Metformin Inhibits ROS Production by Human M2 Macrophages via the Activation of AMPK.

Metformin (1,1-dimethylbiguanide hydrochloride) is the most commonly used drug to treat type II diabetic patients. It is believed that this drug has several other beneficial effects, such as anti-inflammatory and anticancer effects. Here, we wanted to evaluate the effect of metformin on the production of reactive oxygen species (ROS) by human macrophages. Macrophages are generated in vivo from circulating monocytes depending on the local tissue environment. In vitro proinflammatory macrophages (M1) and anti-inflammatory macrophages (M2) can be generated by culturing monocytes in the presence of different cytokines, such as GM-CSF or M-CSF, respectively. We show that metformin selectively inhibited human monocyte differentiation into proinflammatory macrophages (M1) without inhibiting their differentiation into anti-inflammatory macrophages (M2). Moreover, we demonstrate that, in response to LPS, M2 macrophages produced ROS, which could be very harmful for nearby tissues, and metformin inhibited this process. Interestingly, metformin with LPS induced activation of the adenosine-monophosphate-activated protein kinase (AMPK) and pharmacological activation of AMPK by AICAR, a known AMPK activator, decreased ROS production, whereas the deletion of AMPK in mice dramatically enhanced ROS production in different types of immune cells. These results suggest that metformin exhibits anti-inflammatory effects by inhibiting the differentiation of human monocytes into M1 macrophages and by limiting ROS production by macrophages via the activation of AMPK.

Mercury health risk assessment among a young adult Lebanese population.

Mercury (Hg) exposure represents a significant public health concern at a global level. This study aims at assessing Hg exposure and risk among Lebanese young adults based on Hg biomonitoring and seafood intake. A group of 166 young adults were administered a questionnaire to assess Hg exposure and were asked to provide a hair sample. Risk assessment was performed: (1) using the US Environmental Protection Agency Hazard Quotient (HQ) model based on fish intake and previously studied local fish Hg concentrations, and (2) by determining the total hair Hg concentration (THHg) using continuous flow-chemical vapor generation atomic absorption spectrometry. Differences in THHg across demographic and exposure subgroups were tested using t test or ANOVA. Correlations between THHg concentrations, fish consumption, and HQ were determined by computing Pearson's r. Higher THHg correlated with higher consumption of Mediterranean rabbitfish/spinefoots (r = 0.27; p = 0.001) and geographical location (p < 0.001) in the bivariate analysis, and remained significant in the adjusted multivariable linear regression model (geographical location: ß = 0.255, 95%CI 0.121-0.388; rabbitfish/spinefoots consumption: ß = 0.016, 95%CI 0.004-0.027). No significant correlations were found between HQ and THHg. In conclusion, this is the first study examining hair Hg levels and fish consumption in a young adult Lebanese population. Our findings constitute valuable baseline data for a local fish advisory and Hg monitoring.

Exposure assessment of endocrine disruptors in bottled drinking water of Lebanon.

Bisphenol A (BPA) is a commonly used monomer in various products including bottled water. Numerous studies have reported endocrine adverse effects and neoplasia associated with BPA exposure in animals. However, considerable discrepancies exist among these studies with respect to both the nature of the toxic effects and the threshold dose. In Lebanon, 19-L polycarbonate (PC) bottles of drinking water are widely used in urban areas. The present study aims at assessing BPA human exposure and associated health risks from drinking water in Lebanese. A total of 22 bottled water sources, packaged in PC, were identified from licensed and non-licensed sources. Water samples were analyzed following exposure to sunlight for 72 h. BPA in water was quantified by HPLC, and other potential organic pollutants were screened by GC/MS. Fifty-nine percent of samples showed BPA levels above detection limits (>0.05 ng/mL). The median BPA level was 0.1 ng/mL (range 0.05 to 1.37 ng/mL). The mean BPA level for the total number of samples was 0.169 ng/mL (±0.280). A higher mean BPA level was found in water from licensed companies compared to non-licensed sources, however, not statistically significant. Screening showed the presence of dibutyl-phthalate and dioctyl-phthalate in only two samples. Endocrine disruptors (EDR) are ubiquitous contaminants in bottled water in Lebanon with potential health risk implications. Although estimated exposure levels are below the reference dose (RfD), further studies are needed to quantitate exposure from various sources and to investigate EDR contribution to existing epidemics in the country.