Red wine and components flavonoids inhibit UGT2B17 in vitro

Background The metabolism and excretion of the anabolic steroid testosterone occurs by glucuronidation to the conjugate testosterone glucuronide which is then excreted in urine. Alterations in UGT glucuronidation enzyme activity could alter the rate of testosterone excretion and thus its bioavailability. The aim of this study is to investigate if red wine, a common dietary substance, has an inhibitory effect on UGT2B17. Methods Testosterone glucuronidation was assayed using human UGT2B17 supersomes with quantification of unglucuronidated testosterone over time using HPLC with DAD detection. The selected red wine was analysed using HPLC and the inhibitory effects of the wine and phenolic components were tested independently in a screening assay. Further analyses were conducted for the strongest inhibitors at physiologically relevant concentrations. Control experiments were conducted to determine the effects of the ethanol on UGT2B17. Results Over the concentration range of 2 to 8% the red wine sample inhibited the glucuronidation of testosterone by up to 70% over 2 hours. The ethanol content had no significant effect. Three red wine phenolics, identified by HLPC analyses, also inhibited the enzyme by varying amounts in the order of quercetin (72%), caffeic acid (22%) and gallic acid (9%); using a ratio of phenolic:testosterone of 1:2.5. In contrast p-coumaric acid and chlorogenic acid had no effect on the UGT2B17. The most active phenolic was selected for a detailed study at physiologically relevant concentrations, and quercetin maintained inhibitory activity of 20% at 2 M despite a ten-fold excess of testosterone. Conclusion This study reports that in an in vitro supersome-based assay, the key steroid-metabolising enzyme UGT2B17 is inhibited by a number of phenolic dietary substances and therefore may reduce the rate of testosterone glucuronidation in vivo. These results highlight the potential interactions of a number of common dietary compounds on testosterone metabolism. Considering the variety of foodstuffs that contain flavonoids, it is feasible that diet can elevate levels of circulating testosterone through reduction in urinary excretion. These results warrant further investigation and extension to a human trial to delineate the healt

Utjecaj toksičnosti metala na reprodukcijsku funkciju u muškaraca

A combination of genetic, environmental and lifestyle factors contributes to adverse effects on the reproductive health in men. Metals are pervasive in food, water, air, tobacco smoke, and alcoholic beverages. Experimental studies suggest that many metals have adverse effects on the male reproductive function. However, information about reproductive effects of human exposure to metals is scarce and/or inconsistent. This review summarises the information from epidemiological studies of the effects of metal exposure on reproductive function in men. Factors capable of affecting these relationships were identifi ed and discussed. A particular attention is given to the studies considering influence of concomitant exposure to various metals. These studies have generally confirmed that even moderate- to low-level exposure to lead affects certain reproductive parameters, and that exposure to cadmium affects the prostate function and serum testosterone levels. Adverse effects of mercury, manganese, chromium and arsenic on semen quality and altered serum hormone are less well documented. There is no clear evidence that boron exposure may impair reproductive health in men. Only a few studies have investigated reproductive effects of concomitant exposure to several metals and controlled for potential confounders. Future studies should consider the contribution of combined exposure to various metals and/or other factors that may influence individual susceptibility to reproductive health impairment in men.Postoje indikacije da kombinacija genetskih, okolišnih i čimbenika načina života pridonosi uočenom poremećaju reprodukcijskog zdravlja u muškaraca. Metali su široko rasprostranjeni u čovjekovu okolišu te u hrani, vodi, zraku, cigaretnom dimu i alkoholnim pićima. Rezultati eksperimentalnih istraživanja sugeriraju štetne učinke većine ispitivanih metala na mušku reprodukcijsku funkciju. Međutim, odgovarajuća su istraživanja u ljudi oskudna. Ovaj rad sažima rezultate dosadašnjih epidemioloških istraživanja o učincima izloženosti metalima na mušku reprodukcijsku funkciju. Poseban naglasak dan je istraživanjima koja su razmatrala utjecaj istodobne izloženosti različitim metalima uz čimbenike čovjekova načina života i njihovo međudjelovanje na reprodukcijske učinke. Objavljeni rezultati daju dovoljno dokaza o štetnom djelovanju olova i žive na neke reprodukcijske parametre te kadmija na poremećaj prostate i razinu testosterona u serumu, čak u uvjetima umjerene do niske razine izloženosti. Manje je dokaza o štetnom djelovanju na kvalitetu sjemena i razinu spolnih hormona nađeno za mangan. Podaci koji upućuju na moguće štetno djelovanje arsena ili kroma nisu dosljedni, dok o štetnom djelovanju bora na mušku reprodukcijsku funkciju nema jasnih podataka. Utjecaj potencijalno uzročnih varijabli uzet je u obzir samo u nekoliko radova. Stoga buduća istraživanja poremećaja reprodukcijskog zdravlja u muškaraca trebaju razmatrati doprinos istovremene izloženosti različitim metalima koji u kombinaciji s ostalim čimbenicima mogu utjecati na osobnu (pre)osjetljivost

Systematic Review of Potential Health Risks Posed by Pharmaceutical, Occupational and Consumer Exposures to Metallic and Nanoscale Aluminum, Aluminum Oxides, Aluminum Hydroxide and Its Soluble Salts

