Aati Hanan, Aati Sultan Y, Bahr Hebatallah S, Abdel-Sattar Asmaa Ramadan, Embaby Marwa Ahmed, Reda Ahmed M, Abdelmohsen Usama Ramadan, Bringmann Gerhard, Hassan Hossam M, Darwish Mostafa A
Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Dental Health Department, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia.
Front Pharmacol. 2025 Jul 4;16:1584832. doi: 10.3389/fphar.2025.1584832. eCollection 2025.
Cisplatin (CIS) is a productive chemotherapeutic agent that is effective against a variety of cancer types. Its utilization is linked to acute kidney injury and other adverse consequences. Among its toxic effects are oxidative stress, apoptosis as well as inflammation. Saudi Tamarix honey (STH) is a valuable product with plentiful nutritional and health benefits, demonstrating advantageous effects against inflammation and oxidative stress. Therefore, this study examined the potential of STH to prevent oxidative stress, apoptosis, inflammation, and kidney impairment that are induced by CIS in rats, pointing to the entanglement of the Nrf2, the caspase-3, and the IL-6/STAT3/TNF-α signaling pathways.
Histopathological examinations of the kidney were also used to evaluate cisplatin-induced nephrotoxicity. The rats received STH (50, 100 mg/kg) for 10 days and were challenged with a single dose of CIS (7 mg/kg) on day 7.
CIS caused injury to the glomeruli and the tubules, increased lipid peroxidation, TNF-α, IL-6, cleaved caspase-3, and decreased cellular antioxidants in the kidneys of rats. STH effectively prevented tissue injury, and ameliorated oxidative stress, inflammatory markers, in addition to caspase-3 in CIS-administered rats. STH is rich with antioxidants, suppressed STAT3 protein expression, and upregulated Nrf2 in CIS-administered rats. In conclusion, STH mitigated CIS-induced kidney injury by reducing oxidative stress, suppressing STAT3 and caspase-3, inhibiting pro-inflammatory mediators, and enhancing Nrf2 signaling. On the other hand, metabolomic profiling proposed the presence of 15 metabolites belonging to the chemical classes, phenolic acids, flavonoids and sterols, where phenolic acids were the most abundant classes.
顺铂（CIS）是一种有效的化疗药物，对多种癌症类型都有疗效。其使用与急性肾损伤及其他不良后果有关。其毒性作用包括氧化应激、细胞凋亡以及炎症。沙特柽柳蜂蜜（STH）是一种具有丰富营养和健康益处的珍贵产品，对炎症和氧化应激具有有益作用。因此，本研究考察了STH预防CIS诱导的大鼠氧化应激、细胞凋亡、炎症和肾损伤的潜力，指出了Nrf2、半胱天冬酶 - 3和IL - 6/STAT3/TNF - α信号通路之间的关联。
还通过肾脏组织病理学检查来评估顺铂诱导的肾毒性。大鼠连续10天接受STH（50、100毫克/千克），并在第7天接受单次剂量的CIS（7毫克/千克）攻击。
CIS导致大鼠肾脏的肾小球和肾小管损伤，脂质过氧化、TNF - α、IL - 6、裂解的半胱天冬酶 - 3增加，细胞内抗氧化剂减少。STH有效预防了组织损伤，改善了氧化应激、炎症标志物，以及接受CIS处理大鼠的半胱天冬酶 - 3。STH富含抗氧化剂，抑制了接受CIS处理大鼠的STAT3蛋白表达，并上调了Nrf2。总之，STH通过降低氧化应激、抑制STAT3和半胱天冬酶 - 3、抑制促炎介质以及增强Nrf2信号传导减轻了CIS诱导的肾损伤。另一方面，代谢组学分析表明存在15种属于酚酸、黄酮类和甾醇化学类别的代谢物，其中酚酸是最丰富的类别。
