<span style="font-variant: small-caps">l</span>-Cysteine and <span style="font-variant: small-caps">l</span>-Serine Modified Dendrimer with Multiple Reduced Thiols as a Kidney-Targeting Reactive Oxygen Species Scavenger to Prevent Renal Ischemia/Reperfusion Injury
<span style="font-variant: small-caps;">l</span>-cysteine (Cys)- and <span style="font-variant: small-caps;">l</span>-serine (Ser)-modified, third-generation polyamidoamine (PAMAM) dendrimer with multiple reduced thiols (Ser-PAMAM-Cys) was synthesized as a...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2018-12-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/10/4/251 |
| _version_ | 1828371016006500352 |
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| author | Satoru Matsuura Hidemasa Katsumi Hiroe Suzuki Natsuko Hirai Rie Takashima Masaki Morishita Toshiyasu Sakane Akira Yamamoto |
| author_facet | Satoru Matsuura Hidemasa Katsumi Hiroe Suzuki Natsuko Hirai Rie Takashima Masaki Morishita Toshiyasu Sakane Akira Yamamoto |
| author_sort | Satoru Matsuura |
| collection | DOAJ |
| description | <span style="font-variant: small-caps;">l</span>-cysteine (Cys)- and <span style="font-variant: small-caps;">l</span>-serine (Ser)-modified, third-generation polyamidoamine (PAMAM) dendrimer with multiple reduced thiols (Ser-PAMAM-Cys) was synthesized as a kidney-targeting reactive oxygen species (ROS) scavenger to help prevent renal ischemia/reperfusion injury. Ser-PAMAM-Cys effectively scavenged 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical and ROS (hydrogen peroxide and hydroxyl radical) in phosphate-buffered saline (PBS). In addition, ~64% of <sup>111</sup>In-labeled Ser-PAMAM-Cys accumulated in mouse kidney 3 h after intravenous administration. An in vivo imaging system (IVIS) study indicated that near-infrared fluorescence dye (NIR)-labeled Ser-PAMAM-Cys specifically accumulated in the kidney. In a mouse renal ischemia/reperfusion injury model, increases in the kidney damage markers creatinine (Cre) and blood urea nitrogen (BUN) were significantly inhibited by intravenous Ser-PAMAM-Cys administration. In contrast, Cys injection had no statistically significant effect of preventing Cre or BUN elevation relative to the control. Ser-PAMAM-Cys also effectively downregulated the inflammatory factors NGAL, IL-18, ICAM-1, and VCAM-1 in the renal ischemia/reperfusion injury model. These results indicate that Ser-PAMAM-Cys is a promising kidney-targeting ROS scavenger which could prevent ischemia/reperfusion-induced renal failure. |
| first_indexed | 2024-04-14T06:45:24Z |
| format | Article |
| id | doaj.art-20cecb29c0eb46bd81d3c66890e68917 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-04-14T06:45:24Z |
| publishDate | 2018-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-20cecb29c0eb46bd81d3c66890e689172022-12-22T02:07:11ZengMDPI AGPharmaceutics1999-49232018-12-0110425110.3390/pharmaceutics10040251pharmaceutics10040251<span style="font-variant: small-caps">l</span>-Cysteine and <span style="font-variant: small-caps">l</span>-Serine Modified Dendrimer with Multiple Reduced Thiols as a Kidney-Targeting Reactive Oxygen Species Scavenger to Prevent Renal Ischemia/Reperfusion InjurySatoru Matsuura0Hidemasa Katsumi1Hiroe Suzuki2Natsuko Hirai3Rie Takashima4Masaki Morishita5Toshiyasu Sakane6Akira Yamamoto7Department of Biopharmaceutics, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8414, JapanDepartment of Biopharmaceutics, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8414, JapanDepartment of Biopharmaceutics, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8414, JapanDepartment of Biopharmaceutics, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8414, JapanDepartment of Biopharmaceutics, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8414, JapanDepartment of Biopharmaceutics, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8414, JapanDepartment of Biopharmaceutics, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8414, JapanDepartment of Biopharmaceutics, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8414, Japan<span