RESUMO
Objective: Radiation-induced heart damage (RIHD) is becoming an increasing concern due to offsetting clinical benefits of radiotherapy to a certain extent. Pyrrolidine dithiocarbamate (PDTC) as an antioxidant has been implicated in cardioprotective effects. We aimed to investigate whether pyrrolidine dithiocarbamate could attenuate heart damage at an early stage post-irradiation and unveil the potential mechanisms. Methods: A total of 15 adult male Sprague-Dawley rats were randomized into the control, irradiation (IR), and PDTC plus irradiation (PDTC + IR) groups. Hearts were irradiated with a single fraction of 20.0 Gy. Rats received daily intraperitoneal injection of PDTC for 14 days. At the 14th day post-irradiation, echocardiography was performed, and rats were killed. Morphological damage was examined by hematoxylin-eosin (HE) stain and Masson's trichrome stain. The collagen volume fraction (CVF) was applied for semi-quantitative analysis. The protein levels were analyzed by Western blot and mRNA levels by quantitative real-time PCR. Results: No significant damage to systolic function of left ventricular was induced at an early stage post-irradiation. HE staining of cardiac tissue showed that the disordered arrangement of myocardial cells and abnormal cell infiltration were alleviated in the PDTC + IR group. The increased CVF in the irradiation group was inhibited in the PDTC + IR group (22.05 ± 2.64% vs. 9.99 ± 1.65%, p < 0.05). The protein levels of nuclear factor-kappa B (NF-κB), hypoxia-inducible factor-1α (HIF-1α), and COL-1 were downregulated after treatment with PDTC (p < 0.05), and there was a declining trend in the protein of the connective tissue growth factor (CTGF). The mRNA expression of NF-κB and HIF-1α in the PDTC plus irradiation group was lower than that in the irradiation group (p < 0.05), and there was a declining trend in the mRNA expression of the connective tissue growth factor and COL-1. Conclusion: PDTC alleviates myocardial cell disordered arrangement, abnormal cell infiltration, and pro-fibrotic change at an early stage in rats with radiation-induced heart damage. Such a protective effect is closely associated with the downregulation of NF-κB.
RESUMO
The second excited (1)Sigma(g)(+) state of the hydrogen molecule, the so-called GK state, has a potential energy curve with double minima. At the united atom limit it converges to the 1s3d configuration of He. At large internuclear distances R, it dissociates to two separated atoms, one in the ground state and another in the 2p excited state. Radial pair density calculations and natural orbital analyses reveal unusual effect of electron correlation around the K minimum of the potential energy curve. As R>2.0 a.u., a natural orbital of sigma(u) symmetry joins the two natural orbitals of sigma(g) symmetry at smaller R. The average interelectronic distance decreases as the internuclear distance increases from R=2.0 to 3.0 a.u. Around R=3.0 a.u. the singly peaked pair density curve splits into two peaks. The inner peak can be attributed to the formation of the ionic electron configuration (1s)(2), where both 1s electrons are on the same nucleus. As the two 1s electrons run into different nuclei, one of the two 1s electrons is promoted to the 2p state, which results in the outer peak in the pair density curve. The Rydberg 1s2p configuration persists as the nuclei stretch, and becomes dominant at large R where four natural orbitals, two of sigma(g) and two of sigma(u) symmetry, become responsible.