ENVIRONMENTAL POLLUTION
·
2025
·
IF 7.3
Minyi Huang,Wentao Huang,Renyan Duan,Yingfeng Huang,Yongqiang Xia
Baicalein has pharmacological functions, such as antioxidant and anti-inflammatory properties, and has been shown to alleviate damage to organs caused by environmental pollutants. However, the mechanism by which baicalein reduces the toxic effects of metals needs further research. This study used Pelophylax nigromaculatus tadpoles as a model to explore the toxicological effects of lead (Pb) on the gut-liver axis, and the mechanism by which baicalein alleviates lead toxicity. Analysis of the gut microbiota showed that baicalein alleviated abnormal changes in the gut microbiota following Pb exposure, mainly by increasing the abundance of beneficial bacterial genera, including Cetobacterium , Clostridioides , and Monoglobus . Liver metabolomics showed that compared to a natural recovery, baicalein treatment significantly increased the content of metabolites such as uridine, 17α-hydroxypregnenolone, niacin, and cucurbitacin E, and significantly reduced the content of metabolites such as linoleic, gluconic acid, and tetrahydrocortisone. These differential metabolites could be enriched in pathways such as pyrimidine metabolism, nicotinic acid and nicotinamide metabolism, and steroid hormone biosynthesis, which were beneficial for the treatment of liver injury. There was a significant correlation between the gut microbiota and the main differential metabolites in the liver with the addition of baicalein. The improvement of these metabolic pathways by baicalein is beneficial for the repair of the liver and intestines. Therefore, baicalein can increase the abundance of beneficial gut microbiota, improve liver metabolism, and thus reduce the damage of Pb exposure to the gut-liver axis.
研究领域:
环境毒理学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Microbiology
·
2018
·
IF 4.019
Muhammad Zafarullah,Ramzan Rabia,Zhang Shanshan,Hu Haijuan,Hameed Ahsan,Bakry Amr M.,Dong Yongzhen,Wang Lufeng,Pan Siyi
Lead (Pb) is a well-recognized and potent heavy metal with non-biodegradable nature and can induce the oxidative stress, degenerative damages in tissues, and neural disorders. Certain lactic acid bacterial strains retain the potential to mitigate the lethal effects of Pb. The present work was carried out to assess the Pb bio-sorption and tolerance capabilities of Lactobacillus plantarum spp. Furthermore, potato resistant starch (PRS)-based microencapsulated and non-encapsulated L. plantarum KLDS 1.0344 was utilized for bioremediation against induced chronic Pb toxicity in mice. The experimental mice were divided into two main groups (Pb exposed and non-Pb exposed) and, each group was subsequently divided into three sub groups. The Pb exposed group was exposed to 100 mg/L Pb(NO3)2 via drinking water, and non-Pb exposed group was supplied with plain drinking water during 7 weeks prolonged in vivo study. The accumulation of Pb in blood, feces, renal, and hepatic tissues and its pathological damages were analyzed. The effect of Pb toxicity on the antioxidant enzyme capabilities in blood, serum, as well as, on levels of essential elements in tissues was also calculated. Moreover, KLDS 1.0344 displayed remarkable Pb binding capacity 72.34% and Pb tolerance (680 mg/L). Oral administration of both non- and PRS- encapsulated KLDS 1.0344 significantly provided protection against induced chronic Pb toxicity by increasing fecal Pb levels (445.65 ± 22.28 μg/g) and decreasing Pb in the blood up to 137.63 ± 2.43 μg/L, respectively. KLDS 1.0344 microencapsulated with PRS also relieved the renal and hepatic pathological damages and improved the antioxidant index by inhibiting changes in concentrations of glutathione peroxidase, glutathione, superoxide dismutase, malondialdehyde, and activated oxygen species, which were affected by the Pb exposure. Overall, our results suggested that L. plantarum KLDS 1.0344 either in free or encapsulated forms hold the potentiality to deliver a dietetic stratagem against Pb lethality.
研究领域:
环境生物学
·
微生物学
·
毒理学
✓ 已验证
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2024
·
IF 3.9
Yiren Xiong,Jiayi He,Shanshan He,Zuqing Hu,Di Ouyang,Renyi Liu,Zhenjie Gao,Weiguang Zhang,Zhujun Kang,Shuyi Lan,Yang Wang,Fatoumata Diallo,Dalin Hu
Lead is a ubiquitous environmental chemical with various toxic damage to human body. This investigation aimed to explore the intervention effect of human umbilical cord mesenchymal stem cells derived exosomes (HUC-MSC-exo) on the neurotoxicity of lead and the relevant mechanism. Differential gradient ultracentrifugation was adopted to isolate HUC-MSC-exo. Nanoparticle tracking assay (NTA), Transmission electron microscope (TEM) technology and exosomal specific biomarkers CD9, CD63 and CD81 were adopted for exosomal characterization. Human neuroblastoma cell (SH-SY5Y) was used as the recipient cell. Confocal laser scanning microscope analysis was conducted to confirm the intake of HUC-MSC-exo by SH-SY5Y cells. Cell migration ability, apoptosis, IL-6, IL-1β and TNF-α were analyzed. The role of miR-26a-5p/PTEN axis was assessed. The result showed that the exposure of SH-SY5Y cells to lead activated the miR-26a-5p/PTEN pathway by down-regulating miR-26a-5p and up-regulating PTEN expression, which was related to the significantly decreased cell migration and increased apoptosis, as well as significantly enhanced levels of inflammatory cytokine as compared with the control. While HUC-MSC-exo could significantly alleviate the cytotoxicity, apoptosis and inflammatory effects induced by lead on SH-SY5Y cells via partially restoring miR-26a-5p/PTEN pathway. Herein, we conclude that HUC-MSC-exo can alleviate lead-induced toxic effects on SH-SY5Y cells partially through miR-26a-5p/PTEN pathway.
