Effect of short term exposure to dichlorvos on rat hepatocyte molecularand histopathological approach

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Background: Organophosphate (OP) insecticides are the most widely used in both agricultural and landscape pest control. The mortality and morbidity rate of OP poisoning is high. The aim of the present study is to investigate the effect of acute organophosphate exposure on hepatocyte and to examine caspase 1 and caspase-3 gene expression, and cell apoptosis related genes as p53, Tumor Necrosis Factor-alpha, Hypoxia Inducible Factor 1-alpha expression changes in rat hepatocyte. Material and Methods: 10 adult Wistar Albino female rats weighing 250-300 g were divided into control (n=5) and experiment (n=5) groups. In experimental group, rats were treated 25 mg/kg of dichlorvos (Bayer DDVP EC 550, Bayer) in corn oil by 16 gauge oral gavage tube. In control group, rats were treated only 2.5 ml corn oil by oral gavage. After seven days, all of the rats were sacrificed by cervical dislocation under anesthesia. The liver was removed and divided into fragments. Hepatocyte density and histopathological examination were performed in fixed liver tissues. For this purpose, sections were taken and stained with hematoxylin-eosin. A part of the liver was used for gene expression analysis. Total RNA was extracted from the liver tissue using an RNA isolation reagent via manufacturer's instruction. Changes in mRNA levels, detected using semi-quantitative reverse transcription-polymerase chain reaction, were calculated as the proportion of the target gene amplification products to the amplification products of the housekeeping gene GAPDH. Results: Hepatocyte density were decreased in experimental group compared to control group (p<0.05). The histopathological changes, such as portal inflammation and picnosis were observed in liver sections of experimental group. According to molecular genetics analysis, Caspase 1, Caspase 3, and p53 gene expression were increased in liver tissue after dichlorvos treated rats compared with the control group. There were no expression changes for TNF-Alpha and Hif1-Alpha gene expression level among groups. Conclusion: Acute organophosphate exposure leads to loss in hepatocyte. Correlation with histopathological results, OP compound-induced cytotoxicity may be modulated through multiple sites including caspase1-3 pathway and also changes in the quantitative criteria of molecular markers of apoptosis in the rat hepatocytes on formation of behavioral skills were characterized by increased in caspase expressions in the hepatocyte.