PDTC Attenuates Radiation Induced Heart Damage Through Inhibition of Activation of NF-κB and Its Downstream Pathway in Rats

Abstract

To documented whether pyrrolidine dithiocarbamate (PDTC) can attenuate damage by inhibition of excessive activation of NF-κB and hypoxia-inducible factor 1α(HIF-1α), as its downstream pathway in rat model of acute radiation induced heart damage (RIHD). Twenty one male adult Sprague-Dawley (SD) rats were randomly divided into 3 groups: control, irradiation and PDTC plusirradiation. Rats in irradiation group and PDTC+ irradiation group were underwent heart irradiation with a single fraction of 20.0 Gy. The dose of PDTC was calculatedon the rat’s body weight (120mg/kg), and then was administrated intraperitonally 30 minutes prior to radiation regularly once a day until the 14th day. On the 14th day，morphological structure of myocardial tissue was observed. Total collagen was determined by preparing tissue sections with Masson’s trichrome stain, and collagen volume fraction (CVF) was applied for semi-quantitative analysisof myocardial collagen. The protein expression levels of NF-κB members like P50 and P65, HIF-1α, connective tissue growth factor (CTGF), as well as collagen type I (COL-1) were quantitatively analyzed by Western blot. The mRNA expression of them were determined by Quantitative Real-time PCR (qPCR). Compared with irradiation group, myocardial edema was alleviated in PDTC + irradiation group significantly, accompanied by myocardial interstitial inflammatory cell infiltration and fibroblast mitigated. The result of Masson’s trichrome staining showed that the deposition of collagen fiber in the interstitial tissue was declined.The values of CVF were 9.99 ± 0.32% and 22.05 ± 0.21% in PDTC + irradiation group andin irradiation group, respectively (P＜0.05).The protein and mRNA expression of P50, P65, and HIF-1αshoweddown-regulated levels after treatment with PDTC, but there was only a declining tendency of the protein and mRNA expression level of CTGF.The expression of COL-1 protein in the PDTC + irradiation group was lower than that in the irradiation group (P＜0.05), andCOL-1mRNA had a down-regulated tendency expression as well. PDTC could alleviate the development ofmyocardial inflammation and fibrosis in early stagein rat RIHD model.It may inhibit the activation of NF-κB and HIF-1α transcription.