FOOD AND CHEMICAL TOXICOLOGY
·
2024
·
IF 3.9
Chengping Kang,Qianqian Xiao,Xiaoxia Wang,Wanqian Guo,Haoran Zhang,Lilan Yuan,Zhe Zhao,Weidong Hao
Chlormequat chloride (CCC), a widely used plant growth regulator, is a choline analogue that has been shown to have endocrine-disrupting effects. Previous studies have shown that maternal exposure to CCC could induce hyperlipidemia and growth disruption in rat offspring. This study aims to further investigate the effects of peripubertal exposure to CCC on pubertal development and lipid homeostasis, as well as the underlying mechanisms. In vivo , male weanling rats were exposed to CCC (0, 20, 75 and 200 mg/kg bw/day) from post-natal day 21 to 60 via daily oral gavage. The results in rats showed that 75 mg/kg CCC treatment induced hepatic steatosis, predominantly microvesicular steatosis with a small amount of macrovesicular steatosis, in rat livers and 200 mg/kg CCC treatment induced liver damage including inflammatory infiltration, hepatic sinusoidal dilation and necrosis. In vitro , HepG2 cells were treated with CCC (0, 30, 60, 120, 240 and 480 μg/mL) for 24 h. And the results showed that CCC above 120 μg/mL induced an increase in triglyceride and neutral lipid levels of HepG2 cells. Mechanism exploration revealed that CCC treatment promoted the activation of mTOR/SREBP1 signalling pathway and inhibited activation of AMPK in both in vivo rat livers and in vitro HepG2 cells. Treatment with AMPK activator Acadesine (AICAR) could alleviate the lipid accumulation in HepG2 cells induced by CCC. Collectively, the present results indicate that CCC might induce hepatic steatosis by promoting mTOR/SREBP1 mediated lipogenesis via AMPK inhibition.
研究领域:
药理学
·
毒理学
·
内分泌学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL SCIENCE & TECHNOLOGY
·
2025
·
IF 11.3
Wen Xie,Yajing Zhang,Yu He,Hang Su,Jinni Zhang,Canrong Chen,Peisi Xie,Jing Chen,Zian Lin,Zongwei Cai
Imidacloprid (IMI), a neonicotinoid insecticide extensively applied in agriculture, is among the most frequently detected pesticides in food. However, the long-term impact of chronic dietary exposure to environmentally relevant IMI doses on kidney health has not been fully elucidated, particularly regarding its nephrotoxic mechanisms. To address this gap, chronic exposure to IMI was administered to mice through supplementation of their feed with environmentally relevant doses (approximately 100 and 1000 μg/kg/day) for 24 weeks to investigate its nephrotoxicity and underlying mechanisms. Toxicological analysis revealed that chronic IMI exposure led to renal dysfunction, histopathological alterations, and excessive apoptosis in mice. Mechanistic investigations suggested that IMI might inhibit AMP-activated protein kinase (AMPK) activity through both direct and indirect pathways. Direct inhibition occurred through the binding of IMI and its metabolites to AMPK, reducing its phosphorylation activity. Indirect inhibition involved excessive production of reactive oxygen species, which suppressed AMPK phosphorylation, leading to sustained purine metabolism dysregulation in the renal system. Consequently, the kidneys showed an aggravated redox imbalance, heightened inflammatory states, and increased cellular apoptosis. The results of this study are intended to raise awareness of pesticide use and food safety among agricultural workers and consumers.
研究领域:
毒理学
·
环境科学
·
生物化学
·
药理学
·
食品安全
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Rui Lv,Houkang Cao,Mingli Zhong,Jianzhao Wu,Shiyuan Lin,Bo Li,Dongyu Chen,Zhiyuan Zhang,Kefeng Zhang,Ya Gao
Alcoholic fatty liver disease (AFLD) is characterized by excessive lipid accumulation in the liver. This study aimed to investigate the protective effects and mechanisms of Polygala fallax Hemsl polysaccharides (PFPs) on AFLD. PFPs were purified and structurally characterized. An AFLD model was established in mice using alcohol and a high-fat diet. A significant reduction in hepatic steatosis was observed following PFPs treatment, evidenced by decreased fat deposition in liver tissues. Additionally, PFPs reduced various liver injury markers, increased levels of antioxidant enzymes, and improved significantly liver function. RNA sequencing revealed that PFPs improved lipid and CYP450 metabolic pathway abnormalities in AFLD mice. Furthermore, PFPs activated the AMPK pathway, reducing lipid accumulation and enhancing lipid metabolism. A HepG2 cell model treated with ethanol and oleic acid showed significant biochemical improvements with PFPs pretreatment, including reduced lipid accumulation and lower reactive oxygen species (ROS) levels. To further elucidate the AMPK and PFPs correlation in AFLD, an AMPK inhibitor (compound C) was used. In vitro and in vivo qRT-PCR and Western blot results confirmed that PFPs protected against AFLD by activating AMPK phosphorylation, regulating lipid synthesis, and inhibiting lipid accumulation. PFPs also modulated CYP2E1 and oxidative stress-related gene expression, affecting liver metabolism.
研究领域:
药理学
·
肝病学
·
分子生物学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELL BIOCHEMISTRY AND BIOPHYSICS
·
2024
·
IF 1.8
Tu Jia,Liu Qiaoling,Sun Huirong,Gan Luzhen
Diabetic cardiomyopathy (DCM) is a prevalent complication of diabetes mellitus characterized by cardiac dysfunction and myocardial remodeling. Farrerol (FA), an active ingredient in Rhododendron with various pharmacological activities, has an unclear specific role in DCM. Therefore, this study aims to investigate the effects of FA on DCM rats and elucidate its mechanism. The type 2 diabetes mellitus (T2DM) model was induced in adult male Sprague-Dawley rats by administering a high-fat diet for 8 weeks along with STZ injection. Subsequent to successful modeling, FA and the positive drug Dapagliflozin (Dapa) were orally administered via gavage for an additional 8-week period. After administration, the rats’ body weight, fasting blood glucose, fasting insulin, and blood lipid profiles were quantified. Cardiac function was assessed through evaluation of cardiac function parameters, histopathological examination and measurement of myocardial enzyme markers were conducted to assess myocardial injury and fibrosis, Oil red O staining was utilized to evaluate myocardial lipid accumulation, wheat germ agglutinin (WGA) staining was used for assessing cardiomyocyte hypertrophy, and Western blot analysis was used to detect the proteins expression level of AMP-activated protein kinase (AMPK) pathway. The rat cardiomyocyte H9c2 were induced with palmitic acid to establish an in vitro cell model of myocardial lipid toxicity. Subsequently, the cells were subjected to treatment with FA and AMPK inhibitor Compound C, followed by assessment of lipid formation and expression levels of proteins related to the AMPK signaling pathway. The findings demonstrated that both FA and Dapa exhibited efficacy in ameliorating diabetic symptoms, cardiac dysfunction, myocardial fibrosis, cardiomyocyte hypertrophy, and lipid accumulation in T2DM rats. Additionally, they were found to enhance AMPK phosphorylation and PPARα expression while down-regulating CD36. Similarly, FA was observed to inhibit lipid formation in H9c2 and activate the AMPK signaling pathway. However, the improved effect of FA on lipotoxic cardiomyocytes induced by palmitic acid was partially reversed by Compound C. Therefore, the activation of the AMPK signaling pathway by FA may enhance cardiac lipid metabolism, thereby improving cardiac dysfunction and myocardial fibrosis in DCM rats.
研究领域:
药理学
·
心脏病学
·
内分泌学
·
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）