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Potentials of orally supplemented selenium-enriched Lacticaseibacillus rhamnosus to mitigate the lead induced liver and intestinal tract injury
2022
Jin, Han | Riaz Rajoka, Muhammad Shahid | Xu, Xiaoguang | Liao, Ning | Pang, Bing | Yan, Lu | Liu, Guanwen | Sun, Hui | Jiang, Chunmei | Shao, Dongyan | Barba, Francisco J. | Shi, Junling
Lead is a metal that exists naturally in the Earth's crust and is a ubiquitous environmental contaminant. The alleviation of lead toxicity is important to keep human health under lead exposure. Biosynthesized selenium nanoparticle (SeNPs) and selenium-enriched Lactobacillus rhamnosus SHA113 (Se-LRS) were developed in this study, and their potentials in alleviating lead-induced injury to the liver and intestinal tract were evaluated in mice by oral administration for 4 weeks. As results, oral intake of lead acetate (150 mg/kg body weight per day) caused more than 50 times and 100 times lead accumulation in blood and the liver, respectively. Liver function was seriously damaged by the lead exposure, which is indicated as the significantly increased lipid accumulation in the liver, enhanced markers of liver function injury in serum, and occurrence of oxidative stress in liver tissues. Serious injury in intestinal tract was also found under lead exposure, as shown by the decrease of intestinal microbiota diversity and occurrence of oxidative stress. Except the lead content in blood and the liver were lowered by 52% and 58%, respectively, oral administration of Se-LRS protected all the other lead-induced injury markers to the normal level. By the comparison with the effects of normal L. rhamnosus SHA113 and the SeNPs isolated from Se-LRS, high protective effects of Se-LRS can be explained as the extremely high efficiency to promote lead excretion via feces by forming insoluble mixture. These findings illustrate the developed selenium-enriched L. rhamnosus can efficiently protect the liver and intestinal tract from injury by lead.
اظهر المزيد [+] اقل [-]Nontarget analysis reveals gut microbiome-dependent differences in the fecal PCB metabolite profiles of germ-free and conventional mice
2021
Li, Xueshu | Liu, Yanna | Martin, Jonathan W. | Cui, Julia Yue | Lehmler, Hans-Joachim
Mammalian polychlorinated biphenyl (PCB) metabolism has not been systematically explored with nontarget high-resolution mass spectrometry (Nt-HRMS). Here we investigated the importance of the gut microbiome in PCB biotransformation by Nt-HRMS analysis of feces from conventional (CV) and germ-free (GF) adult female mice exposed to a single oral dose of an environmental PCB mixture (6 mg/kg or 30 mg/kg in corn oil). Feces were collected for 24 h after PCB administration, PCB metabolites were extracted from pooled samples, and the extracts were analyzed by Nt-HRMS. Twelve classes of PCB metabolites were detected in the feces from CV mice, including PCB sulfates, hydroxylated PCB sulfates (OH-PCB sulfates), PCB sulfonates, and hydroxylated methyl sulfone PCBs (OH-MeSO₂-PCBs) reported previously. We also observed eight additional PCB metabolite classes that were tentatively identified as hydroxylated PCBs (OH-PCBs), dihydroxylated PCBs (DiOH-PCBs), monomethoxylated dihydroxylated PCBs (MeO-OH-PCBs), methoxylated PCB sulfates (MeO-PCB sulfates), mono-to tetra-hydroxylated PCB quinones ((OH)ₓ-quinones, x = 1–4), and hydroxylated polychlorinated benzofurans (OH-PCDF). Most metabolite classes were also detected in the feces from GF mice, except for MeO-OH-PCBs, OH-MeSO₂-PCBs, and OH-PCDFs. Semi-quantitative analyses demonstrate that relative PCB metabolite levels increased with increasing dose and were higher in CV than GF mice, except for PCB sulfates and MeO-PCB sulfates, which were higher in GF mice. These findings demonstrate that the gut microbiome plays a direct or indirect role in the absorption, distribution, metabolism, or excretion of PCB metabolites, which in turn may affect toxic outcomes following PCB exposure.
