S-nitrosylated l-serine-modified dendrimer as a kidney-targeting nitric oxide donor for prevention of renal ischaemia/reperfusion injury. (1st December 2020)

• Record Type: Journal Article
• Authors: Katsumi, Hidemasa; Takashima, Rie; Suzuki, Hiroe; Hirai, Natsuko; Matsuura, Satoru; Kimura, Hiroyuki; Morishita, Masaki; Yamamoto, Akira
• Is Part Of: Free radical research. Volume 54:Number 11/12(2020)
• Page Start: 841
• Page End: 847
• Publication Date: 2020-12-01
• Subjects: Ischaemia reperfusion -- kidney-targeted delivery -- nitric oxide -- nitric oxide targeting; Free radicals (Chemistry) -- Periodicals; Antioxidants -- Periodicals; Vitamin C -- Periodicals; Vitamin E -- Periodicals; 541.224
• DOI: 10.1080/10715762.2019.1697437
• Languages: English
• ISSNs: 1071-5762

Abstract

Abstract: Nitric oxide (NO) deficiency is known to play a role in renal ischaemia/reperfusion injury; therefore, kidney-targeting NO donor is expected to prevent renal ischaemia/reperfusion injury. We therefore developed an S-nitrosylated L-serine-modified polyamidoamine dendrimer (SNO-Ser-PAMAM), in which multiple S-nitrosothiols (NO donors) were covalently bound to L-serine-modified dendrimer, as a kidney-targeting NO donor. In the pharmacokinetic study, approximately 76% of 111 In-SNO-Ser-PAMAM accumulated in the kidney after intravenous injection in mice. Furthermore, single photon emission computed tomography/computed tomography (SPECT/CT) imaging study showed that 111 In-SNO-Ser-PAMAM specifically accumulated in the renal cortex after intravenous injection. SNO-Ser-PAMAM gradually released NO over a day in plasma, indicating that SNO-Ser-PAMAM would show sustained release of NO in vivo . In a mouse model of renal ischaemia/reperfusion injury, increased plasma creatinine, a kidney damage marker, and histological changes were effectively inhibited by intravenous administration of SNO-Ser-PAMAM. These results indicate that SNO-Ser-PAMAM is a promising kidney-targeting NO donor for the efficient prevention of renal ischaemia/reperfusion injury.