Department of Medical Physiology, Faculty of Medicine, Assiut University, Assiut, Egypt.
J Physiol Biochem. 2013 Mar;69(1):1-13. doi: 10.1007/s13105-012-0182-y. Epub 2012 Jun 23.
Hepatic injury by acetaminophen (APAP) has been extensively studied, although the alterations of renal functions and arterial blood pressure (ABP) after APAP exposure are still uncertain, and the impact of Nigella sativa oil (NSO) in this case is poorly defined. Sixty adult male albino rats were involved in two sets of experiments. The first was exposed to a single high dose of APAP (2.5 g/kg) orally preceded by 4 ml NSO/kg orally, while the second received 750 mg APAP/kg/day orally for seven consecutive days and was pretreated with 2 ml NSO/kg/day. Proximal tubular injury was assessed by laboratory and histological studies, and arterial blood pressure was recorded in all animals. In both experiments, urinary α-glutathione S-transferase and neutral endopeptidase, and microproteinuria were dramatically increased early indicating glomerulus and proximal tubule dysfunction that was mediated by raising 8-isoprostanes. Concomitantly, urinary albumin, total protein, creatinine, urea, glomerular filtration rate, Na and K levels, plasma creatinine, and urea were all changed significantly after APAP administration. Currently, ABP increased significantly after APAP which was mostly mediated by renal impairment and increased both renin activity and aldosterone secretion. Pretreatment with NSO produced significant normalization of physiological parameters as well as suppression of structural changes. In conclusion, measurement of urinary biomarkers can be considered a powerful tool for early screening of renal injury and alteration of ABP after APAP treatment. Concomitant administration of NSO can counterbalance these detrimental effects.
对乙酰氨基酚(APAP)引起的肝损伤已有广泛研究,尽管 APAP 暴露后肾功能和动脉血压(ABP)的变化仍不确定,而且黑种草籽油(NSO)在这种情况下的影响也尚未明确。本研究涉及 60 只成年雄性白化大鼠,分两组实验。第一组大鼠先口服给予 2.5g/kg 的 APAP,同时口服给予 4ml/kg 的 NSO,第二组大鼠则连续 7 天口服给予 750mg/kg 的 APAP,并同时每日给予 2ml/kg 的 NSO。通过实验室和组织学研究评估近端肾小管损伤,记录所有动物的动脉血压。在这两个实验中,尿液α-谷胱甘肽 S-转移酶和中性内肽酶以及微蛋白尿都显著增加,这表明肾小球和近端肾小管功能障碍,这是由 8-异前列腺素升高介导的。同时,APAP 给药后,尿白蛋白、总蛋白、肌酐、尿素、肾小球滤过率、Na 和 K 水平、血浆肌酐和尿素均发生显著变化。目前,APAP 后 ABP 显著升高,这主要是由肾功能损害引起的,同时还增加了肾素活性和醛固酮分泌。NSO 的预处理可显著使生理参数正常化,并抑制结构变化。总之,尿液生物标志物的测量可被认为是早期筛查 APAP 治疗后肾损伤和 ABP 改变的有力工具。同时给予 NSO 可以抵消这些有害影响。