PDTC attenuates radiation-induced heart damage by inhibiting the activation of NF-κB and its downstream signaling pathways in rats

Abstract

Objective To investigate whether pyrrolidine dithiocarbamate (PDTC) can attenuate the acute radiation-induced heart damage (RIHD) by inhibiting the activation of NF-κB and its downstream signaling pathways in rat models. Methods Twenty-one male adult Sprague-Dawley (SD) rats were randomly divided into the blank control, irradiation and PDTC plus irradiation groups (n=7 for each group). In the irradiation and PDTC+ irradiation groups, the rats received 6 MV X-ray at a single fraction of 20.0 Gy. In the PDTC+ irradiation group, intraperitonal injection of PDTC was administered at a dose of 120 mg/kg body weight, 30 minutes prior to radiation, once daily for 1-14 days. On the 14th day, pathological changes of myocardial tissue were observed. Masson’s trichrome staining was performed to calculate the collagen volume fraction (CVF) of myocardial cells. The expression levels of NF-κB family members including p50, p65, HIF-1α, connective tissue growth factor (CTGF) and collagen type 1(COL-1) proteins and mRNA were quantitatively measured by Western blot and quantitative real-time PCR (qPCR). Statistical analysis was conducted by using t-test. Results HE staining demonstrated that compared with the irradiation group, the severity of myocardial edema was alleviated, the infiltration of inflammatory cells was mitigated and the quantity of fibroblasts was reduced in the PDTC+ irradiation group. Masson’s trichrome staining revealed that PDCT intervention could decrease the deposition of collagen fiber in the interstitial tissues. Semi-quantitative analysis demonstrated that the CVF value in the PDTC+ irradiation group was (9.99±0.32)%, significantly lower compared with (22.05±0.21)% in the irradiation group (P 0.05), and the expression levels of COL-1 protein and mRNA were equally inclined to decrease (P 0.05). Conclusion PDTC can alleviate the acute RIHD by suppressing the activation of NF-κB and its downstream HIF-1α transcription. Key words: Acute radiation-induced heart damage; Nuclear factor-κB; Pyrrolidine dithiocarbamate; Hypoxia-inducible factor-1α; Connective tissue growth factor