style="font-variant: small-caps;">l</span>-cysteine (Cys)- and <span style="font-variant: small-caps;">l</span>-serine (Ser)-modified, third-generation polyamidoamine (PAMAM) dendrimer with multiple reduced thiols (Ser-PAMAM-Cys) was synthesized as a kidney-targeting reactive oxygen species (ROS) scavenger to help prevent renal ischemia/reperfusion injury. Ser-PAMAM-Cys effectively scavenged 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical and ROS (hydrogen peroxide and hydroxyl radical) in phosphate-buffered saline (PBS). In addition, ~64% of <sup>111</sup>In-labeled Ser-PAMAM-Cys accumulated in mouse kidney 3 h after intravenous administration. An in vivo imaging system (IVIS) study indicated that near-infrared fluorescence dye (NIR)-labeled Ser-PAMAM-Cys specifically accumulated in the kidney. In a mouse renal ischemia/reperfusion injury model, increases in the kidney damage markers creatinine (Cre) and blood urea nitrogen (BUN) were significantly inhibited by intravenous Ser-PAMAM-Cys administration. In contrast, Cys injection had no statistically significant effect of preventing Cre or BUN elevation relative to the control. Ser-PAMAM-Cys also effectively downregulated the inflammatory factors NGAL, IL-18, ICAM-1, and VCAM-1 in the renal ischemia/reperfusion injury model. These results indicate that Ser-PAMAM-Cys is a promising kidney-targeting ROS scavenger which could prevent ischemia/reperfusion-induced renal failure.https://www.mdpi.com/1999-4923/10/4/251dendrimerdrug deliveryrenal targetingkidneyamino acidreactive oxygen species scavengerischemia/reperfusion injury |
| spellingShingle | Satoru Matsuura Hidemasa Katsumi Hiroe Suzuki Natsuko Hirai Rie Takashima Masaki Morishita Toshiyasu Sakane Akira Yamamoto <span style="font-variant: small-caps">l</span>-Cysteine and <span style="font-variant: small-caps">l</span>-Serine Modified Dendrimer with Multiple Reduced Thiols as a Kidney-Targeting Reactive Oxygen Species Scavenger to Prevent Renal Ischemia/Reperfusion Injury Pharmaceutics dendrimer drug delivery renal targeting kidney amino acid reactive oxygen species scavenger ischemia/reperfusion injury |
| title | <span style="font-variant: small-caps">l</span>-Cysteine and <span style="font-variant: small-caps">l</span>-Serine Modified Dendrimer with Multiple Reduced Thiols as a Kidney-Targeting Reactive Oxygen Species Scavenger to Prevent Renal Ischemia/Reperfusion Injury |
| title_full | <span style="font-variant: small-caps">l</span>-Cysteine and <span style="font-variant: small-caps">l</span>-Serine Modified Dendrimer with Multiple Reduced Thiols as a Kidney-Targeting Reactive Oxygen Species Scavenger to Prevent Renal Ischemia/Reperfusion Injury |
| title_fullStr | <span style="font-variant: small-caps">l</span>-Cysteine and <span style="font-variant: small-caps">l</span>-Serine Modified Dendrimer with Multiple Reduced Thiols as a Kidney-Targeting Reactive Oxygen Species Scavenger to Prevent Renal Ischemia/Reperfusion Injury |
| title_full_unstemmed | <span style="font-variant: small-caps">l</span>-Cysteine and <span style="font-variant: small-caps">l</span>-Serine Modified Dendrimer with Multiple Reduced Thiols as a Kidney-Targeting Reactive Oxygen Species Scavenger to Prevent Renal Ischemia/Reperfusion Injury |
| title_short | <span style="font-variant: small-caps">l</span>-Cysteine and <span style="font-variant: small-caps">l</span>-Serine Modified Dendrimer with Multiple Reduced Thiols as a Kidney-Targeting Reactive Oxygen Species Scavenger to Prevent Renal Ischemia/Reperfusion Injury |
| title_sort | span style font variant small caps l span cysteine and span style font variant small caps l span serine modified dendrimer with multiple reduced thiols as a kidney targeting reactive oxygen species scavenger to prevent renal ischemia reperfusion injury |
| topic | dendrimer drug delivery renal targeting kidney amino acid reactive oxygen species scavenger ischemia/reperfusion injury |
| url | https://www.mdpi.com/1999-4923/10/4/251 |
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