Diazinon (DZN) is one of the most widely used insecticides in agricultural pest control. Previous studies have shown that DZN may induce hepatotoxicity. Reactive oxygen species and apoptosis pathways are involved in the toxicity of DZN. Crocin, a constituent of saffron, has hepatoprotective effects due to its antioxidant activity. In this study, we examined the effects of subacute DZN exposure and ameliorating effect of crocin on lipid peroxidation and pathological changes in rat liver. Moreover, protein levels of activated and total caspases-3 and -9 and Bax/Bcl-2 ratio were measured. Five groups of rats were used in the experiment. Corn oil (control), DZN (15 mg/kg per day, orally) and crocin (12.5, 25 and 50 mg/kg per day, intraperitoneally in combination with DZN) were given to male Wistar rats (n = 6) for 4 weeks. The level of malondialdehyde (MDA) increased significantly in DZN group compared with the control group (p < 0.05). MDA level decreased significantly in the group that received DZN plus 25 mg crocin (p < 0.001). No gross or histological evidence of treatment-related damage to the liver after oral exposure to DZN was observed. DZN also induced apoptosis through activation of caspases-9 and -3 and increasing Bax/Bcl-2 ratio. Crocin attenuated the activation of caspases and reduced the Bax/Bcl-2 ratio. It is concluded that subacute exposure to DZN induces oxidative stress-mediated apoptosis and crocin may reduce DZN-induced hepatotoxicity.

Polyethylenimine (PEI) is a polycation widely used for successful gene delivery both in vitro and in vivo experiments. However, different studies showed that PEI could be cytotoxic to transfected cells, and the mechanism of toxicity is poorly understood. Identification of PEI-interacting proteins may help in understanding the toxicity pathways. In this study, we investigated proteins that could interact with PEI in human colorectal adenocarcinoma cells (HT29). In order to identify the proteins interacting with PEI, PEI was immobilized to sepharose beads as solid matrix. The HT29 cell lysate were passed through the matrix. PEI-bound proteins were isolated, and further separation was performed by two-dimensional gel electrophoresis. After gel digestion, proteins were identified by matrix-assisted laser desorption/ionization–time-of-flight (TOF)/TOF mass spectrometry. Our data indicated that most of the identified PEI-interacting proteins such as shock proteins, glutathione- S-transferases, and protein disulfide isomerase are involved in apoptosis process in cells. Thus, although this is a preliminary experiment implicating the involvement of some proteins in PEI cytotoxicity, it could partly explain the mechanism of PEI cytotoxicity in cells.

Diazinon, an organophosphorus insecticide, is employed to control pests in agriculture. Diazinon may contaminate the environment during the manufacturing process or agricultural application. Previous studies have revealed that diazinon may induce alteration in the protein profile of the liver. Here, a proteomics approach was used to investigate the effects on the protein profile in the liver of rats of subacute oral exposures at 15 mg/kg of diazinon. Liver proteins were separated using 2D-PAGE, and stained by MS-compatible silver staining and/or the fluorescent SYPRO® Ruby protein gel stain. Gels were scanned and analyzed using the Image Master software. Differentially displayed protein species were identified using MALDI-TOF/TOF and MASCOT software. Significantly altered protein species were identified to be involved in apoptosis, cell metabolism, transport, and antioxidant systems. Exposure to diazinon decreased levels of some species of catalase, peroxiredoxin-6, 3-ketoacyl-CoA thiolase, and glucose regulated protein78, whereas the level of protein disulfide-isomerase A3 increased. Our results suggested that diazinon may induce hepatotoxicity through oxidative stress, apoptosis, and metabolic disorders in rat liver.

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