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Outline
To investigate whether trichlorfon exposure induces hepatic injury and lipid accumulation by downregulating IRX5 expression.
Male SD rats were randomly divided into control, low-dose (10 mg/kg), and high-dose (25 mg/kg) trichlorfon gavage groups and exposed for 30 days. Serum liver function (ALT, AST) and blood lipids (TG, TC) were detected; liver histopathology and hepatocyte apoptosis were observed by H&E and TUNEL staining; RT-qPCR and Western Blot were used to detect the expression of inflammation, apoptosis, lipid metabolism-related genes, and IRX5; molecular docking was performed to predict the binding between trichlorfon and IRX5. In vitro experiments were conducted using HepG2 cells as a model, with 200 μM determined as the subtoxic concentration. Cells were divided into control, 200 μM trichlorfon treatment, and 200 μM trichlorfon combined with IRX5 overexpression (OE-IRX5) groups. Intracellular lipid droplets were observed by Oil Red O staining, cell viability was evaluated by CCK-8 assay, and lipid metabolism key proteins were detected by Western Blot.
Compared with the control group, the trichlorfon treatment group showed decreased body weight (P<0.001), significantly increased serum ALT, AST, TG, and TC levels (P<0.000 1); liver tissue exhibited inflammatory damage, increased hepatocyte apoptosis, upregulated lipid metabolism-related gene expression (P<0.001), and downregulated IRX5 expression (P<0.01). Molecular docking showed that the binding energy between trichlorfon and IRX5 was-7.43 kcal/mol. In vitro experiments, 200 μM trichlorfon induced lipid droplet accumulation and downregulated IRX5 (P<0.05); IRX5 overexpression significantly reduced lipid accumulation, partially restored cell viability, and improved lipid metabolism disorder.
Chronic trichlorfon exposure causes hepatic injury and lipid accumulation in rats, potentially through downregulation of IRX5 expression. These findings implicate IRX5 as a critical mediator in trichlorfon-induced hepatotoxicity and metabolic disruption.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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