Iodoacetic acid(IAA) is an unregulated water disinfection byproduct that is an ovarian toxicant. However, the mechanisms of action underlying IAA toxicity in ovarian follicles remain unclear. Thus, we determined wheth...Iodoacetic acid(IAA) is an unregulated water disinfection byproduct that is an ovarian toxicant. However, the mechanisms of action underlying IAA toxicity in ovarian follicles remain unclear. Thus, we determined whether IAA alters gene expression in ovarian follicles in mice. Adult female mice were dosed with water or IAA(10 or 500 mg/L) in the water for 35-40 days. Antral follicles were collected for RNA-sequencing analysis and sera were collected to measure estradiol. RNA-sequencing analysis identified 1063 differentially expressed genes(DEGs) in the 10 and 500 mg/L IAA groups(false discovery rate FDR < 0.1), respectively, compared to controls. Gene Ontology Enrichment analysis showed that DEGs were involved with RNA processing and regulation of angiogenesis(10 mg/L) and the cell cycle and cell division(500 mg/L). Pathway Enrichment analysis showed that DEGs were involved in the phosphatidylinositol 3-kinase and protein kinase B(PI3K-Akt), gonadotropin-releasing hormone(Gn RH), estrogen, and insulin signaling pathways(10 mg/L). Pathway Enrichment analysis showed that DEGs were involved in the oocyte meiosis, Gn RH, and oxytocin signaling pathways(500 mg/L). RNA-sequencing analysis identified 809 DEGs when comparing the 500 and 10 mg/L IAA groups(FDR < 0.1). DEGs were related to ribosome, translation, m RNA processing, oxidative phosphorylation, chromosome, cell cycle, cell division, protein folding, and the oxytocin signaling pathway. Moreover, IAA exposure significantly decreased estradiol levels(500 mg/L) compared to control. This study identified key candidate genes and pathways involved in IAA toxicity and can help to further understand the molecular mechanisms of IAA toxicity in ovarian follicles.展开更多
Iodoacetic acid(IAA) is an unregulated disinfection byproduct in drinking water and has been shown to exert cytotoxicity, genotoxicity, tumorigenicity, and reproductive and developmental toxicity. However, the effects...Iodoacetic acid(IAA) is an unregulated disinfection byproduct in drinking water and has been shown to exert cytotoxicity, genotoxicity, tumorigenicity, and reproductive and developmental toxicity. However, the effects of IAA on gut microbiota and its metabolism are still unknown, especially the association between gut microbiota and the metabolism and toxicity of IAA. In this study, female and male Sprague–Dawley rats were exposed to IAA at 0 and 16 mg/kg bw/day daily for 8 weeks by oral gavage. Results of 16S r RNA gene sequencing showed that IAA could alter the diversity, relative abundance and function of gut microbiota in female and male rats. IAA also increased the abundance of genes related to steroid hormone biosynthesis in the gut microbiota of male rats. Moreover, metabolomics profiling revealed that IAA could significantly disturb 6 and 13 metabolites in the feces of female and male rats, respectively. In female rats, the level of androstanediol increased in the IAA treatment group. These results were consistent with our previous findings, where IAA was identified as an androgen disruptor. Additionally, the perturbed gut microbiota and altered metabolites were correlated with each other. The results of this study indicated that IAA could disturb gut microbiota and its metabolism. These changes in gut microbiota and its metabolism were associated with the reproductive and developmental toxicity of IAA.展开更多
Iodoacetic acid(IAA) has been applied to different species to acutely induce photoreceptor degeneration.The purpose of the present study was to use this toxin to thoroughly eliminate photoreceptors and induce complete...Iodoacetic acid(IAA) has been applied to different species to acutely induce photoreceptor degeneration.The purpose of the present study was to use this toxin to thoroughly eliminate photoreceptors and induce complete blindness in the cat.IAA was delivered by single ear vein injection(20 mgkg-1).Six months after the IAA treatment,functional evaluations including pupillary light reflex(PLR),electroretinogram(ERG),visual behavior tests were performed.Morphological examinations were carried out after the functional evaluation.The present result shows that,six months after the IAA application,animals lost visual functions and became completely blind.High dose IAA application via ear vein delivery created an acute and reliable complete photoreceptor degeneration model in the cat.This model can be applied to genetic and cellular therapies for visual function restoration.展开更多