Aluminum (Al) is a ubiquitous substance encountered both naturally (as the third most abundant element) and intentionally (used in water, foods, pharmaceuticals, and vaccines); it is also present in ambient and occupational airborne particulates. Existing data underscore the importance of Al physical and chemical forms in relation to its uptake, accumulation, and systemic bioavailability. The present review represents a systematic examination of the peer-reviewed literature on the adverse health effects of Al materials published since a previous critical evaluation compiled by Krewski et al. (2007). Challenges encountered in carrying out the present review reflected the experimental use of different physical and chemical Al forms, different routes of administration, and different target organs in relation to the magnitude, frequency, and duration of exposure. Wide variations in diet can result in Al intakes that are often higher than the World Health Organization provisional tolerable weekly intake (PTWI), which is based on studies with Al citrate. Comparing daily dietary Al exposures on the basis of “total Al”assumes that gastrointestinal bioavailability for all dietary Al forms is equivalent to that for Al citrate, an approach that requires validation. Current occupational exposure limits (OELs) for identical Al substances vary as much as 15-fold. The toxicity of different Al forms depends in large measure on their physical behavior and relative solubility in water. The toxicity of soluble Al forms depends upon the delivered dose of Al+ 3 to target tissues. Trivalent Al reacts with water to produce bidentate superoxide coordination spheres [Al(O2)(H2O4)+ 2 and Al(H2O)6 + 3] that after complexation with O2•−, generate Al superoxides [Al(O2•)](H2O5)]+ 2. Semireduced AlO2• radicals deplete mitochondrial Fe and promote generation of H2O2, O2 • − and OH•. Thus, it is the Al+ 3-induced formation of oxygen radicals that accounts for the oxidative damage that leads to intrinsic apoptosis. In contrast, the toxicity of the insoluble Al oxides depends primarily on their behavior as particulates. Aluminum has been held responsible for human morbidity and mortality, but there is no consistent and convincing evidence to associate the Al found in food and drinking water at the doses and chemical forms presently consumed by people living in North America and Western Europe with increased risk for Alzheimer\u27s disease (AD). Neither is there clear evidence to show use of Al-containing underarm antiperspirants or cosmetics increases the risk of AD or breast cancer. Metallic Al, its oxides, and common Al salts have not been shown to be either genotoxic or carcinogenic. Aluminum exposures during neonatal and pediatric parenteral nutrition (PN) can impair bone mineralization and delay neurological development. Adverse effects to vaccines with Al adjuvants have occurred; however, recent controlled trials found that the immunologic response to certain vaccines with Al adjuvants was no greater, and in some cases less than, that after identical vaccination without Al adjuvants. The scientific literature on the adverse health effects of Al is extensive. Health risk assessments for Al must take into account individual co-factors (e.g., age, renal function, diet, gastric pH). Conclusions from the current review point to the need for refinement of the PTWI, reduction of Al contamination in PN solutions, justification for routine addition of Al to vaccines, and harmonization of OELs for Al substances

Association between arsenic exposure and biomarkers of type 2 diabetes mellitus in a Croatian population: A comparative observational pilot study.

Chronic exposure to high inorganic As levels in drinking water has been related to many diseases, including type 2 diabetes mellitus (T2D). The association with low and moderate As levels, however, remains controversial and has yet not been studied in European populations.This study aimed to investigate possible association between As exposure and biomarkers of T2D in Croatian population. Observation recruited 86 adults from Eastern Croatia, where groundwater is contaminated with inorganic As, and 116 adults from Western Croatia, where As levels in drinking water are low. Both populations were divided in patient groups (T2D or prediabetes) and healthy controls. Exposure was assessed by determining total As in blood and urine and As metabolites in urine.Eastern Croatian population had a significantly higher content of As in urine than Western, whereas the opposite was true for arsenobetain. Total As and As metabolites in urine positively correlated with hemoglobin A1c (HbA1c) and negatively with albuminuria.This study provides important preliminary data on the levels of As in urine and blood and their association with biomarkers of T2D in Croatian population exposed to low or moderate levels of As through drinking water as a solid basis for further research of the pathophysiological effects of such As exposure on the status and complications of diabetes

Vitality and detoxification ability of yeasts in naturally As-rich musts

Considering the carcinogenic risk to human health, it is necessary to carry out research into arsenic (As) content in agro-food products and the impact of food processing on the final content. Yeast fermentation may represent a strategy for detoxifying some widespread beverages such as wine, beer and rice wine. A preliminary study of some commercial yeast species showed different viability responses to the presence of As. Yeasts had a noteworthy detoxification capability during fermentation, reducing the initial As content by about 75 % on average (minimum–maximum: 45–92 %), making it possible to produce wines with a considerably reduced content as compared to the corresponding grape juices from naturally As-rich soils. Nevertheless, significant differences between strains were observed in relation to resistance to arsenic toxicity and As removal capability. The choice of yeast strain can determine a difference of 40 % on the As content remaining in the wine after fermentation. Arsenic content of up to 1000 µg/L did not significantly worsen the fermentation of some wine yeasts, suggesting that the use of specific yeasts may represent an effective tool for reducing As in fermented beverage