اظهر المزيد [+] اقل [-]High inter-species differences of 12378-polychlorinated dibenzo-p-dioxin between humans and mice
2020
Dong, Zhaomin | Ben, Yujie | Li, Yu | Li, Tong | Wan, Yi | Hu, Jianying
Although huge interspecies differences in the response to dioxins have been acknowledged, toxic equivalency factors derived from rodent studies are often used to assess human health risk. To determine interspecies differences, we first developed a toxicokinetic model in humans by measuring dioxin concentrations in environmental and biomonitoring samples from Southern China. Significant positive correlations between dioxin concentrations in blood and age were observed for seven dioxin congeners, indicating an age-dependent elimination rate. Based on toxicokinetic models in humans, the half-lives of 15 dioxin congeners were estimated to be 1.60–28.55 years. In consideration that the highest contribution to total toxic equivalency in blood samples was by 12378-polychlorinated dibenzo-p-dioxin (P₅CDD), this study developed a physiologically based pharmacokinetic (PBPK) model of 12378-P₅CDD levels in the liver, kidney, and fat of C57/6J mice exposed to a single oral dose, and the half-life was estimated to be 26.1 days. Based on estimated half-lives in humans and mice, we determined that the interspecies difference of 12378-P₅CDD was 71, much higher than the default usually used in risk assessment. These results could reduce the uncertainty human risk assessment of 12378-P₅CDD, and our approach could be used to estimate the interspecies differences of other dioxin congeners.
اظهر المزيد [+] اقل [-]Etoxazole induces testicular malfunction in mice by dysregulating mitochondrial function and calcium homeostasis
2020
Epidemiological relationships between pesticide use and male infertility have been suggested for a long time. Etoxazole (ETX), an oxazoline pesticide, has been extensively used for pest eradication. It is considered relatively safe and has low mammalian toxicity because it specifically inhibits chitin synthesis. However, ETX may have toxic effects on the reproductive system. In this study, we examined the effects of ETX on the reproductive system using mouse testis cell lines (TM3 for Leydig cells and TM4 for Sertoli cells) and C57BL/6 male mice. We confirmed that ETX has anti-proliferative effects on the TM3 and TM4 cell lines. Moreover, ETX induced mitochondrial dysfunction and hampers calcium homeostasis. Western blot analysis of MAPK and Akt signaling cascades was performed to demonstrate the mode of action of ETX at a molecular level. Moreover, ETX induced misregulation of genes related to testicular function. Upon oral administration of ETX in C57BL/6 male mice, testis weight was reduced and transcriptional expression related to testis function was altered. These results indicate that ETX induces testicular toxicity by inducing mitochondrial dysfunction and calcium imbalance and regulating gene expression.
اظهر المزيد [+] اقل [-]Transportation and degradation of decabrominated diphenyl ether in sequential anoxic and oxic crop rotation
2020
Zhao, Pengfei | Wang, Wei | Whalen, Joann K. | Zhang, Subin | Ye, Qingfu
This work evaluated the debromination and uptake of ¹⁴C-labeled BDE-209 in rice cultivars grown in anoxic soil for 120 days (d) followed by cultivation of vegetables (peanut, eggplant and pepper) in oxic soil (120 d). Degradation of BDE-209 to lower polybrominated diphenyl ethers (PBDEs) occurred in cultivated soils, and more metabolites were released in oxic soil than in anoxic soil. The crop rotation from anoxic to oxic greatly enhanced the dissipation of BDE-209 in the soil (P < 0.05), in which the dissipation in anoxic soil planted with Huanghuazhan (HHZ, indica) and Yudao 1 (YD1, indica) were 6.8% and 2.4%, respectively, while in oxic soil with peanut and pepper were increased to 25.8% and 21.7%, respectively. The crop rotation also enhanced the degradation of BDE-209 in the soil, the recovered BDE-209 in soil after 120 d anoxic incubation with YD1 was 81.1%, but it decreased to 47.8% and 45.8% after another 120 d oxic incubation. Bioconcentration factors were between 0.23 and 0.36 for rice, eggplant and pepper but reached to 0.5 in peanut, which contains more lipids in the edible portion than the other test crops. The estimated daily intake for vegetables was 0.01–0.07 μg BDE-209-equivalent kg⁻¹ bw day⁻¹, which is at least two orders of magnitude below the maximum acceptable oral dose (7 μg kg⁻¹ bw day⁻¹). Our work confirms that crop rotation from rice to vegetable enhanced the dissipation and debromination of BDE-209 in the soil, and indicate that sequential anoxic-oxic rotation practice is considered to be effective in remediation of environmental pollutants.
