El Bakary Nermeen M, Abdelhamid Gehan R, Anees Lobna M, Rihan Shaimaa
Radiation Biology Research Department, National Centre for Radiation Research and Technology, Egyptian Atomic Energy Authority, Cairo, Egypt.
Radiation Biology Research Department, National Centre for Radiation Research and Technology, Egyptian Atomic Energy Authority, Cairo, Egypt.
Ecotoxicol Environ Saf. 2025 Sep 1;302:118749. doi: 10.1016/j.ecoenv.2025.118749. Epub 2025 Jul 26.
One of the dangerous consequences of exposure to the heavy metal cadmium (Cd) is cardiotoxicity. The cardiotoxic mechanism of Cd is linked to oxidative damage and inflammation. Trans-resveratrol (RES) had encouraging results in reducing inflammation and oxidative stress. In order to determine how RES and low doses of gamma radiation (LDR) affected cadmium-induced cardiotoxicity in an animal model, this study was designed. It found that RES had a modulatory influence on AMPK-mediated signaling pathways. Five equal groups of forty male albino rats were assigned: control, Cd, Cd+R, Cd+RES, and Cd+RES+R. Rats were given RES (50 mg/kg; for 35 days daily beginning from the second week of cadmium injection, i.p.) and Cd (2 mg/kg i.p.) five days a week for six weeks in a row. After that, they were given LDR (0.75 Gy). Histological and biochemical investigations were performed on the blood and heart samples. Along with a change in lipid profile characteristics, the Cd exposure increased the levels of cardiac damage indicators, creatine kinase-myocardial band (CK-MB), troponin I, and lactate dehydrogenase (LDH). In rat models subjected to Cd, we observed a significant downregulation of key metabolic and antioxidant regulators, including adenosine monophosphate activated protein kinase (AMPK), Sirtuin 1 (SIRT1), Nuclear factor erythroid 2-related factor 2 (NRF2), and Suppressor of cytokine signaling 3 (SOCS3). Conversely, there was a concomitant upregulation of pro-inflammatory and growth-related signaling pathways, as evidenced by increased levels of nuclear factor kappa-light-chain-enhancer of activated B cells NF-κB and mechanistic target of rapamycin (mTOR). However, heart biomarkers (CK-MB, LDH, troponin-1 and lipid profile TG, TC, LDL-C) improved when RES was administered either by itself or in conjunction with LDR. Additionally, the results of the biochemical studies were corroborated by the histological evaluations of cardiac tissues. According to our results, it can be concluded that Cd exposure causes significant cardiotoxicity by promoting oxidative damage and inflammation, disrupting key metabolic and antioxidant pathways. Resveratrol, either alone or combined with low-dose gamma radiation, effectively attenuates these adverse effects, improving cardiac function and tissue integrity. According to this study, a novel therapeutic possibility for the treatment of cardiotoxicity may be a combination of LDR and RES.
接触重金属镉（Cd）的危险后果之一是心脏毒性。Cd的心脏毒性机制与氧化损伤和炎症有关。反式白藜芦醇（RES）在减轻炎症和氧化应激方面取得了令人鼓舞的成果。为了确定RES和低剂量γ辐射（LDR）如何影响动物模型中镉诱导的心脏毒性，设计了本研究。研究发现RES对AMPK介导的信号通路具有调节作用。将40只雄性白化大鼠平均分为五组：对照组、Cd组、Cd+R组、Cd+RES组和Cd+RES+R组。大鼠连续六周每周五天腹腔注射Cd（2mg/kg），从注射镉的第二周开始每天腹腔注射RES（50mg/kg，持续35天）。之后，给予它们LDR（0.75Gy）。对血液和心脏样本进行了组织学和生化研究。随着脂质谱特征的变化，Cd暴露增加了心脏损伤指标肌酸激酶同工酶（CK-MB）、肌钙蛋白I和乳酸脱氢酶（LDH）的水平。在Cd处理的大鼠模型中，我们观察到关键代谢和抗氧化调节因子的显著下调，包括腺苷单磷酸活化蛋白激酶（AMPK）、沉默调节蛋白1（SIRT1）、核因子E2相关因子2（NRF2）和细胞因子信号转导抑制因子3（SOCS3）。相反，促炎和生长相关信号通路伴随上调，活化B细胞核因子κB轻链增强子（NF-κB）和雷帕霉素靶蛋白（mTOR）水平升高证明了这一点。然而，单独给予RES或与LDR联合使用时，心脏生物标志物（CK-MB、LDH、肌钙蛋白-1和脂质谱甘油三酯、总胆固醇[TC]、低密度脂蛋白胆固醇[LDL-C]）有所改善。此外，心脏组织的组织学评估证实了生化研究的结果。根据我们的结果，可以得出结论，Cd暴露通过促进氧化损伤和炎症、破坏关键代谢和抗氧化途径而导致显著的心脏毒性。白藜芦醇单独或与低剂量γ辐射联合使用可有效减轻这些不良反应，改善心脏功能和组织完整性。根据本研究，LDR和RES联合使用可能是治疗心脏毒性的一种新的治疗可能性。
