1 Department of Pharmacology, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Kingdom of Saudi Arabia.
2 Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia.
Hum Exp Toxicol. 2019 May;38(5):588-597. doi: 10.1177/0960327119829521. Epub 2019 Feb 11.
In the present study, the protective effect of Roflumilast (ROF, a selective phosphodiesterase (PDE-4) inhibitor) was investigated against cadmium (Cd)-induced nephrotoxicity in rats.
A total of 24 rats were selected and randomly divided into four groups ( n = 6). Group 1 served as the control; groups 2-4 administered with CdCl (3 mg/kg, i.p.) for 7 days; groups 3 and 4 were co-administered with ROF in doses of 0.5 and 1.5 mg/kg, orally for 7 consecutive days. Nephrotoxicity was evaluated by measuring urine volume, urea and creatinine levels in urine and serum. Oxidative stress was confirmed by measuring malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) levels in kidney tissue followed by histopathological studies.
CdCl administration results in a significant ( p < 0.01) decrease in urine volume, urea, and creatinine levels in urine, as well as GSH, SOD, and CAT levels in renal tissue. In addition, Cd also produced significantly increased ( p < 0.01) urea and creatinine levels in serum and TBARS levels in renal tissues. Rats treated with ROF significantly ( p < 0.01) restore the altered levels of kidney injury markers, nonenzymatic antioxidant, as well as depleted enzymes in dose-dependent manner. An increased expression of NF-κB p65 and decreased expression of GST and NQO1 in the Cd only treated group were significantly reversed by high dose of ROF (1.5 mg/kg). Histopathological changes were also ameliorated by ROF administration in Cd-treated groups.
In conclusion, ROF treatment showed protective effect against renal damage and increased oxidative stress induced by Cd administration.
在本研究中，研究了罗氟司特（ROF，一种选择性磷酸二酯酶（PDE-4）抑制剂）对大鼠镉（Cd）诱导的肾毒性的保护作用。
选择 24 只大鼠并随机分为四组（n=6）。第 1 组为对照组；第 2-4 组腹腔注射 CdCl2（3mg/kg），连续 7 天；第 3 和第 4 组分别给予 0.5 和 1.5mg/kg 的 ROF，连续 7 天。通过测量尿液量、尿液和血清中尿素和肌酐水平来评估肾毒性。通过测量肾组织中丙二醛（MDA）、谷胱甘肽（GSH）、超氧化物歧化酶（SOD）和过氧化氢酶（CAT）水平来证实氧化应激，然后进行组织病理学研究。
CdCl2 给药导致尿液量、尿素和肌酐水平以及肾组织中 GSH、SOD 和 CAT 水平显著降低（p<0.01）。此外，Cd 还导致血清中尿素和肌酐水平以及肾组织中 TBARS 水平显著升高（p<0.01）。ROF 治疗可显著（p<0.01）以剂量依赖的方式恢复肾损伤标志物、非酶抗氧化剂和耗竭酶的改变水平。仅用 Cd 处理的组中 NF-κB p65 的表达增加和 GST 和 NQO1 的表达减少被高剂量的 ROF（1.5mg/kg）显著逆转。在 Cd 处理组中，ROF 给药还改善了组织病理学变化。
总之，ROF 治疗对 Cd 给药引起的肾损伤和氧化应激增加具有保护作用。