اظهر المزيد [+] اقل [-]Comparative toxicokinetics and tissue distribution of prothioconazole and prothioconazole-desthio in Chinese lizards (Eremias argus) and transcriptional responses of metabolic-related genes
2019
Xie, Yun | Li, Leon Yu Zheng | Hao, Weiyu | Chang, Jing | Xu, Peng | Guo, Baoyuan | Li, Jianzhong | Wang, Huili
Prothioconazole (PTC) is a widely used triazolinthione fungicide with low toxicity and short residual period. However, its desulfurization metabolite, prothioconazole-desthio (PTC-d), is more persistent and has higher toxicity in terrestrial animals. In this study, the toxicokinetics (TK) and tissue distribution of PTC and PTC-d in Chinese lizards (Eremias argus) were measured following single oral dose (100 mg kg⁻¹ body weight) treatments. TK parameters indicated that PTC was more rapidly absorbed than PTC-d, as indicated by its shorter time to reach peak concentrations in most tissues. Furthermore, the relative bioavailability of PTC in lizards was lower than that of PTC-d. Compared with PTC, PTC-d preferentially accumulated in lizards, as reflected by longer half-life of PTC-d. During the distribution process, PTC-d generated in vivo was transported from other tissues and was deposited in the skin and tail, where PTC-d may be excreted by exuviation or tail detachment. Preferential enrichment of S-enantiomer of both PTC and PTC-d were observed in all tissues. Hepatic cytochrome P450 gene expression measurement revealed that cyp1a5 and cyp3a28 exhibited the strongest responses in both treatment groups. In addition, the opposite responses of cyp2k4 in different treatment groups may indicate that this enzyme caused differences in the rates of metabolism of the two chemicals. This study compared the TK profile of PTC and its desulfurization metabolite PTC-d in lizards and demonstrated that the desulfurization of PTC could increase its ecological risk due to the higher bioavailability and persistence of PTC-d.
اظهر المزيد [+] اقل [-]Dibutyl phthalate exposure disrupts the progression of meiotic prophase I by interfering with homologous recombination in fetal mouse oocytes
2019
Tu, Zhihan | Mu, Xinyi | Chen, Xuemei | Geng, Yanqing | Zhang, Yan | Li, Qingying | Gao, Rufei | Liu, Taihang | Wang, Yingxiong | He, Junlin
Dibutyl phthalate (DBP), one of the most widely used plasticizers, is a known environmental endocrine disruptor that impairs male and female fertility. In this study, oral administration of DBP was given to pregnant mice on 14.5 days post coitus (dpc) for 3 days; and additionally, DBP was added into the culture of 14.5 dpc fetal ovaries for 3 days. DBP exposure during gestation disturbed the progression of meiotic prophase I of mouse oocytes, specifically from the zygotene to pachytene stages. Meanwhile, the DBP-exposed pachytene oocytes showed increased homologous recombination sites and unrepaired DNA damage. Furthermore, DBP caused DNA damage by increasing oxidative stress, decreased the expression of multiple critical meiotic regulators, and consequently induced oocyte apoptosis. Moreover, the effect of DBP on meiosis I prophase involved estrogen receptors α and β. Collectively, these results demonstrated a set of meiotic defects in DBP-exposed fetal oocytes. As aberrations in homologous recombination can result in aneuploid gametes and embryos, this study provides new support for the deleterious effects of phthalates.
