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百里醌治疗对顺铂和柴油机尾气颗粒联合肾毒性和肺毒性的影响。

The effect of thymoquinone treatment on the combined renal and pulmonary toxicity of cisplatin and diesel exhaust particles.

作者信息

Ali Badreldin H, Al Za'abi Mohammed, Shalaby Asem, Manoj Priyadarsini, Waly Mostafa I, Yasin Javed, Fahim Mohamed, Nemmar Abderrahim

机构信息

Departments of Pharmacology and Clinical Pharmacy, College of Medicine and Health Sciences, Sultan Qaboos University, Al Khod 123, Oman.

Departments of Pharmacology and Clinical Pharmacy, College of Medicine and Health Sciences, Sultan Qaboos University, Al Khod 123, Oman

出版信息

Exp Biol Med (Maywood). 2015 Dec;240(12):1698-707. doi: 10.1177/1535370215579013. Epub 2015 Apr 28.

Abstract

Particulate air pollution (PAP) exposure is associated with increased morbidity and mortality, particularly in patients with renal disease. However, there are only a few studies on the interaction between PAP and renal injury, and none on agents that may ameliorate it. We studied the interaction between cisplatin (CP) nephrotoxicity and a single exposure to diesel exhaust particle (DEP) in rats 24 h before sacrifice, and assessed the effect of co-treatment with the active ingredient in Nigella Sativa seed oil, thymoquinone (TQ) thereon. Rats were injected intraperitoneally with CP (6 mg/kg) and four days later, they were exposed intratracheally to DEP (0.5 mg/kg), and were sacrificed 24 h later. Oral TQ (20 mg/kg) was given daily throughout the experimental period. CP alone caused several physiological, biochemical, and histopathological changes that included reduced growth and creatinine clearance, and raised plasma neutrophil gelatinase-associated lipocalin (NGAL), interleukin 6 (IL-6) and C-reactive protein (CRP), creatinine and urea concentrations, and urinary N-acetyl-b-D-glucosaminidase (NAG) activities. It adversely affected several indices of oxidative damage in the kidneys, and induced renal tubular necrosis. Most of these actions were significantly potentiated in rats given both CP and DEP. TQ significantly abrogated many of the effects of CP and DEP, given alone and in combination. These results provide experimental evidence that subjects with renal diseases can be at higher risk from PAP, and that TQ, pending further pharmacological and toxicological studies, can be considered a useful agent in patients with renal diseases and exposed to PAP.

摘要

暴露于颗粒物空气污染(PAP)会增加发病率和死亡率,在肾病患者中尤其如此。然而,关于PAP与肾损伤之间相互作用的研究较少,且尚无关于可改善这种相互作用的药物的研究。我们研究了顺铂(CP)肾毒性与大鼠在处死前24小时单次暴露于柴油废气颗粒(DEP)之间的相互作用,并评估了与黑种草籽油中的活性成分百里醌(TQ)联合治疗对此的影响。大鼠腹腔注射CP(6mg/kg),四天后经气管内暴露于DEP(0.5mg/kg),并在24小时后处死。在整个实验期间每天口服TQ(20mg/kg)。单独使用CP会引起多种生理、生化和组织病理学变化,包括生长和肌酐清除率降低,血浆中性粒细胞明胶酶相关脂质运载蛋白(NGAL)、白细胞介素6(IL-6)和C反应蛋白(CRP)、肌酐和尿素浓度升高,以及尿N-乙酰-β-D-氨基葡萄糖苷酶(NAG)活性增加。它对肾脏的氧化损伤的几个指标产生了不利影响,并导致肾小管坏死。在同时给予CP和DEP的大鼠中,这些作用大多显著增强。单独或联合给予TQ可显著消除CP和DEP的许多作用。这些结果提供了实验证据,表明肾病患者可能因PAP面临更高风险,并且在进一步进行药理和毒理学研究之前,TQ可被视为肾病且暴露于PAP患者的一种有用药物。

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