title: The effects of rotenone-induced toxicity via the NF-κB-iNOS pathway in rat liver.
abstract: Rotenone has been used as a pesticide for many years, it is an environmental poison reported to cause neurological diseases. However, the effects of rotenone on the rat liver are unclear, as are the mechanisms of toxicity. In the present study, Sprague-Dawley (SD) rats were divided into five groups: control, dimethyl sulfoxide (DMSO), rotenone low-dose (1 mg/kg), rotenone mid-dose (2 mg/kg) and rotenone high-dose (4 mg/kg). The treatments were orally administered daily for 28 days, we assessed health status, mRNA expression levels of inflammatory factors, protein levels, nitric oxide (NO) content and histological changes. The results showed that body weight was significantly decreased in each rotenone group in a dose-dependent manner, compared with the control group. Rotenone significantly increased the mRNA levels of cyclooxygenase-2 (COX-2), nuclear factor kappaB (NF-κB), prostaglandin E2(PGE2), inducible nitric oxide synthase (iNOS) and tumor necrosis factor (TNF-α) in each rotenone group compared with the control group, except iNOS and TNF-α mRNA expression in the low-dose group. The protein levels of COX-2 were significantly higher in each rotenone group compared with the control group, NF-κB protein expression were significantly higher in the rotenone mid and high-dose groups, but not in the low-dose group, compared with the control group, similar changes were observed in NO content. Additionally, histological analysis revealed that the most severe tissue damage occurred in the high-dose group. These results indicated that rotenone has toxic effect in rat liver relating to inflammatory factors. Our findings provide insight into the mechanisms of rotenone hepatotoxicity.
authors.affiliation: a Department of Veterinary Medicine , Northeast Agricultural University , Harbin , China.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Jiang
authors.affiliation: a Department of Veterinary Medicine , Northeast Agricultural University , Harbin , China.
authors.forename: Xinxin
authors.initials: X
authors.lastname: Feng
authors.affiliation: a Department of Veterinary Medicine , Northeast Agricultural University , Harbin , China.
authors.forename: Hui
authors.initials: H
authors.lastname: Huang
authors.affiliation: a Department of Veterinary Medicine , Northeast Agricultural University , Harbin , China.
authors.forename: Lin
authors.initials: L
authors.lastname: Liu
authors.affiliation: a Department of Veterinary Medicine , Northeast Agricultural University , Harbin , China.
authors.forename: Lu
authors.initials: L
authors.lastname: Qiao
authors.affiliation: a Department of Veterinary Medicine , Northeast Agricultural University , Harbin , China.
authors.forename: Binqing
authors.initials: B
authors.lastname: Zhang
authors.affiliation: a Department of Veterinary Medicine , Northeast Agricultural University , Harbin , China.
authors.forename: Wenhui
authors.initials: W
authors.lastname: Yu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D007306:Insecticides / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012402:Rotenone / Q000633:toxicity*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D007306:Insecticides; D016328:NF-kappa B; D012402:Rotenone; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat
keywords: Rotenone; Sprague–Dawley rat; histological evaluation; inflammatory factor; liver