Hamza Ali, Zadi Sayda Snober Fatima, Salar Muhammad Zaid, Ijaz Muhammad Umar, Al-Ghanim Khalid A, Ishtiaq Ayesha
Department of Zoology, Wildlife and Fisheries, University of Agriculture, Faisalabad, Pakistan.
Department of Zoology, Wildlife and Fisheries, University of Agriculture, Faisalabad, Pakistan.
J Trace Elem Med Biol. 2025 Apr;88:127597. doi: 10.1016/j.jtemb.2025.127597. Epub 2025 Jan 14.
Cadmium (Cd) is a toxic heavy metal present in environment that has potential to instigate renal toxicity. Didymin (DDM) is a natural flavone, which shows anti-oxidant, anti-inflammatory and antiapoptotic nature. Therefore, the current study was formulated to appraise attenuative potential of DDM against Cd instigated nephrotoxicity.
Forty-eight albino rats were divided into four equal groups, including control, Cd (5 mg/kg) inebriated group, Cd + DDM (5 mg/kg + 1 mg/kg) concurrent-treated group, as well as DDM (1 mg/kg) alone treated group. The trial was conducted for 30 days and then the rats were anesthetized, decapitated and further analyses were performed.
The results demonstrated that Cd treatment lowered the expressions of Nrf-2 and its anti-oxidant genes while escalating Keap-1 expression. Cd exposure downregulated the activities of antioxidant enzymes, SOD, GSR, CAT, HO-1, GPx, GST & GSH contents, while the levels of MDA and ROS were escalated. Furthermore, Cd exposure lowered the levels of creatinine clearance and albumin, while increasing the levels of urobilinogen, urinary proteins, urea, creatinine, NGAL and KIM-1. Moreover, Cd intoxication also augmented the levels of inflammatory indices including, IL-1β, NF-κB, TNF-α, IL-6 and COX-2. Additionally, Cd exposure reduced the expressions of Bcl-2, while increasing Bax and caspase-3 expressions. In addition to this, Cd also provoked multiple histological injuries in the renal tissues of the rats. However, DDM supplementation markedly recovered the renal tissues from the Cd induced damages.
In conclusion, DDM protected the renal tissues from Cd-provoked damages due to its antiapoptotic, anti-oxidant and anti-inflammatory efficacy.
镉（Cd）是环境中存在的一种有毒重金属，具有引发肾毒性的潜力。二氢杨梅素（DDM）是一种天然黄酮，具有抗氧化、抗炎和抗凋亡特性。因此，本研究旨在评估DDM对镉引发的肾毒性的减轻作用。
48只白化大鼠被分为四组，每组数量相等，包括对照组、镉（5mg/kg）中毒组、镉+DDM（5mg/kg + 1mg/kg）联合治疗组以及单独使用DDM（1mg/kg）治疗组。试验持续30天，然后将大鼠麻醉、断头并进行进一步分析。
结果表明，镉处理降低了Nrf-2及其抗氧化基因的表达，同时提高了Keap-1的表达。镉暴露下调了抗氧化酶SOD、GSR、CAT、HO-1 GPx、GST的活性以及GSH含量，而MDA和ROS水平升高。此外，镉暴露降低了肌酐清除率和白蛋白水平，同时增加了尿胆原、尿蛋白、尿素、肌酐、中性粒细胞明胶酶相关脂质运载蛋白（NGAL）和肾损伤分子-1（KIM-1）的水平。此外，镉中毒还增加了包括IL-1β、NF-κB、TNF-α、IL-6和COX-2在内的炎症指标水平。另外，镉暴露降低了Bcl-2的表达，同时增加了Bax和caspase-3的表达。除此之外，镉还在大鼠肾组织中引发了多种组织学损伤。然而，补充DDM显著使肾组织从镉诱导的损伤中恢复。
总之，由于其抗凋亡、抗氧化和抗炎功效，DDM保护了肾组织免受镉引发的损伤。
