicity data set and limits the data to the range where toxicity occurs. This novel approach, which represents a departure from Haber's rule, can be used to estimate long term toxicity from limited available acute toxicity data for fish exposed to organic biocides.

Paraben Levels in an Urban Community of Western Canada

With effective antibacterial and antifungal properties, commercially used parabens are synthetic compounds widely utilized as preservatives in cosmetics, personal care products, pharmaceuticals, and as an additive in some foodstuffs. While long regarded as relatively safe and nontoxic, recent research has demonstrated xenoestrogenic properties of anthropogenic parabens with early evidence that paraben exposure may be linked to breast cancer, thyroid dysfunction, allergy, and obesity. In an attempt to determine the prevalence of paraben exposure in a Canadian urban community, a sample of convenience was done by measuring urinary levels of methyl, ethyl, propyl, butyl, and isobutyl parabens (MP, EP, PP, BP, and IP) in 39 consecutive patients in an Alberta primary care clinic. In 28 female patients including 9 pregnant women, the median urinary levels (in μg/L) were 25.45 for MP, 10.17 for EP, 2.80 for PP, 0.30 for BP, and 0.24 for IP. In 11 male patients, the median urinary levels (in μg/L) were 25.95 for MP, 10.37 for EP, 3.09 for PP, 0.35 for BP, and 0.22 for IP. Especially high urinary paraben levels were reported in a few patients, with the highest urinary concentrations (in μg/L) reported as 966.46 for MP, 220.6 as EP, and 612.73 for PP. It is evident that exposure to assorted parabens is a routine event for many if not most individuals, including pregnant women, in urban Alberta, Canada.

Cytotoxic Effects of Benzene Metabolites on Human Sperm Function: An In Vitro Study

In recent years, individuals are rampantly exposed to vapours of benzene, through paint, plastic, petroleum industries, fuel exhaust, and tobacco smoke. Hence the present investigation was directed towards determining the effect of benzene metabolites, namely, phenol-hydroquinone and catechol, on the motility, viability, and nuclear integrity of the human spermatozoa. From the results obtained it was clear that exposure to phenol-hydroquinone caused a significant decline in both, sperm motility and viability. Exposure to a phenol-hydroquinone (Phase I) microenvironment may therefore inhibit metabolically active enzymes, thus impeding ATP production, and in turn lowers sperm motility and viability. In addition, the present study also revealed that both metabolites of benzene caused significant denaturation of sperm nuclear DNA. Hence, exposure to phenol-hydroquinone in vitro could have resulted in generation of free radicals and altered membrane function, which is reflected by a decline in the motility, viability, and loss of sperm nuclear DNA integrity. In Phase II, the exposure of human sperm in vitro to varied concentrations of catechol caused only insignificant changes in sperm motility and viability as compared to those observed on exposure to phenol-hydroquinone. Hence, exposure to catechol appeared to have less toxic effects than those of phenol-hydroquinone.

Activation of the NFκB Pathway Enhances AhR Expression in Intestinal Caco-2 Cells

Recent data suggest that apart from its well-known role in the regulation of xenobiotic metabolizing enzymes, AhR is also involved in inflammation. However, the influence of inflammation on AhR expression remains unknown. Here, we demonstrated that proinflammatory conditions induced by either PMA or IL-1β enhance AhR expression in Caco-2 cells. This was associated with an increase in AhR promoter activity. By means of directed mutagenesis experiments and the use of proteasome inhibitors, we demonstrated that inflammation-induced AhR expression involved the NFκB pathway but not AP-1. Moreover, conditioned media from PMA-treated Caco-2 cells were also able to induce AhR expression, and this induction was repressed by anti-IL-1β blocking antibodies. Similar results were obtained with conditioned media from PMA-treated THP-1 cells. Taken together, these data suggest that AhR could be involved in vivo in an inflammatory loop. AhR was recently suspected to be implicated in inflammatory bowel disease. Our results support this hypothesis and suggest that AhR could be a new target for inflammatory bowel disease patient management.

Differential Bacteriostatic Effects of Sucralose on Various Species of Environmental Bacteria

Sucralose was developed as a low-cost artificial sweetener that is nonmetabolizable and can withstand changes in pH and temperature. It is not degraded by the wastewater treatment process and thus has been found in waste water, estuaries, rivers and the Gulf Stream. Since the molecule can withstand heat, acidification, and microbial degradation, it is accumulating in the environment. The highest concentration of environmental sucralose detected to date is 300 ng/L. Our lab has isolated six bacterial species from areas that have been exposed to sucralose. We then cultured these isolates in the presence of sucralose looking for potential sucralose metabolism or growth acceleration. Instead we found something very interesting, bacteriostatic effects exhibited on all six isolates. This inhibition was directly proportional to the concentration of sucralose exposure. The efficiency of the growth inhibition seemed to be species specific, with various concentrations inhibiting each organism differently.