Objective: To observe the effect of intraplantar injection of monosodium iodoacetate (MIA) on pain perception in rats and to investigate the role of transient receptor potential vanilloid type 1 (TRPV1) in the effect....Objective: To observe the effect of intraplantar injection of monosodium iodoacetate (MIA) on pain perception in rats and to investigate the role of transient receptor potential vanilloid type 1 (TRPV1) in the effect. Methods: Adult male Wistar rats were used in the experiment. 1) MIA was injected subcutaneously into the right hindpaw of rats, the low, medium, and high doses of MIA were 0.11, 0.33, and 1 mg, respectively, then the changes of paw withdrawal thermal latency, paw withdrawal mechanical threshold, and dynamic weight bearing within 4 hours after MIA injection were measured. 2) Capsazepine (TRPV1 antagonist, 30 μg) was injected subcutaneously into the right hindpaw of rats at 2 hours after intraplantar injection of MIA (1 mg), then the changes of paw withdrawal thermal latency, paw withdrawal mechanical threshold, and dynamic weight bearing within 1 hour after capsazepine injection were measured. Results: 1) The paw withdrawal thermal latency, paw withdrawal mechanical threshold, and dynamic weight bearing decreased after intraplantar injection of MIA in rats and the effect lasted for at least 4 hours. 2) The MIA-induced reduction in paw withdrawal thermal latency, paw withdrawal mechanical threshold, and dynamic weight bearing were significantly alleviated after intraplantar injection of capsazepine in rats. Conclusion: Intraplantar injection of MIA can produce thermal pain, mechanical pain, and spontaneous pain for more than 4 hours, which may be due to the TRPV1 activation caused by MIA.展开更多
A survey was conducted at eight U.S. drinking water plants, that spanned a wide range of water qualities and treatment/disinfection practices. Plants that treated heavily-wastewaterimpacted source waters had lower tri...A survey was conducted at eight U.S. drinking water plants, that spanned a wide range of water qualities and treatment/disinfection practices. Plants that treated heavily-wastewaterimpacted source waters had lower trihalomethane to dihaloacetonitrile ratios due to the presence of more organic nitrogen and HAN precursors. As the bromide to total organic carbon ratio increased, there was more bromine incorporation into DBPs. This has been shown in other studies for THMs and selected emerging DBPs(HANs), whereas this study examined bromine incorporation for a wider group of emerging DBPs(haloacetaldehydes, halonitromethanes). Moreover, bromine incorporation into the emerging DBPs was, in general, similar to that of the THMs. Epidemiology studies that show an association between adverse health effects and brominated THMs may be due to the formation of brominated emerging DBPs of heath concern. Plants with higher free chlorine contact times before ammonia addition to form chloramines had less iodinated DBP formation in chloraminated distribution systems, where there was more oxidation of the iodide to iodate(a sink for the iodide) by the chlorine. This has been shown in many bench-scale studies(primarily for iodinated THMs), but seldom in full-scale studies(where this study also showed the impact on total organic iodine. Collectively, the THMs, haloacetic acids, and emerging DBPs accounted for a significant portion of the TOCl, TOBr, and TOI;however, ~50% of the TOCl and TOBr is still unknown. The correlation of the sum of detected DBPs with the TOCl and TOBr suggests that they can be used as reliable surrogates.展开更多
Background: Novel preclinical models for prediction of osteoarthritis-like pain are necessary for the elucidation of osteoarthritis (OA) pathology and for assessment of novel analgesics. A widely used behavioral test ...Background: Novel preclinical models for prediction of osteoarthritis-like pain are necessary for the elucidation of osteoarthritis (OA) pathology and for assessment of novel analgesics. A widely used behavioral test in rat models of tibiofemoral OA is hind limb weight bearing (WB). However, this method evaluates WB in an unnaturally restricted manner. The aim of this study was therefore to characterize the Tekscan Pressure Measurement System as a means to assess OA-like tibiofemoral pain in rats by determination of plantar pressure distribution in a more natural and unrestricted position, defined as unrestricted WB. Methods: Intra-articular injections of 1 mg monosodium iodoacetate (MIA) or saline were administrated in the left hind knee of 84 male Sprague Dawley rats. Changes in unrestricted WB between ipsilateral and contralateral hindlimbs were determined. Morphine (5 mg/kg administered subcutaneously) and naproxen (60 mg/kg per-oral) were examined for their ability to reverse WB changes. Results: Changes in hind limb unrestricted WB were observed 14 (P P P Conclusion: This study indicated that unrestricted WB assessed by the Tekscan system can be utilized as a clinically relevant method to assess aberrations in WB induced by intra-articular MIA injections in rodents. Therefore, this system may be useful for understanding the mechanisms of OA pain in humans and may also assist in the discovery of novel pharmacological agents.展开更多
