Journal of Applied Toxicology最新文献

Siloxanes, commonly known as silicones, are polymeric compounds made up of silicon and oxygen atoms bonded together alternately. Within this group of substances are linear methyl-siloxanes and cyclic methyl-siloxanes, with octamethylcyclotetrasiloxane (D4) and decamethylcyclopentasiloxane (D5) being the most produced and used industrially. Due to their versatility, high production volume, stability, and local presence in environmental matrices and biological fluids such as breast milk, fat, and plasma, siloxanes have been considered persistent organic pollutants, representing a public health problem. This represents a public health concern, especially when different investigations have reported potential endocrine effects at the reproductive level in experimental animals exposed to D4 and D5. The objective of this study was to review the potential reproductive and endocrine effects derived from siloxanes present in personal care products (PCPs). The results of the literature review confirmed that D4 and D5 were the most used siloxanes as additives in PCP because they improve the emollient properties of the cosmetic and the physical appearance of hair and skin. Similarly the toxicological effects of siloxanes, particularly D4, D5, and D6 included significant endocrine disruption, reproductive toxicity, and liver toxicity. Studies in SD and F-344 rats, commonly used to assess these effects, have shown that D4 has low estrogenic activity, binding to ER-α receptors, whereas D5 does not bind to estrogen receptors. D4 exposure has been associated with increased uterine weight and estrous cycle alterations, leading to prolonged exposure to estrogens, which raises the risk of endometrial hyperproliferation and carcinogenesis. Recent research highlights that D5 exposure disrupts follicle growth, endometrial receptivity, and steroidogenesis, resulting in infertility and hormonal imbalances, potentially causing disorders like endometriosis and increased cancer risk. Chronic exposure to D5 has been linked to the development of uterine endometrial adenocarcinoma, with higher doses further elevating this risk.

The CYP33 family in Caenorhabditis elegans is integral to processes like xenobiotic detoxification, eicosanoid regulation, nanotoxicity response and spermatogenesis. Limited research on C. elegans CYP33 suggests its functions are similar to human CYP33, indicating conserved roles in metabolism and disease. This review examines C. elegans CYP33 enzymes, especially CYP-33E1 and CYP-33E2, and their human homologues, focusing on their roles in eicosanoid biosynthesis, xenobiotic metabolism, nanotoxicity and spermatogenesis. Understanding these enzymes enhances insights into cytochrome P450 biology, metabolism and cyp-associated diseases.

Despite the continued clinical application of traditional herbal medicines, scientific evidence such as toxicological safety profile of Yongdamsagan-tang water extract (YSTW) has not yet been established. The purpose of this study was to investigate the potential toxicity profile of YSTW following a 13-week repeated oral administration at various concentrations to Sprague Dawley rats. YSTW was administered orally to rats once daily at doses of 0, 1000, 2000, and 5000 mg/kg bw/day for 13 weeks. During the experimental period, there were no significant toxicological changes related to YSTW treatment. These results indicate that the administration of YSTW for 13 weeks in the rat resulted in no signs of toxicity at up to 5000 mg/kg bw/day, which was considered the no-observed-adverse-effect level.

The success of graphene oxides has gained extensive research interests in developing novel 2D nanomaterials (NMs). WS₂ nanosheets (NSs) are novel transition metal-based 2D NMs, but their toxicity is unclear. In this study, we investigated the oral toxicity of WS₂ NSs to mouse intestines. Male mice were administrated with vehicles, 1, 10, or 100 mg/kg NSs via intragastric route, once a day, for 5 days. The results indicate that the NSs did not induce pathological or ultrastructural changes in intestines. There were minimal changes of trace elements that the exposure did not induce W accumulation, and only Co levels were dose-dependently increased. Lipid droplets were observed in all groups of mice, but lipidomics data indicate that WS₂ NSs only significantly decreased four lipid species, all belonging to phosphatidylcholine (PC). The levels of proteins regulating autophagic lipolysis, namely, LC3, lysosomal associated membrane protein 2 (LAMP2) and perilipin 2 (PLIN2), were increased, but it was only statistically significantly different for LC3. The results of this study suggest that repeated intragastric exposure to WS₂ NSs only induced minimal influences on pathological injury, trace element balance, autophagy, and lipid profiles in mouse intestines, indicating relatively high biocompatibility of WS₂ NSs to mouse intestine via oral route.