Potential Toxic Levels of Cyanide in Almonds (Prunus amygdalus), Apricot Kernels (Prunus armeniaca), and Almond Syrup

Under normal environmental conditions, many plants synthesize cyanogenic glycosides, which are able to release hydrogen cyanide upon hydrolysis. Each year, there are frequent livestock and occasional human victims of cyanogenic plants consumption. The present work aims to determine the hydrocyanic acid content in different samples of cyanogenic plants, selected from the Tunisian flora, and in the almond syrup. In order to evaluate their toxicity and their impact on the consumer health in the short term as well as in the long term, using the ISO 2164-1975 NT standard, relating to the determination of cyanogenic heterosides in leguminous plants.

Inhibition of Nitric Oxide Synthase by L-NAME Promotes Cisplatin-Induced Nephrotoxicity in Male Rats

Objective. Nitric oxide (NO) has numerous important functions in the kidney. The role of NO in cisplatin (CP)-induced nephrotoxicity is not completely understood. This study was designed to determine the role of NO synthase inhibitor (L-NAME) on the severity of CP-induced nephrotoxicity in rats. Methods. Sixty four male (M) and female (F) Wistar rats were randomly divided into eight groups. The sham groups (group 1, male, n=6 and group 2, female, n=6) received saline. Groups 3 (male, n=8) and 4 (female, n=8) were treated with L-NAME (4 mg/kg, i.p.), and groups 5 (male, n=8) and 6 (female, n=8) received CP (3 mg/kg) for 7 days. Groups 7 (male, n=8) and 8 (female, n=8) were treated with L-NAME and CP for 7 days. Results. The CP-alone treated rats showed weight loss and increase in serum levels of blood urea nitrogen (BUN) and creatinine (Cr). Coadministration of L-NAME and CP did not improve weight loss, and it increased the levels of BUN and Cr in male but not in female rats (P<0.05). CP alone increased kidney damage significantly (P<0.05 ), however, the damage induced by combination of CP and L-NAME was gender-related. Conclusion. NOS inhibition by L-NAME increased CP-induced nephrotoxicity, which was gender-related.

Gastrointestinal Elimination of Perfluorinated Compounds Using Cholestyramine and Chlorella pyrenoidosa

Background. While perfluorinated compounds (PFCs) are a family of commonly used synthetic compounds with many applications, some PFCs remain persistent within the human body due, in part, to enterohepatic recirculation and renal tubular reabsorption. With increasing recognition of potential harm to human health associated with PFC bioaccumulation, interventions to facilitate elimination of these toxicants are welcome in order to potentially preclude or overcome illness. Minimal research has been undertaken thus far on methods to accelerate human clearance of PFCs. Methods. To test for possible oral treatments to hasten PFC elimination, a group of individuals with elevated PFC levels was treated with cholestyramine (CSM) and, after a break, was subsequently treated with Chlorella pyrenoidosa (CP). Stool samples were collected from all participants (i) prior to any treatment, (ii) during treatment with CSM, and (iii) during treatment with CP. Results. With CSM treatment, significant levels of three distinct PFCs were found in all stools, while levels were mostly undetectable prior to treatment. Following treatment with oral CP, undetectable or very low levels of all PFCs were noted in each sample tested. Conclusion. CSM appears to facilitate elimination of some common PFCs and may have some role in the clinical management of patients with accrued PFCs.

Biomonitoring and Elimination of Perfluorinated Compounds and Polychlorinated Biphenyls through Perspiration: Blood, Urine, and Sweat Study

Perfluorinated compounds (PFCs) are man-made organofluorine chemicals manufactured and marketed for their stain-resistant properties. Polychlorinated biphenyls (PCBs) are anthropogenic organochlorine compounds previously used in various industrial and chemical applications prior to being banned in the Western world in the 1970s. Both PFCs and PCBs are persistent contaminants within the human organism and both have been linked to adverse health sequelae. Data is lacking on effective means to facilitate clearance of PFCs and PCBs from the body. Methods. Blood, urine, and sweat were collected from 20 individuals (10 healthy participants and 10 participants with assorted health problems) and analyzed for PFCs and PCBs using high performance liquid chromatography tandem mass spectrometry. Results. Some individual PCB congeners, but not all, were released into sweat at varying concentrations. None of the PFCs found in serum testing appeared to be excreted efficiently into perspiration. Conclusions. Induced perspiration may have some role in facilitating elimination of selected PCBs. Sweat analysis may be helpful in establishing the existence of some accrued PCBs in the human body. Sweating does not appear to facilitate clearance of accrued PFHxS (perfluorohexane sulfonate), PFOS (perfluorooctane sulfonate), or PFOA (perfluorooctanoic acid), the most common PFCs found in the human body.