基金supported by grant numbers NIH R21 ES028963 , NIH T32 ES007326an Environmental Toxicology Fellowship。
文摘Iodoacetic acid(IAA) is an unregulated water disinfection byproduct that is an ovarian toxicant. However, the mechanisms of action underlying IAA toxicity in ovarian follicles remain unclear. Thus, we determined whether IAA alters gene expression in ovarian follicles in mice. Adult female mice were dosed with water or IAA(10 or 500 mg/L) in the water for 35-40 days. Antral follicles were collected for RNA-sequencing analysis and sera were collected to measure estradiol. RNA-sequencing analysis identified 1063 differentially expressed genes(DEGs) in the 10 and 500 mg/L IAA groups(false discovery rate FDR < 0.1), respectively, compared to controls. Gene Ontology Enrichment analysis showed that DEGs were involved with RNA processing and regulation of angiogenesis(10 mg/L) and the cell cycle and cell division(500 mg/L). Pathway Enrichment analysis showed that DEGs were involved in the phosphatidylinositol 3-kinase and protein kinase B(PI3K-Akt), gonadotropin-releasing hormone(Gn RH), estrogen, and insulin signaling pathways(10 mg/L). Pathway Enrichment analysis showed that DEGs were involved in the oocyte meiosis, Gn RH, and oxytocin signaling pathways(500 mg/L). RNA-sequencing analysis identified 809 DEGs when comparing the 500 and 10 mg/L IAA groups(FDR < 0.1). DEGs were related to ribosome, translation, m RNA processing, oxidative phosphorylation, chromosome, cell cycle, cell division, protein folding, and the oxytocin signaling pathway. Moreover, IAA exposure significantly decreased estradiol levels(500 mg/L) compared to control. This study identified key candidate genes and pathways involved in IAA toxicity and can help to further understand the molecular mechanisms of IAA toxicity in ovarian follicles.
基金supported by the National Natural Science Foundation of China (Nos. 82160603 , 81560524 , 81360421)the Guangxi Natural Science Foundation (No. 2018GXNSFAA050076)Innovation Project of Guangxi Graduate Education (No. YCSW2020123)。
文摘Iodoacetic acid(IAA) is an unregulated disinfection byproduct in drinking water and has been shown to exert cytotoxicity, genotoxicity, tumorigenicity, and reproductive and developmental toxicity. However, the effects of IAA on gut microbiota and its metabolism are still unknown, especially the association between gut microbiota and the metabolism and toxicity of IAA. In this study, female and male Sprague–Dawley rats were exposed to IAA at 0 and 16 mg/kg bw/day daily for 8 weeks by oral gavage. Results of 16S r RNA gene sequencing showed that IAA could alter the diversity, relative abundance and function of gut microbiota in female and male rats. IAA also increased the abundance of genes related to steroid hormone biosynthesis in the gut microbiota of male rats. Moreover, metabolomics profiling revealed that IAA could significantly disturb 6 and 13 metabolites in the feces of female and male rats, respectively. In female rats, the level of androstanediol increased in the IAA treatment group. These results were consistent with our previous findings, where IAA was identified as an androgen disruptor. Additionally, the perturbed gut microbiota and altered metabolites were correlated with each other. The results of this study indicated that IAA could disturb gut microbiota and its metabolism. These changes in gut microbiota and its metabolism were associated with the reproductive and developmental toxicity of IAA.
基金supported by National Basic Research Program of China(2009CB320900 and 2011CB510206 to Pu MingLiang,2011CB510200to Li XiaoXin)National Natural Science Foundation of China(30831160516 to Pu MingLiang)
文摘Iodoacetic acid(IAA) has been applied to different species to acutely induce photoreceptor degeneration.The purpose of the present study was to use this toxin to thoroughly eliminate photoreceptors and induce complete blindness in the cat.IAA was delivered by single ear vein injection(20 mgkg-1).Six months after the IAA treatment,functional evaluations including pupillary light reflex(PLR),electroretinogram(ERG),visual behavior tests were performed.Morphological examinations were carried out after the functional evaluation.The present result shows that,six months after the IAA application,animals lost visual functions and became completely blind.High dose IAA application via ear vein delivery created an acute and reliable complete photoreceptor degeneration model in the cat.This model can be applied to genetic and cellular therapies for visual function restoration.
