El-Shafei Reham A, Saleh Rasha M
Department of Pharmacology, Faculty of Veterinary Medicine, Mansoura University, Mansoura, 35516, Egypt.
Department of Animal Physiology, Faculty of Veterinary Medicine, Mansoura University, Mansoura, 35516, Egypt.
Biomed Pharmacother. 2016 Dec;84:314-322. doi: 10.1016/j.biopha.2016.09.005. Epub 2016 Sep 22.
The aim of this study was to evaluate the probable protective effect of vitamin C and vitamin E on diclofenac-induced acute nephrotoxicity using biochemical, molecular and histopathological examination in rats following administration of diclofenac sodium (50mg/kg, I.M).
Ninety male Wister rats were allotted in six equal groups. Rats in the 1st group (control group) were injected with physiological saline, while rats in the 2nd group (C-group) were given vitamin C (100mg/kg orally via stomach tube) for 5 successive days. The 3rd group (E-group) was given vitamin E (250mg/kg orally in diet) for 5 successive days. Rats in the 4th group (D-group) were injected by diclofenac sodium (50mg/kg, I.M) for 5 successive days. The 5th group (DvC-group) was given diclofenac sodium (50mg/kg, I.M) and vitamin C (100mg/kg orally via stomach tube) for 5 successive days. Rats in the 6th group (DvE-group) were given diclofenac sodium (50mg/kg, I.M) and vitamin E (250mg/kg orally in diet) for 5 successive days. Blood samples were collected two days post treatment (1st week of experiment), 2nd and 4th week of the experiment for assessment of urea, creatinine, malondialdehyde, nitric oxide and superoxide dismutase activities. At the end of 4th week, rats were sacrificed and kidneys were excised for biochemical analyses, histopathological evaluation and determination of kidney interleukin-1β, interleukin-18, demsin and nepherin expressions in by reverse transcriptase-polymerase chain reaction (RT-PCR).
The results showed that, diclofenac induced severe kidney damage as indicated by histopathological changes and increased serum oxidative stress parameters. Behavioral changes were monitored; a significant increase in uremia in intoxicated animals was also noted indicating that diclofenac sodium provoked kidney damage in rats. Application of vitamin C (DvC-group) and vitamin E (DvE-group) were found to improve the abovementioned abnormalities.
The present data suggest that, vitamin C and vitamin E might play an important role in reducing oxidative stress and kidney damage induced by diclofenac sodium.
本研究旨在通过生化、分子和组织病理学检查，评估维生素C和维生素E对双氯芬酸诱导的急性肾毒性的可能保护作用，实验中给大鼠腹腔注射双氯芬酸钠（50mg/kg）。
将90只雄性Wister大鼠平均分为6组。第1组（对照组）大鼠注射生理盐水，第2组（C组）大鼠连续5天经胃管口服维生素C（100mg/kg）。第3组（E组）大鼠连续5天经口给予维生素E（250mg/kg）。第4组（D组）大鼠连续5天腹腔注射双氯芬酸钠（50mg/kg）。第5组（DvC组）大鼠连续5天腹腔注射双氯芬酸钠（50mg/kg）并经胃管口服维生素C（100mg/kg）。第6组（DvE组）大鼠连续5天腹腔注射双氯芬酸钠（50mg/kg）并经口给予维生素E（250mg/kg）。在治疗后两天（实验第1周）、实验第2周和第4周采集血样，评估尿素、肌酐、丙二醛、一氧化氮和超氧化物歧化酶活性。在第4周结束时，处死大鼠，取出肾脏进行生化分析、组织病理学评估，并通过逆转录聚合酶链反应（RT-PCR）测定肾脏白细胞介素-1β、白细胞介素-18、demsin和nephrin的表达。
结果表明，双氯芬酸导致严重的肾脏损伤，组织病理学变化和血清氧化应激参数升高表明了这一点。监测了行为变化；还注意到中毒动物的尿毒症显著增加，表明双氯芬酸钠引发了大鼠的肾脏损伤。发现应用维生素C（DvC组）和维生素E（DvE组）可改善上述异常。
目前的数据表明，维生素C和维生素E可能在减轻双氯芬酸钠诱导的氧化应激和肾脏损伤中发挥重要作用。
