ABSTRACT
Microplastics (MPs) and benzo[a]pyrene (B[a]P) are prevalent environmental pollutants. Numerous studies have extensively reported their individual adverse effects on organisms. However, the combined effects and mechanisms of exposure in mammals remain unknown. Thus, this study aims to investigate the potential effects of oral administration of 0.5µm polystyrene (PS) MPs (1â¯mg/mL or 5â¯mg/mL), B[a]P (1â¯mg/mL or 5â¯mg/mL) and combined (1â¯mg/mL or 5â¯mg/mL) on 64 male SD rats by gavage method over 6-weeks. The results demonstrate that the liver histopathological examination showed that the liver lobules in the combined (5â¯mg/kg) group had blurred and loose boundaries, liver cord morphological disorders, and significant steatosis. The levels of AST, ALT, TC, and TG in the combined dose groups were significantly higher than those in the other groups, the combined (5â¯mg/kg) group had the lowest levels of antioxidant enzymes and the highest levels of oxidants. The expression of Nrf2 was lowest and the expression of P38, NF-κB, and TNF-α was highest in the combined (5â¯mg/kg) group. In conclusion, these findings indicate that the combination of PSMPs and B[a]P can cause the highest levels of oxidative stress and elicit markedly enhanced toxic effects, which cause severe liver damage.
Subject(s)
Benzo(a)pyrene , Liver , Microplastics , Oxidative Stress , Polystyrenes , Rats, Sprague-Dawley , Animals , Oxidative Stress/drug effects , Benzo(a)pyrene/toxicity , Microplastics/toxicity , Male , Polystyrenes/toxicity , Liver/drug effects , Liver/pathology , Rats , Environmental Pollutants/toxicity , Antioxidants/metabolism , NF-kappa B/metabolism , NF-E2-Related Factor 2/metabolismABSTRACT
BACKGROUND: Previous observational studies have established the high prevalence of bacterial pneumonia in diabetic patients, which in turn leads to increased mortality. However, the presence of a causal connection between bacterial pneumonia and diabetes remains unobserved. METHODS: We chose genome-wide significant (Ρ < 1 × 10-5 and Ρ < 1 × 10-6) and independent (r2 < 0.001) single-nucleotide polymorphisms (SNPs) as instrumental variables (IVs) to proceed a bidirectional two-sample MR study. The extracted SNPs explored the relationship between bacterial pneumonia and diabetes by Inverse variance weighted (IVW), MR-Egger, and weighted median methods. In addition, we conducted the Heterogeneity test, the Pleiotropy test, MR-presso and the Leave-one-out (LOO) sensitivity test to validate the reliability of results. RESULTS: In an MR study with bacterial pneumonia as an exposure factor, four different types of diabetes as outcome. It was observed that bacterial pneumonia increases the incidence of GDM (OR = 1.150 (1.027-1.274, P = 0.011) and T1DM (OR = 1.277 (1.024-1.531), P = 0.016). In the reverse MR analysis, it was observed that GDM (OR = 1.112 (1.023-1.201, P = 0.009) is associated with an elevated risk of bacterial pneumonia. However, no significant association was observed bacterial pneumonia with T1DM and other types of diabetes (P > 0.05). CONCLUSION: This study utilizing MR methodology yields robust evidence supporting a bidirectional causal association between bacterial pneumonia and GDM. Furthermore, our findings suggest a plausible causal link between bacterial pneumonia and T1DM.