心脏毒性是常用抗癌剂环磷酰胺 (Cyclo) 的限制性副作用之一。本研究检查了替米沙坦和纳米螺旋藻 (Sp) 甲醇提取物对环磷酰胺引起的心脏毒性的可能保护作用。大鼠实验组被随机分为九组：对照载体、对照聚合物、替米沙坦（TEL，10 mg/kg）、游离 Sp 提取物（300 mg/kg）、纳米 Sp 提取物（100 mg/kg）、Cyclo（200 mg/kg)、TEL Cyclo、游离 Sp Cyclo 和纳米 Sp Cyclo。联合使用Cyclo的组的治疗方式与未使用Cyclo的相应组相同，在第18天单剂量使用Cyclo。结果表明，Cyclo引起显着的心脏毒性，表现为显着增加155.49%、105.74%与对照组相比，血清谷草酰乙酸转氨酶（SGOT）、乳酸脱氢酶（LDH）、肌酸激酶MB（CK-MB）和心肌肌钙蛋白I（cTnI）酶活性水平分别降低了451.76%和826.07%。控制。此外，心脏谷胱甘肽（GSH）含量和谷胱甘肽过氧化物酶-1（GPX-1）酶活性分别下降65.94%和73.85%。与 TEL 和游离 Sp 相比，纳米 Sp 提取物治疗显示出对改变的生化、组织病理学和免疫组织化学特征的最显着恢复；此外，TEL 和游离 Sp 治疗组的 p-AKT 含量分别降低了 30.64% 和 43.02%，内皮一氧化氮合酶 (eNOS) 免疫反应性分别降低了 60.43% 和 75.30%。有趣的是，nano Sp通过激活beclin-1（36.42％和153.4％）、激活LC3II（69.13％和195％）、下调p62表达（39.68％和62.45％）以及增加基因表达来增强自噬信号。与 TEL 和游离 Sp 治疗组相比，对氧磷酶-1 (PON-1)（分别为 90.3% 和 225.9%）。研究结果表明替米沙坦和纳米 Sp 提取物通过激活抗氧化剂、抗细胞凋亡和自噬信号通路。版权所有 © 2024 Almukainzi、El-Masry、Ibrahim、Saad、El Zahaby、Saleh 和 El-Nagar。

Cardiotoxicity is one of the limiting side effects of the commonly used anticancer agent cyclophosphamide (Cyclo).The possible protective effects of telmisartan and nanoformulated Spirulina platensis (Sp) methanolic extract against Cyclo-induced cardiotoxicity were examined in this study. Experimental groups of rats were randomly divided into nine groups as control vehicle, control polymer, telmisartan (TEL, 10 mg/kg), free Sp extract (300 mg/kg), nano Sp extract (100 mg/kg), Cyclo (200 mg/kg), TEL + Cyclo, free Sp + Cyclo, and nano Sp + Cyclo. The groups with Cyclo combinations were treated in the same manner as their corresponding ones without Cyclo, with a single dose of Cyclo on day 18.The results indicate that Cyclo causes significant cardiotoxicity, manifesting in the form of notable increases of 155.49%, 105.74%, 451.76%, and 826.07% in the serum levels of glutamic oxaloacetic transaminase (SGOT), lactate dehydrogenase (LDH), creatine kinase MB (CK-MB), and cardiac troponin I (cTnI) enzyme activities, respectively, as compared to the control. In addition, the cardiac glutathione (GSH) content and activity of glutathione peroxidase-1 (GPX-1) enzyme decreased by 65.94% and 73.85%, respectively. Treatment with nano Sp extract showed the most prominent restorations of the altered biochemical, histopathological, and immunohistochemical features as compared with those by TEL and free Sp; moreover, reductions of 30.64% and 43.02% in the p-AKT content as well as 60.43% and 75.30% of the endothelial nitric oxide synthase (eNOS) immunoreactivity were detected in the TEL and free Sp treatment groups, respectively. Interestingly, nano Sp boosted the autophagy signal via activation of beclin-1 (36.42% and 153.4%), activation of LC3II (69.13% and 195%), downregulation of p62 expressions (39.68% and 62.45%), and increased gene expressions of paraoxonase-1 (PON-1) (90.3% and 225.9%) compared to the TEL and free Sp treatment groups, respectively.The findings suggest the protective efficiency of telmisartan and nano Sp extract against cardiotoxicity via activations of the antioxidant, antiapoptotic, and autophagy signaling pathways.Copyright © 2024 Almukainzi, El-Masry, Ibrahim, Saad, El Zahaby, Saleh and El-Nagar.