اظهر المزيد [+] اقل [-]Early-life exposure to bisphenol A induces dysregulation of lipid homeostasis by the upregulation of SCD1 in male mice
2022
Fang, Ruyue | Yang, Shaohua | Gu, Xiaozhen | Li, Changqing | Bi, Nanxi | Wang, Hui-Li
Exposure of Bisphenol A (BPA) is closely associated with an increased prevalence of obesity-related metabolic syndrome. However, the potential mechanism of BPA-induced adipogenesis remains to be fully elucidated. Herein, potential mechanisms of BPA-induced adipogenesis in 3T3-L1 preadipocytes were evaluated using RNA-Seq. Then, using an early-life BPA exposure model, we further evaluated the effects of BPA exposure on lipid and glucose homeostasis. The results showed that lipid content in 3T3-L1 adipocytes was significantly increased after BPA exposure (p < 0.01) and male C57BL/6 mice with the dose of 500 μg/kg/day BPA by once-a-day oral administration for 8 weeks displayed a NAFLD-like phenotype. RNA-Seq analysis of preadipocytes showed that BPA exposure affected multiple biological processes including glycosphingolipid biosynthesis, regulation of lipolysis in adipocytes, PPAR signaling pathway and fatty acid metabolism. The dysregulation in a series of genes of mice was associated to de novo lipogenesis and lipid transport, which was linked to obesity. Importantly, we also found a significant expression increase of stearoyl-CoA desaturase 1 (SCD1) and a significant decrease of apolipoprotein D (APOD) in both fat (p < 0.01) and livers (p < 0.01) of male mice. Besides, the dysregulation of pro-inflammatory genes (TNF-α,IL-6 and SAA3) showed that BPA exposure promoted progression of hepatic inflammation. In conclusion, this study elucidated a novel mechanism in which obesity associated with BPA exposure by targeting SCD1. Exposure to BPA should be carefully examined in the chronic liver metabolic diseases.
اظهر المزيد [+] اقل [-]Results of a 30-day safety assessment in young mice orally exposed to polystyrene nanoparticles
2022
Xiao, Junting | Jiang, Xuejun | Zhou, Yujian | Sumayyah, Golamaully | Zhou, Lixiao | Tu, Baijie | Qin, Qizhong | Qiu, Jingfu | Qin, Xia | Zou, Zhen | Chen, Chengzhi
Polystyrene nanoparticles (PSNPs) are a newly emerging pollutant in the natural environment. However, due to the lack of sufficient toxicological studies in mammals, the potential effects of PSNPs on human health remain largely undefined. Therefore, in this study, young mice aged four weeks old were subjected to oral administration of 0, 0.2, 1, or 10 mg/kg PSNPs for 30 days. Our results demonstrated for the first time that oral exposure to PSNPs affected the expressions of mucus secretion-related genes and altered the community composition of intestinal microbiota, although this treatment did not cause behavioral impairments in young mice. No significant alterations in inflammatory or oxidative stress-related indicators were observed in the liver, lung, intestine, cortex or serum of PSNPs-treated animals. Moreover, exposure to PSNPs did not cause pathological changes in the liver, lung, or cortex tissues. Notably, although oral administration of PSNPs did not produce obvious toxic effects in the major organs of young mice, the possible toxicity of PSNPs remains unresolved and it may depend on the dose, exposure route and species. The potential hazardous effects of PSNPs still need to be systematically assessed, especially for children who are susceptible to exposure to nanoparticles.
اظهر المزيد [+] اقل [-]Polystyrene microplastics cause cardiac fibrosis by activating Wnt/β-catenin signaling pathway and promoting cardiomyocyte apoptosis in rats
2020
Li, Zekang | Zhu, Shuxiang | Liu, Qian | Wei, Jialiu | Jin, Yinchuan | Wang, Xifeng | Zhang, Lianshuang
Microplastics (MPs) are new persistent organic pollutants derived from the degradation of plastics. They can accumulate along the food chain and enter the human body through oral administration, inhalation and dermal exposure. To identify the impact of Polystyrene (PS) MPs on the cardiovascular system and the underlying toxicological mechanism, 32 male Wister rats were divided into control group and three model groups, which were exposed to 0.5 μm PS MPs at 0.5, 5 and 50 mg/L for 90 days. Our results suggested that PS MPs exposure increased Troponin I and creatine kinase-MB (CK-MB) levels in serum, resulted in structure damage and apoptosis of myocardium, and led to collagen proliferation of heart. Moreover, PS MPs could induce oxidative stress and thus activate fibrosis-related Wnt/β-catenin signaling pathway. These results suggested that PS MPs could lead to cardiovascular toxicity by inducing cardiac fibrosis via activating Wnt/β-catenin pathway and myocardium apoptosis triggered by oxidative stress. The present study provided some novelty evidence to elucidate the potential mechanism of cardiovascular toxicity induced by PS MPs.
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