Abd-Elrazek Areeg, Shapana Hadeer, Shukry Wafaa, Galilah Doaa
Department of Physiology, National Organization for Drug Control and Research (NODCAR), 7 Abu Hazem Rd., Al-Haram St.; Madkour Station Pyramids, Giza, Egypt.
Botany Department, Faculty of Science, Mansoura University, Mansoura, Egypt.
Toxicol Res (Camb). 2021 Aug 13;10(4):947-958. doi: 10.1093/toxres/tfab078. eCollection 2021 Aug.
Up-regulation of NF-kB and depletion of glutathione are acceptable mechanisms of Ifosfamide (IFO) renal toxicity. This investigation elucidates the role of free radicals, inflammatory and apoptotic markers in ifosfamide-induced rentoxicity and the protection of species planted in Egypt (, ), and the hybrid between them (). seeds extracts were prepared and phytochemical analyses were assessed. Rats were injected with saline or with IFO alone or in combination with or or orally. Biochemical, gene expression, histological and immune-histological examinations were performed. The results demonstrated that IFO elevated creatinine, sodium, magnesium and urea, along with depleted serum potassium and albumin levels. IFO caused a significant reduction in renal GSH, significant increases in renal MDA, and NOx, and up-regulated iNOS. In addition, IFO treatment showed increase mRNA and protein expression of NF-kB, while down-regulated mRNA and protein expression of Bcl-2, and strong immunohistological expression of caspase-3 as well as BAX in kidney tissues. Different seed extracts significantly enhanced the sharpness of renal injury and improved oxidant responses induced by IFO. extracts down-regulated iNOS, NF-kB expressions, as well as, down-regulated caspase-3 and BAX immunohistological expressions, and up-regulated Bcl-2 expression. . showed a more pronounced protective effect. Histopathological examination was in accordance with biochemical results. Recent results suggest that species ameliorated the renal toxicity of ifosfamide by down-regulation of NOx, iNOS, NF-kB, BAX, caspase-3 and MDA in addition to up-regulation of GSH and Bcl-2.
核因子-κB(NF-κB)的上调和谷胱甘肽的消耗是异环磷酰胺(IFO)肾毒性的可接受机制。本研究阐明了自由基、炎症和凋亡标志物在异环磷酰胺诱导的肾毒性中的作用,以及埃及种植的[物种名称1]、[物种名称2]及其杂交种的保护作用。制备了种子提取物并进行了植物化学分析。大鼠分别注射生理盐水、单独注射IFO或与[提取物名称1]、[提取物名称2]、[提取物名称3]口服联合注射。进行了生化、基因表达、组织学和免疫组织学检查。结果表明,IFO使肌酐、钠、镁和尿素升高,同时血清钾和白蛋白水平降低。IFO导致肾谷胱甘肽显著降低,肾丙二醛(MDA)和氮氧化物(NOx)显著增加,并使诱导型一氧化氮合酶(iNOS)上调。此外,IFO处理显示肾组织中NF-κB的mRNA和蛋白表达增加,而Bcl-2的mRNA和蛋白表达下调,同时半胱天冬酶-3(caspase-3)以及Bax在肾组织中有强烈的免疫组织学表达。不同的种子提取物显著增强了肾损伤的严重程度,并改善了IFO诱导的氧化应激反应。[提取物名称1]提取物下调了iNOS、NF-κB的表达,以及下调了caspase-3和Bax的免疫组织学表达,并上调了Bcl-2的表达。[提取物名称2]显示出更显著的保护作用。组织病理学检查与生化结果一致。最新结果表明,[物种名称]通过下调NOx、iNOS、NF-κB、Bax、caspase-3和MDA,以及上调谷胱甘肽和Bcl-2改善了异环磷酰胺的肾毒性。