The hepatoprotective effects of Herbt Tea Essences on phenanthrene-induced liver damage in mice.

Phenanthrene (Phe), one of the most frequently occurring pollutants in nature, can cause substantial damage to the human liver. Herbt Tea Essences (HTE), a kind of black tea extract with strong anti-inflammatory activity, can protect humans against disease. Currently, whether HTE can protect the liver from Phe-induced hepatotoxicity remains unclear. Herein, we explore the protective effects of HTE against Phe-induced hepatotoxicity. Our results showed that Phe exposure could significantly induce liver damage and increase serum hepatic enzyme levels in mice. HTE could prevent liver damage and recover the expression levels of inflammatory factors. Furthermore, we found that HTE suppressed the excessive activation of the nuclear transcription factor kappa-B and transforming growth factor-ß/SMAD signaling pathways to alleviate Phe-induced liver inflammation and fibrosis. Overall, our data showed that HTE treatment could be a new preventive means for Phe-induced liver disease.

Estradiol protects female mice from hyperuricemia induced by PCB138 exposure.

Polychlorinated biphenyls (PCBs) are a type of persistent organic pollutant (POP). Our previous study demonstrated that exposure to 0.5-50 µg/kg bw PCB138 during postnatal days (PND) 3-21 led to elevated serum uric acid (UA) levels and kidney injury in adult male mice. Given that the prevalence of hyperuricemia (HUA) is significantly lower in women than in men, it is worth investigating whether POP-induced HUA and its secondary kidney injury have sexual dimorphism. Herein, we exposed female mice to 0.5-50 µg/kg bw PCB138 during PND 3-21, resulting in elevated serum UA levels, but without causing significant kidney damage. Concurrently, we found a negative correlation between serum 17ß-estradiol (E2) and serum UA levels. We also observed down-regulation of estrogen receptor (ER) protein levels in the kidneys of the PCB138-exposed groups. Furthermore, our study showed that E2 rescued the increased UA level and cytotoxicity caused by HUA in human renal tubular epithelial (HK-2) cells. Collectively, our findings suggest that E2 likely plays a crucial protective role in PCB138-induced HUA and kidney injury in female mice. Our research highlights the existence of sexual dimorphism in kidney injury secondary to HUA induced by POPs, which could provide guidance for individuals of different genders in preventing kidney injury caused by environmental factors.

Multi-omics integration identifies ferroptosis involved in black phosphorus quantum dots-induced renal injury.

Black phosphorus quantum dots (BPQDs) have recently emerged as a highly promising contender in biomedical applications ranging from drug delivery systems to cancer therapy modalities. Nevertheless, the potential toxicity and its effects on human health need to be thoroughly investigated. In this study, we utilized multi-omics integrated approaches to explore the complex mechanisms of BPQDs-induced kidney injury. First, histological examination showed severe kidney injury in male mice after subacute exposure to 1 mg/kg BPQDs for 28 days. Subsequently, transcriptomic and metabolomic analyses of kidney tissues exposed to BPQDs identified differentially expressed genes and metabolites associated with ferroptosis, an emerging facet of regulated cell death. Our findings highlight the utility of the multi-omics integrated approach in predicting and elucidating potential toxicological outcomes of nanomaterials. Furthermore, our study provides a comprehensive understanding of the mechanisms driving BPQDs-induced kidney injury, underscoring the importance of recognizing ferroptosis as a potential toxic mechanism associated with BPQDs.

Phenanthrene-induced hyperuricemia with intestinal barrier damage and the protective role of theabrownin: Modulation by gut microbiota-mediated bile acid metabolism.

