Inflammation response, oxidative stress and DNA damage caused by urban air pollution exposure increase in the lack of DNA repair XPC protein.

Air pollution represents a considerable threat to health worldwide. The São Paulo Metropolitan area, in Brazil, has a unique composition of atmospheric pollutants with a population of nearly 20 million people and 9 million passenger cars. It is long known that exposure to particulate matter less than 2.5 µm (PM2.5) can cause various health effects such as DNA damage. One of the most versatile defense mechanisms against the accumulation of DNA damage is the nucleotide excision repair (NER), which includes XPC protein. However, the mechanisms by which NER protects against adverse health effects related to air pollution are largely unknown. We hypothesized that reduction of XPC activity may contribute to inflammation response, oxidative stress and DNA damage after PM2.5 exposure. To address these important questions, XPC knockout and wild type mice were exposed to PM2.5 using the Harvard Ambient Particle concentrator. Results from one-single exposure have shown a significant increase in the levels of anti-ICAM, IL-1ß, and TNF-α in the polluted group when compared to the filtered air group. Continued chronic PM2.5 exposure increased levels of carbonylated proteins, especially in the lung of XPC mice, probably as a consequence of oxidative stress. As a response to DNA damage, XPC mice lungs exhibit increased γ-H2AX, followed by severe atypical hyperplasia. Emissions from vehicles are composed of hazardous substances, with polycyclic aromatic hydrocarbons (PAHs) and metals being most frequently cited as the major contributors to negative health impacts. This analysis showed that benzo[b]fluoranthene, 2-nitrofluorene and 9,10-anthraquinone were the most abundant PAHs and derivatives. Taken together, these findings demonstrate the participation of XPC protein, and NER pathway, in the protection of mice against the carcinogenic potential of air pollution. This implicates that DNA is damaged directly (forming adducts) or indirectly (Reactive Oxygen Species) by the various compounds detected in urban PM2.5.

Concentrated ambient fine particulate matter (PM2.5) exposure induce brain damage in pre and postnatal exposed mice.

Air pollution is a public health concern that has been associated with adverse effects on the development and functions of the central nervous system (CNS). However, studies on the effects of exposure to pollutants on the CNS across the entire developmental period still remain scarce. In this study, we investigated the impacts of prenatal and/or postnatal exposure to fine particulate matter (PM2.5) from São Paulo city, on the brain structure and behavior of juvenile male mice. BALB/c mice were exposed to PM2.5 concentrated ambient particles (CAP) at a daily concentration of 600 µg/m³ during the gestational [gestational day (GD) 1.5-18.5] and the postnatal periods [postnatal day (PND) 22-90] to filtered air (FA) in both periods (FA/FA), to CAP only in the postnatal period (FA/CAP), to CAP only in the gestational period (CAP/FA), and to CAP in both periods (CAP/CAP). Behavioral tests were performed when animals were at PND 30 and PND 90. Glial activation, brain volume, cortical neuron number, serotonergic and GABAergic receptors, as well as oxidative stress, were measured. Mice at PND 90 presented greater behavioral changes in the form of greater locomotor activity in the FA-CAP and CAP-CAP groups. In general, these same groups explored objects longer and the CAP-FA group presented anxiolytic behavior. There was no difference in total brain volume among groups, but a lower corpus callosum (CC) volume was observed in the CAP-FA group. Also, the CAP-CAP group presented an increase in microglia in the cortex and an increased in astrocytes in the cortex, CC, and C1A and dentate gyrus of hippocampus regions. Gene expression analysis showed a decrease in BDNF in the hippocampus of CAP-CAP group. Treatment of immortalized glial cells with non-cytotoxic doses of ambient PM2.5 increased micronuclei frequencies, indicating genomic instability. These findings highlight the potential for negative neurodevelopmental outcomes induced by exposure to moderate levels of PM2.5 in Sao Paulo city.

Subchronic air pollution exposure increases highly palatable food intake, modulates caloric efficiency and induces lipoperoxidation.

