Low-dose angiotensin AT1 receptor β-arrestin-biased ligand, TRV027, protects against cisplatin-induced nephrotoxicity

Esmaeeli, A and Ebrahimi, F and Tanha, K and Assadi, M and Seyedabadi, M (2020) Low-dose angiotensin AT1 receptor β-arrestin-biased ligand, TRV027, protects against cisplatin-induced nephrotoxicity. Pharmacological Reports, 72 (6). pp. 1676-1684. ISSN 17341140

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Official URL: https://link.springer.com/article/10.1007/s43440-0...


Recruitment of β-arrestin to G protein-coupled receptors (GPCRs), initially described to cause receptor desensitization, has recently been shown to take active roles in cell signaling. We investigated the effects of TRV027, an angiotensin AT1 receptor β-arrestin-biased ligand, as well as losartan and valsartan on cisplatin-induced kidney injury. Method: Male Sprague–Dawley rats were treated with angiotensin receptor ligands (1 or 10 mg/kg/day) with or without cisplatin, and kidney variables were monitored using animal SPECT, histopathology, and serum parameters. Results: TRV027, losartan, and valsartan did not alter renal dimercaptosuccinic acid (DMSA) uptake, histopathological manifestations of kidney injury, blood urea nitrogen (BUN), and creatinine or Na+ and K+ levels, per se. However, when rats co-treated with cisplatin and either of the AT1 receptor blockers at higher doses, we observed aggravation of cisplatin-induced reduction of radiotracer uptake but improvement of cisplatin-induced hypokalemia, and insignificant effect on histological findings. Furthermore, we noted an additional increase in cisplatin-induced augmentation of BUN and creatinine levels in cisplatin plus valsartan group. TRV027 (1 mg/kg/day) inhibited cisplatin adverse effects on radiotracer uptake, kidney histology, BUN, and creatinine as well as electrolyte levels, but it failed to produce protective effects at higher dose (10 mg/kg/day). Conclusion: Low-dose TRV027 may offer potential benefits in kidney injury due to cisplatin.

Item Type: Article
Uncontrolled Keywords: Angiotensin receptor Biased ligand Cisplatin Losartan Nephrotoxicity TRV027 Valsartan
Subjects: QV pharmacology
Divisions: Faculty of Medicin > Department of Pathology
Depositing User: خدیجه شبانکاره
Date Deposited: 20 Dec 2020 09:24
Last Modified: 20 Dec 2020 09:24
URI: http://eprints.bpums.ac.ir/id/eprint/8999

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