Cumulative evidence suggested that nanoplastics (NPs) cause male toxicity, but the mechanisms of which are still misty. Steroidogenesis is a key biological event that responsible for maintaining reproductive health. However, whether dysregulated steroidogenesis is involved in NPs-induced impaired male reproductive function and the underlying mechanism remains unclear. In our study, Balb/c mice were continuously exposed to pristine-NPs or NH₂-NPs for 12 weeks, spanning the puberty and adult stage. Upon the long-term NPs treatment, the hypothalamus and testis were subjected to transcriptome and metabolome analysis. And the results demonstrated that both primitive-NPs and NH₂-NPs resulted in impaired spermatogenesis and steroidogenesis, as evidenced by a significant reduction in sperm quality, testosterone, FSH, and LH. The expression of genes involved in hypothalamic-pituitary-testis (HPT) axis, such as Kiss-1 and Cyp17a1 that encoded the key steroid hormone synthetase, was also diminished. Furthermore, the phosphatidylcholine and pantothenic acid that mainly enriched in glycerophospholipid metabolism were significantly reduced in the testis. Comprehensive analysis of the transcriptome and metabolome indicated that down-regulated Cyp17a1 was associated with decreased metabolites phosphatidylcholine and pantothenic acid. Overall, we speculate that the disturbed HPT axis induced by long-term NPs contributes to disordered glycerophospholipid metabolism and subsequently impaired steroidogenesis. Our findings deepen the understanding of the action of the mechanism responsible for NPs-induced male reproductive toxicology.

The preceding decades have seen an extensive emergence of the harmful effects of tobacco smoke on systemic health. Among the various compounds of tobacco, nicotine is one of the principal, potentially hazardous, and toxic components which is an oxidant agent that can affect both men's and women's fertility. Nicotine exerts its effect by modulating the expression of transmembrane ligand-gated ion channels called nicotinic acetylcholine receptors. The activities of female reproduction might be disrupted by exposure to nicotine at various sites, such as the ovary or reproductive tract. It's been demonstrated that nicotine might cause oxidative stress, apoptosis, hormonal imbalance, abnormalities in chromosomal segregation, impact oocyte development, and disruption in ovarian morphology and functions. This review paper summarizes the findings and provides an updated overview of the evidence on the harmful effects of nicotine use on women's reproductive health and the resulting detrimental impacts on the body. Additionally, it provides the detailed possible mechanisms involved in impairing reproductive processes like folliculogenesis, oocyte maturation, steroidogenesis, and pregnancy in different animal species.

The reliability of relative quantification RT-qPCR depends upon the gene of interest being normalized to one or more reference genes, with the assumption that the chosen reference genes do not experience altered expression with experimental conditions. The correct choice of stable reference genes is critical when investigating alterations to gene transcript levels following exposure to endocrine and metabolic disrupting chemicals, such as the flame retardant triphenyl phosphate (TPhP). This study assessed the stability of eight reference genes following TPhP exposure in embryonic cells derived from rainbow trout (Oncorhynchus mykiss). The genes β-actin (actb) and 18s rRNA (18s) were stable, while glyceraldehyde-3-phosphate dehydrogenase (gapdh) relative expression was found to be increased. gapdh is a popular reference gene and has been previously used in the literature for investigating TPhP exposure in teleost fish models. We discuss the implications of gapdh upregulation in the context of TPhP as a metabolic disrupting chemical. Furthermore, we quantified the expression of the tumor suppressor gene p53 following TPhP exposure in relation to different reference genes to use as an example to report on how discrepancies in findings might arise depending on the stability of the chosen reference gene.

Hexabromocyclododecane (HBCD) is an environmental contaminant due to its use as a flame retardant in a variety of applications ranging from building insulation, furniture upholstery, and housing for appliances and electronics. HBCD is found in wildlife, human breastmilk, and serum. Interleukin 1-beta (IL-1β) and interleukin 6 (IL-6) are pro-inflammatory cytokines, whose dysregulation is associated with chronic inflammation and the pathologies that result, such as tumor growth, rheumatoid arthritis, Crohn's disease, and multiple sclerosis. HBCD has been shown to increase the secretion of both IL-1β and IL-6 from human immune cells. However, it is not clear if these increases are due solely to HBCD effects on the secretory process or whether it is stimulating cellular production of IL-1β and IL-6. This study examines if HBCD can increase the production of IL-1β and IL-6 by immune cells by simultaneously assessing secreted levels and cellular levels of these cytokines. Additionally, the mechanisms for any observed changes in production are investigated. Peripheral blood mononuclear cells were exposed to HBCD over a range of concentrations and lengths of exposure. HBCD was found to stimulate IL-1β and IL-6 production after 6 hrs. of exposure and production was sustained and intensified at 24 hrs. This increase in IL-1β and IL-6 production appears to, in part, be a result of increased mRNA expression. Additionally, the MAPK pathways, specifically the p38 and p44/42 pathways, appear to be required for HBCD-induced increases in IL-1β and IL-6 production.