文摘Objective: To observe the effect of intraplantar injection of monosodium iodoacetate (MIA) on pain perception in rats and to investigate the role of transient receptor potential vanilloid type 1 (TRPV1) in the effect. Methods: Adult male Wistar rats were used in the experiment. 1) MIA was injected subcutaneously into the right hindpaw of rats, the low, medium, and high doses of MIA were 0.11, 0.33, and 1 mg, respectively, then the changes of paw withdrawal thermal latency, paw withdrawal mechanical threshold, and dynamic weight bearing within 4 hours after MIA injection were measured. 2) Capsazepine (TRPV1 antagonist, 30 μg) was injected subcutaneously into the right hindpaw of rats at 2 hours after intraplantar injection of MIA (1 mg), then the changes of paw withdrawal thermal latency, paw withdrawal mechanical threshold, and dynamic weight bearing within 1 hour after capsazepine injection were measured. Results: 1) The paw withdrawal thermal latency, paw withdrawal mechanical threshold, and dynamic weight bearing decreased after intraplantar injection of MIA in rats and the effect lasted for at least 4 hours. 2) The MIA-induced reduction in paw withdrawal thermal latency, paw withdrawal mechanical threshold, and dynamic weight bearing were significantly alleviated after intraplantar injection of capsazepine in rats. Conclusion: Intraplantar injection of MIA can produce thermal pain, mechanical pain, and spontaneous pain for more than 4 hours, which may be due to the TRPV1 activation caused by MIA.
基金funding from the National Science Foundation (CBET 1705206 and 1706862)。
文摘A survey was conducted at eight U.S. drinking water plants, that spanned a wide range of water qualities and treatment/disinfection practices. Plants that treated heavily-wastewaterimpacted source waters had lower trihalomethane to dihaloacetonitrile ratios due to the presence of more organic nitrogen and HAN precursors. As the bromide to total organic carbon ratio increased, there was more bromine incorporation into DBPs. This has been shown in other studies for THMs and selected emerging DBPs(HANs), whereas this study examined bromine incorporation for a wider group of emerging DBPs(haloacetaldehydes, halonitromethanes). Moreover, bromine incorporation into the emerging DBPs was, in general, similar to that of the THMs. Epidemiology studies that show an association between adverse health effects and brominated THMs may be due to the formation of brominated emerging DBPs of heath concern. Plants with higher free chlorine contact times before ammonia addition to form chloramines had less iodinated DBP formation in chloraminated distribution systems, where there was more oxidation of the iodide to iodate(a sink for the iodide) by the chlorine. This has been shown in many bench-scale studies(primarily for iodinated THMs), but seldom in full-scale studies(where this study also showed the impact on total organic iodine. Collectively, the THMs, haloacetic acids, and emerging DBPs accounted for a significant portion of the TOCl, TOBr, and TOI;however, ~50% of the TOCl and TOBr is still unknown. The correlation of the sum of detected DBPs with the TOCl and TOBr suggests that they can be used as reliable surrogates.
文摘Background: Novel preclinical models for prediction of osteoarthritis-like pain are necessary for the elucidation of osteoarthritis (OA) pathology and for assessment of novel analgesics. A widely used behavioral test in rat models of tibiofemoral OA is hind limb weight bearing (WB). However, this method evaluates WB in an unnaturally restricted manner. The aim of this study was therefore to characterize the Tekscan Pressure Measurement System as a means to assess OA-like tibiofemoral pain in rats by determination of plantar pressure distribution in a more natural and unrestricted position, defined as unrestricted WB. Methods: Intra-articular injections of 1 mg monosodium iodoacetate (MIA) or saline were administrated in the left hind knee of 84 male Sprague Dawley rats. Changes in unrestricted WB between ipsilateral and contralateral hindlimbs were determined. Morphine (5 mg/kg administered subcutaneously) and naproxen (60 mg/kg per-oral) were examined for their ability to reverse WB changes. Results: Changes in hind limb unrestricted WB were observed 14 (P P P Conclusion: This study indicated that unrestricted WB assessed by the Tekscan system can be utilized as a clinically relevant method to assess aberrations in WB induced by intra-articular MIA injections in rodents. Therefore, this system may be useful for understanding the mechanisms of OA pain in humans and may also assist in the discovery of novel pharmacological agents.