The investigation of the relationship between air pollution and obesity has captured the interest of researchers. However, the mechanism regarding the association between air pollution exposure and metabolic diseases and obesity still remains unclear. We aimed to investigate the effects of subchronic ROFA exposure on consumption and preference for highly palatable food and its interference on biochemical, lipid and oxidative stress parameters in rats. Male Wistar rats were divided in groups: control, ROFA, chocolate and ROFA + chocolate. Rats were exposed to ROFA during 18 weeks and to palatable food in the last 30 days. Food consumption, caloric intake and caloric efficiency, body mass gain, abdominal fat deposition, glucose and lipid profile were measured. Thiobarbituric acid reactive substances (TBARS), catalase (CAT) and superoxide dismutase (SOD) activity were assessed in lungs, heart, pancreas and hypothalamus. Chocolate intake was higher in the first and second weeks in rats exposed to ROFA while the standard chow intake was smaller in second and third weeks. The amount of kilocalories derived from chocolate was higher in the animals exposed to ROFA in all weeks. The caloric intake and body mass gain were not different among groups. Triglycerides, total cholesterol and HDL were higher in chocolate exposed rats. The TBARS was higher in lung and heart in ROFA group and in hypothalamus in ROFA + chocolate group. There were no significant differences in glucose, LDL and antioxidant enzymes. These findings indicate that subcronic air pollution exposure can modulate metabolic effects of subacute exposure to chocolate in adulthood.

Resistance training and L-arginine supplementation are determinant in genomic stability, cardiac contractility and muscle mass development in rats.

L-arginine supplementation has been related to increased maximum strength and improvement of hemodynamic parameters in several diseases. The aim of our study was to evaluate the effect of L-arginine supplementation and resistance training on muscle mass, hemodynamic function and DNA damage in healthy rats subjected to a low-arginine concentration diet. Twenty three Wistar rats (290-320g) were divided into 4 groups: Sedentary (SED-Arg, n = 6), Sedentary+Arg (SED+Arg, n = 6), Resistance Training (RT-Arg, n = 5), Resistance Training+Arg (RT+Arg, n = 6). Trained animals performed resistance training protocol in a squat apparatus adapted for rats (4 sets of 10-12 repetitions, 90s of interval, 4x/week, 65-75% of One Maximum Repetition, for 8 weeks). Comet assay was performed to measure DNA damage in leukocytes. The resistance training induced higher muscle mass in trained groups. The L-arginine supplementation increased both gastrocnemius and left ventricle to body mass ratio and increased left ventricle contractility without changing hemodynamic variables. The SED+Arg group showed higher concentration of extracellular heat shock protein 72 (eHSP72) and total testosterone, as well as lower uric acid concentration in blood versus SED-Arg group. The administration of isolated L-arginine supplementation and its association with resistance training promoted less damage in leukocytes DNA. In conclusion, the L-arginine supplementation showed synergistic effect with resistance training regarding leukocyte genomic stability in a low-L-arginine diet scenario.

Prolactin gene expression in primary central nervous system tumors.

BACKGROUND: Prolactin (PRL) is a hormone synthesized in both the pituitary gland and extrapituitary sites. It has been associated with the occurrence of neoplasms and, more recently, with central nervous system (CNS) neoplasms. The aim of this study was to evaluate prolactin expression in primary central nervous system tumors through quantitative real-time PCR and immunohistochemistry (IH). RESULTS: Patient mean age was 49.1 years (SD 15.43), and females accounted for 70% of the sample. The most frequent subtype of histological tumor was meningioma (61.5%), followed by glioblastoma (22.9%). Twenty cases (28.6%) showed prolactin expression by immunohistochemistry, most of them females (18 cases, 90%). Quantitative real-time PCR did not show any prolactin expression. CONCLUSIONS: Despite the presence of prolactin expression by IH, the lack of its expression by quantitative real-time PCR indicates that its presence in primary tumors in CNS is not a reflex of local production.