Luteolin , a natural flavonoid , can attenuate hepatic lipid accumulation and insulin resistance in obese mice . Therefore, we hypothesized that luteolin may also improve the abnormal glucolipid metabolism of hypertrophic myocardial cells. This study aimed to investigate the effect and possible molecular mechanisms of luteolin. Hypertrophic H9c2 cells were induced by angiotensin II/hypoxia and simultaneously treated with 2 to 8 μg/mL luteolin for 24 h. Luteolin might dose-dependently decrease intracellular total protein, atrial natriuretic peptide , and free fatty acid levels , and increase supernatant glucose levels . Western blot assay showed that luteolin could inhibit the expressions of intracellular hypoxia inducible factor-1α (HIF-1α) and glucose transporter-4 (GLUT-4) proteins, and increase the expressions of intracellular peroxisome proliferator-activated receptor α (PPARα), carnitine palmitoyltransferase-1A (CPT-1A), and pyruvate dehydrogenase kinase-4 (PDK-4) proteins. These findings demonstrate that luteolin can improve abnormal glucolipid metabolism in angiotensin II/hypoxia-induced hypertrophic H9c2 cells, and its mechanisms are related to the inhibition of HIF-1α expression and subsequent modulation of PPARα-mediated target genes, including CPT-1A, PDK-4, and GLUT-4.
The pesticide acetochlor (ACT) is a chiral isomer commonly detected in the global environment, yet its specific impacts on liver function remain poorly understood. We utilized zebrafish and L02 cells as research models to comprehensively investigate how ACT and its chiral isomers affect the liver. Our investigations unveiled that the R , Rac , and S isomers of ACT disrupt hepatic lipid transport, catabolism, and synthesis, leading to delayed yolk sac absorption and the accumulation of lipids in zebrafish embryos. These isomers induce oxidative stress in the liver of zebrafish embryos, reducing antioxidant levels and enzyme activity . The accumulated lipids in the liver render it susceptible to oxidative stress, further exacerbating hepatocyte damage. Hepatocyte damage manifests as extensive vacuolization of liver cells and alterations in liver morphology, which are induced by R , Rac , and S . Furthermore, we elucidated the molecular mechanisms underpinning the disturbance of hepatic lipid metabolism by R , Rac , and S in L02 cells. These compounds stimulate lipid synthesis through the upregulation of the AMPK/SREBP-1c/FAS pathway while inhibiting lipolysis via downregulation of the PPAR-α/CPT-1a pathway. Remarkably, our results highlight that S exhibits significantly higher hepatotoxicity in comparison to R . This study provides valuable insights into the hepatic effects of ACT chiral isomers.
危险品化学品经营许可证（带存储）