Subchronic exposure to 1,2-naphthoquinone induces adipose tissue inflammation and changes the energy homeostasis of mice, partially due to TNFR1 and TLR4.

Air pollution affects energy homeostasis detrimentally. Yet, knowledge of how each isolated pollutant can impact energy metabolism remains incomplete. The present study was designed to investigate the distinct effects of 1,2-naphthoquinone (1,2-NQ) on energy metabolism since this pollutant increases at the same rate as diesel combustion. In particular, we aimed to determine in vivo effects of subchronic exposure to 1,2-NQ on metabolic and inflammatory parameters of wild-type mice (WT) and to explore the involvement of tumor necrosis factor receptor 1 (TNFR1) and toll-like receptor 4 (TLR4) in this process. Males WT, TNFR1KO, and TLR4KO mice at eight weeks of age received 1,2-NQ or vehicle via nebulization five days a week for 17 weeks. In WT mice, 1,2-NQ slightly decreased the body mass compared to vehicle-WT. This effect was likely due to a mild food intake reduction and increased energy expenditure (EE) observed after six weeks of exposure. After nine weeks of exposure, we observed higher fasting blood glucose and impaired glucose tolerance, whereas insulin sensitivity was slightly improved compared to vehicle-WT. After 17 weeks of 1,2-NQ exposure, WT mice displayed an increased percentage of M1 and a decreased (p = 0.057) percentage of M2 macrophages in adipose tissue. The deletion of TNFR1 and TLR4 abolished most of the metabolic impacts caused by 1,2-NQ exposure, except for the EE and insulin sensitivity, which remained high in these mice under 1,2-NQ exposure. Our study demonstrates for the first time that subchronic exposure to 1,2-NQ affects energy metabolism in vivo. Although 1,2-NQ increased EE and slightly reduced feeding and body mass, the WT mice displayed higher inflammation in adipose tissue and impaired fasting blood glucose and glucose tolerance. Thus, in vivo subchronic exposure to 1,2-NQ is harmful, and TNFR1 and TLR4 are partially involved in these outcomes.

Effects of isolated and combined exposures of Boana curupi (Anura: Hylidae) tadpoles to environmental doses of trichlorfon and ultraviolet radiation.

The biodiversity collapse strongly affects the amphibian group and many factors have been pointed out as catalytic agents. It is estimated that several events in the amphibian population decline worldwide may have been caused by the interaction of multiple drivers. Thus, this study aimed to evaluate the stressful effects of the exposure to environmental doses of trichlorfon (TCF) pesticide (0.5 µg/L; and an additional 100-fold concentration of 50 µg/L) and ultraviolet radiation (UV) (184.0 kJ/m² of UVA and 3.4 kJ/m² of UVB, which correspond to 5% of the daily dose) in tadpoles of the Boana curupi species (Anura: Hylidae). The isolated and combined exposures to TCF happened within 24 h of acute treatments under laboratory-controlled conditions. In the combined treatments, we adopted three different moments (M) of tadpole irradiation from the beginning of the exposures to TCF (0 h - M1; 12 h - M2; and 24 h - M3). Then, we evaluated tadpole survival, change in morphological characters, induction of apoptotic cells, lipid peroxidation (LPO), protein carbonyl content (PCC), glutathione S-transferase (GST), non-protein thiols (NPSH), and acetylcholinesterase (AChE), as well as the induction of genomic DNA (gDNA) damage. UVB treatment alone resulted in high mortality, along with a high level of apoptosis induction. Both UVA, UVB, and TCF increased LPO, PC, and AChE, while decreased GST activity. Regarding co-exposures, the most striking effect was observed in the interaction between UVB and TCF, which surprisingly decreased UVB-induced tadpole mortality, apoptosis, and gDNA damage. These results reinforce the B. curupi sensitivity to solar UVB radiation and indicate a complex response in face of UVB interaction with TCF, which may be related to activation of DNA repair pathways and/or inhibition of apoptosis, decreasing UVB-induced tadpole mortality.

Whole-exome sequencing reveals the impact of UVA light mutagenesis in xeroderma pigmentosum variant human cells.

UVA-induced mutagenesis was investigated in human pol eta-deficient (XP-V) cells through whole-exome sequencing. In UVA-irradiated cells, the increase in the mutation frequency in deficient cells included a remarkable contribution of C>T transitions, mainly at potential pyrimidine dimer sites. A strong contribution of C>A transversions, potentially due to oxidized bases, was also observed in non-irradiated XP-V cells, indicating that basal mutagenesis caused by oxidative stress may be related to internal tumours in XP-V patients. The low levels of mutations involving T induced by UVA indicate that pol eta is not responsible for correctly replicating T-containing pyrimidine dimers, a phenomenon known as the 'A-rule'. Moreover, the mutation signature profile of UVA-irradiated XP-V cells is highly similar to the human skin cancer profile, revealing how studies involving cells deficient in DNA damage processing may be useful to understand the mechanisms of environmentally induced carcinogenesis.