Hyperuricemia is prevalent globally and potentially linked to environmental pollution. As a typical persistent organic pollutant, phenanthrene (Phe) poses threats to human health through biomagnification. Although studies have reported Phe-induced toxicities to multiple organs, its impact on uric acid (UA) metabolism remains unclear. In this study, data mining on NHANES 2001-2016 indicated a positive correlation between Phe exposure and the occurrence of hyperuricemia in population. Subsequently, adolescent Balb/c male mice were orally exposed to Phe at a dosage of 10 mg/kg bw every second day for 7 weeks, resulting in dysfunction of intestinal UA excretion and disruption of the intestinal barrier. Utilizing intestinal organoids, 16S rRNA sequencing of gut microbiota, and targeted metabolomic analysis, we further revealed that an imbalance in bile acid metabolism derived from gut microbiota might mediate the intestinal barrier damage. Additionally, the tea extract theabrownin (TB) effectively improved Phe-induced hyperuricemia and intestinal dysfunction at a dose of 320 mg/kg bw per day. In conclusion, this study demonstrates that Phe exposure is positively associated with hyperuricemia and intestinal damage, which provides new insights into the toxic effects induced by Phe. Furthermore, the present study proposes that supplementation with TB would be a healthy and effective improvement strategy for patients with hyperuricemia and intestinal injury caused by environmental factors.

Early life PCB138 exposure induces kidney injury secondary to hyperuricemia in male mice.

Polychlorinated biphenyls (PCBs) are a class of persistent organic pollutants (POPs) that have adverse effects on human health. However, the long-term health effects and potential mechanism of neonatal exposure to PCBs are still unclear. In this study, nursing male mice exposed to PCB138 at 0.5, 5, and 50 µg/kg body weight (bw) from postnatal day (PND) 3 to PND 21 exhibited increased serum uric acid levels and liver uric acid synthase activity at 210 days of age. We also found an increased kidney somatic index in the 50 µg/kg group and kidney fibrosis in the 5 and 50 µg/kg groups. Mechanistically, PCB138 induced mitochondrial dysfunction and endoplasmic reticulum (ER) stress, which might have led to inflammatory responses, such as activation of the NF-κB (nuclear factor kappa-B) and NLRP3 (NOD-like receptor protein 3) pathways. The inflammatory response might regulate renal fibrosis and hypertrophy. In summary, this study reports a long-term effect of neonatal PCB exposure on uric acid metabolism and secondary nephrotoxicity and clarifies the underlying mechanism. Our work also indicates that early life pollutant exposure may be an important cause of diseases later in life.

Role of RNA m6A modification in titanium dioxide nanoparticle-induced acute pulmonary injury: An in vitro and in vivo study.

RNA N6-methyladenosine (m6A) modification regulates the cell stress response and homeostasis, but whether titanium dioxide nanoparticle (nTiO2)-induced acute pulmonary injury is associated with the m6A epitranscriptome and the underlying mechanisms remain unclear. Here, the potential association between m6A modification and the bioeffects of several engineered nanoparticles (nTiO2, nAg, nZnO, nFe2O3, and nCuO) were verified thorough in vitro experiments. nFe2O3, nZnO, and nTiO2 exposure significantly increased the global m6A level in A549 cells. Our study further revealed that nTiO2 can induce m6A-mediated acute pulmonary injury. Mechanistically, nTiO2 exposure promoted methyltransferase-like 3 (METTL3)-mediated m6A signal activation and thus mediated the inflammatory response and IL-8 release through the degeneration of anti-Mullerian hormone (AMH) and Mucin5B (MUC5B) mRNAs in a YTH m6A RNA-binding protein 2 (YTHDF2)-dependent manner. Moreover, nTiO2 exposure stabilized METTL3 protein by the lipid reactive oxygen species (ROS)-activated ERK1/2 pathway. The scavenging of ROS with ferrostatin-1 (Fer-1) alleviates the ERK1/2 activation, m6A upregulation, and the inflammatory response caused by nTiO2 both in vitro and in vivo. In conclusion, our study demonstrates that m6A is a potential intervention target for alleviating the adverse effects of nTiO2-induced acute pulmonary injury in vitro and in vivo, which has far-reaching implications for protecting human health and improving the sustainability of nanotechnology.