تالیدوماید آسیب حاد کلیوی ناشی از گلیسرول را بوسیله مهار NF-κB، NLRP3 inflammasome، COX-2 و سایتوکاین های التهابی، کاهش می دهد

امیرشاهرخی, کیوان (1400) تالیدوماید آسیب حاد کلیوی ناشی از گلیسرول را بوسیله مهار NF-κB، NLRP3 inflammasome، COX-2 و سایتوکاین های التهابی، کاهش می دهد. Cytokine ــ 144 (155574). pp. 1-5. شاپا 1043-4666

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Thalidomide reduces glycerol-induced acute kidney injury by inhibition of NF-κB, NLRP3 inflammasome, COX-2 and inflammatory cytokines

English Abstract

Acute kidney injury (AKI) is an important clinical complication of rhabdomyolysis. The inflammatory processes are involved in the pathogenesis of AKI induced by rhabdomyolysis. Thalidomide is an anti-inflammatory agent that has been used in the treatment of inflammatory disorders. The aim of this study was to investigate the therapeutic effect of thalidomide and its underlying mechanisms on a mouse model of rhabdomyolysis-induced AKI. Mice were injected with a single dose of glycerol (50%, 10 ml/kg, im) to induce AKI, and treated with thalidomide (40 and 80 mg/kg/day, orally) for 2 days. Renal tissue and blood samples were collected for histological and biochemical analysis. In thalidomide treated mice, blood urea nitrogen (BUN) (59.3 ± 19.6 vs. 223 ± 33 mg/dl), plasma creatinine (0.58 ± 0.3 vs. 1.28 ± 0.3 mg/dl), relative kidney weight (0.93 ± 0.13% vs. 1.22 ± 0.1%) and histopathological damage (1.5 ± 0.8 vs. 3.3 ± 1.1 score) were significantly lower as compared to the glycerol group. The results also showed that the levels of malondialdehyde (MDA) (0.13 ± 0.02 vs. 0.2 ± 0.01 µM/mg), myeloperoxidase (MPO) (0.1 ± 0.05 vs. 0.25 ± 0.02 U/mg) and the expression of nuclear factor kappa B (NF-κB) (1.7-fold), NLRP3 inflammasome (1.4-fold) and cyclooxygenase (COX)-2 (3-fold) in renal tissue were significantly lower in thalidomide treated group than those in the glycerol group. Thalidomide treatment resulted in lower renal pro-inflammatory cytokines tumor necrosis factor (TNF)-α (6.7 ± 0.8 vs. 12.3 ± 1.2 ng/ml), interleukin (IL)-1β (3.2 ± 0.5 vs. 5.1 ± 0.3 pg/mg), IL-6 (24.7 ± 2.4 vs. 33 ± 3 pg/mg) and transforming growth factor (TGF)-β1 (0.6 ± 0.17 vs. 1.56 ± 0.24 ng/ml) than those in the glycerol treated mice. In addition the levels of monocyte chemoattractant protein (MCP)-1 (9.5 ± 1 vs. 12.8 ± 1.1 pg/mg) and intercellular adhesion molecule (ICAM)-1 (22.8 ± 7.8 vs. 53.3 ± 5.5 pg/mg) were significantly lower in renal tissue of mice treated with thalidomide as compared to the glycerol treated mice. In conclusion these data revealed that thalidomide may be a potential therapeutic approach against rhabdomyolysis-induced AKI through inhibition of inflammatory responses.

Item Type:Article
زبان سند : انگلیسی
نویسنده مسئول :کیوان امیرشاهرخی
Additional Information:IF: 3.861 Indexed in: ISI, PubMed/Medline, Scopus, Embase
کلیدواژه ها (انگلیسی):Thalidomide; acute kidney injury; rhabdomyolysis; NF-κB; NLRP3; cytokines; inflammation
Subjects:QV pharmacology
Divisions:School of Pharmacy > Department of Pharmacology
ID Code:14292
Deposited By: Dr Kivan Amir Shahrikhi
Deposited On:13 May 1400 07:17
Last Modified:13 May 1400 07:17

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