研究领域:
毒理学
·
干细胞研究
·
神经科学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2024
·
IF 6.2
Yiren Xiong,Zuqing Hu,Di Ouyang,Meilin Tang,Jiayi He,Shanshan He,Renyi Liu,Zhenjie Gao,Ying Chen,Dalin Hu
Lead is a widespread environmental pollutant with serious adverse effects on human health, but the mechanism underlying its toxicity remains elusive. This study aimed to investigate the role of miR-584–5p / Ykt6 axis in the toxic effect of lead on HK-2 cells and the related mechanism. Our data suggested that lead exposure caused significant cytotoxicity, DNA and chromosome damage to HK-2 cells. Mechanistically, lead exposure down-regulated miR-584–5p and up-regulated Ykt6 expression, consequently, autophagosomal number and autophagic flux increased, lysosomal number and activity decreased, exosomal secretion increased. Interestingly, when miR-584–5p level was enhanced with mimic, autophagosomal number and autophagic flux decreased, lysosomal number and activity increased, ultimately, exosomal secretion was down-regulated, which resulted in significant aggravated toxic effects of lead. Further, directly blocking exosomal secretion with inhibitor GW4869 also resulted in exacerbated toxic effects of lead. Herein, we conclude that miR-584–5p / Ykt6 - mediated autophagy - lysosome - exosome pathway may be a critical route affecting the toxic effects of lead on HK-2 cells. We provide a novel insight into the mechanism underlying the toxicity of lead on human cells.
研究领域:
毒理学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2025
·
IF 6.1
Jiayi He,Zuqing Hu,Zhenjie Gao,Renyi Liu,Zhujun Kang,Shuyi Lan,Yang Wang,Shanshan He,Hongyi Xian,Fatoumata Diallo,Yunxia Jiang,Jiguo Wu,Suli Huang,Ziquan Lv,Dalin Hu
Lead is an important heavy metal material and also an omnipresent environmental pollutant, which poses extensive hazards to human health, including its nephrotoxicity. However, there are still many unknowns regarding its toxic mechanism and intervention strategy. Here, we revealed that lead exposure promoted the activation of PERK in HK - 2 cells (p - PERK and the ratio of p - PERK / PERK increased), enhanced the expression of its molecular chaperone binding immunoglobulin protein (BIP) and its downstream signaling molecule CCAAT / enhancer - binding protein homologous protein (CHOP). This indicated that lead exposure resulted in the occurrence of the unfolded protein response (UPR) in HK - 2 cells. Further, lead induced significant DNA damage, oxidative stress and apoptosis in HK-2 cells. Especially, when human umbilical cord mesenchymal stem cell - derived exosomes (hucMSC - exos) were ingested by HK-2 cells, all the levels of p - PERK, p - PERK / PERK ratio, BIP and CHOP were significantly down - regulated, which suggested that the UPR was significantly alleviated. Simultaneously, the above-mentioned toxic effects of lead were significantly reduced. Moreover, when GSK2606414 was employed to block the phosphorylation of PERK, the toxic effects of lead were also significantly alleviated. Hence, we conclude that hucMSC - exos can alleviate the toxicity of lead to HK-2 cells via interfering with the UPR, in which PERK plays a crucial role, and it may be a promising target for intervening in the toxicity of lead.
研究领域:
毒理学
·
细胞生物学
·
环境卫生
·
干细胞研究
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY
·
2021
·Vol. 30
·期 5
·885-898
·
IF 2.823
Liu Haisu,Zhang Sanshan,Qiu Ming,Wang Anli,Ye Jianmin,Fu Shengli
The heavy metal lead (Pb) is a contaminant widely distributed in the food chain. In this study, eight weeks of feeding containing Garlic ( Allium sativum ) or Fu-ling ( Poria cocos ) or both, markedly increased the growth index, enzyme activity, and serum index and significantly decreased muscle Pb level in grass carp ( Ctenopharyngodon idella ). Upon Pb exposure, the feeding Garlic or Fu-ling or both possessed the similar effects on improving the function of the antioxidant system and chelating ability. Further, the gene expressions of metal binding proteins ( TF and MT-2 ) in the liver of the three experimental groups were significantly higher than those of the control group, which were all highly up-regulated after Pb exposure. At the same time, the activities of antioxidant enzymes (SOD and CAT) and the content of non-enzymatic substance (GSH) in the liver of the Garlic group, Fu-ling group and mixed group were stable compared to the control group after Pb exposure. Moreover, the reduction of Pb toxicity was manifested by the decrease of Pb content in the muscle, and the stable expression of heat stress proteins ( HSP30 and HSP60 ) and immune-related genes ( TNF-α and IL-1β ). Taken together, the study preliminarily shows that the Garlic and Fu-ling play a role in mitigating the toxicity of Pb in grass carp.
研究领域:
水产养殖
·
毒理学
·
环境科学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）