1 Department of Physiology, Faculty of Medicine, Beni-Suef University, Beni Suef, Egypt.
2 Department of Anatomy, Faculty of Medicine, Cairo University, Giza, Egypt.
Hum Exp Toxicol. 2019 Mar;38(3):321-335. doi: 10.1177/0960327118812166. Epub 2018 Nov 20.
Despite being one of the most nephrotoxic drugs, gentamicin (GM) remains a mainstay as a first-choice agent in a vast variety of clinical situations owing to its superlative efficiency as a broad-spectrum antibiotic in treating several life-threatening bacterial infections. This urgently calls for the need for in-depth analysis of the mechanisms governing GM-induced nephrotoxicity and entails the necessity of presenting novel protective agents capable of ameliorating those renal deleterious effects. The reactive oxygen species and redox-sensitive transcription factors in GM-induced nephrotoxicity have recently called attention.
This study has been designed to shed light on the possible mechanisms of GM-induced nephrotoxicity and to provide a consensus set of histopathological, immunohistochemical, genetic and biochemical parameters elucidating the protective role of vitamin D against this nephrotoxicity.
Twenty-four adult male albino rats were equally divided into four groups: group I (control group), group II (GM), group III (GM + vitamin D) and group IV (vitamin D only). Kidney function tests, histopathological examination, gene expression of nuclear factor 2, nuclear factor kappa beta (NF-κB) and western blot of NF-κB p65, assessment of glutathione peroxidase and nicotinamide adenine dinucleotide phosphate oxidase (NADPH) oxidase by ELISA, as well as immunohistochemical evaluation of inducible nitric oxide, malondialdehyde, 8-hydroxy 2 deoxyguanine and vitamin D receptor, have been carried out.
The kidney function deterioration, tissue oxidative stress development and the histopathological changes induced by GM were significantly attenuated by vitamin D administration.
Vitamin D attenuates GM nephrotoxicity through its antioxidant properties and prevention of DNA damage.
尽管庆大霉素（GM）是最具肾毒性的药物之一，但由于其作为广谱抗生素在治疗多种危及生命的细菌感染方面的卓越功效，它仍然是各种临床情况下的首选药物。这就迫切需要深入分析导致 GM 肾毒性的机制，并需要提出能够改善这些肾脏有害作用的新型保护剂。GM 诱导的肾毒性中的活性氧和氧化还原敏感转录因子最近引起了关注。
本研究旨在阐明 GM 诱导的肾毒性的可能机制，并提供一组共识的组织病理学、免疫组织化学、遗传和生化参数，阐明维生素 D 对这种肾毒性的保护作用。
将 24 只成年雄性白化大鼠平均分为四组：第 I 组（对照组）、第 II 组（GM）、第 III 组（GM + 维生素 D）和第 IV 组（仅维生素 D）。进行肾功能试验、组织病理学检查、核因子 2、核因子 kappa beta（NF-κB）的基因表达和 NF-κB p65 的 Western blot、通过 ELISA 评估谷胱甘肽过氧化物酶和烟酰胺腺嘌呤二核苷酸磷酸氧化酶（NADPH）氧化酶，以及诱导型一氧化氮、丙二醛、8-羟基 2-脱氧鸟苷和维生素 D 受体的免疫组织化学评估。
维生素 D 的给药显著减轻了 GM 引起的肾功能恶化、组织氧化应激发展和组织病理学变化。
维生素 D 通过其抗氧化特性和防止 DNA 损伤来减轻 GM 肾毒性。
