Cardiotrophin-1 therapy prevents gentamicin-induced nephrotoxicity in rats
Aminoglycosides are very effective antibiotics for the treatment of severe infections, but they rank among the most frequent causes of drug-induced nephrotoxicity. Thus, prevention of aminoglycoside nephrotoxicity is an unmet therapeutic objective. Cardiotrophin-1 (CT-1), a member of the IL-6 family of cytokines, has been reported to protect the kidney against toxic and ischemic acute kidney injury (AKI). We have assessed the effect of rat CT-1 in the severity of gentamicin (G)-induced AKI. Groups of male Wistar rats received the following for 6 consecutive days: i) isotonic saline solution (group CONT), ii) G, 150mg/kg/day, i.p. (group G), iii) CT-1, 100μg/kg/day i.v. (group CT-1), or iv) G and CT-1 at the doses described above. The G group showed a manifest AKI characterized by low creatinine clearance, high plasma creatinine and urea levels, increased urinary excretion of proteins, glucose and AKI markers such as N-acetyl-glucosaminidase, neutrophil gelatinase-associated lipocalin, kidney-injury molecule-1 and T-gelsolin, increased kidney levels of CD-68, iNOS, IL-1β and TNF-α, and markedly higher histological renal damage and leukocyte infiltration than the CONT and CT-1 groups. Administration of CT-1 together with G reduced almost all of the above-described manifestations of G-induced AKI. The results of this study have potential clinical application, as CT-1 is near to being used as a drug for organ protection..
| Medienart: |
Artikel |
|---|
| Erscheinungsjahr: |
2016 |
|---|---|
| Erschienen: |
2016 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:107 |
|---|---|
| Enthalten in: |
Pharmacological research - 107(2016), Seite 137-146 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Quirós, Yaremi [VerfasserIn] |
|---|
| Links: |
|---|
| doi: |
10.1016/j.phrs.2016.02.025 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
OLC1974870529 |
|---|
| LEADER | 01000caa a2200265 4500 | ||
|---|---|---|---|
| 001 | OLC1974870529 | ||
| 003 | DE-627 | ||
| 005 | 20230714190821.0 | ||
| 007 | tu | ||
| 008 | 160609s2016 xx ||||| 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.phrs.2016.02.025 |2 doi | |
| 028 | 5 | 2 | |a PQ20160610 |
| 035 | |a (DE-627)OLC1974870529 | ||
| 035 | |a (DE-599)GBVOLC1974870529 | ||
| 035 | |a (PRQ)c1250-583f62feef3c9c96b58fb900d905981f86d55797d99705311d2308719fa3afc0 | ||
| 035 | |a (KEY)0039864020160000107000000137cardiotrophin1therapypreventsgentamicininducedneph | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 082 | 0 | 4 | |a 610 |q DNB |
| 084 | |a PHARM |2 fid | ||
| 100 | 1 | |a Quirós, Yaremi |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Cardiotrophin-1 therapy prevents gentamicin-induced nephrotoxicity in rats |
| 264 | 1 | |c 2016 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ohne Hilfsmittel zu benutzen |b n |2 rdamedia | ||
| 338 | |a Band |b nc |2 rdacarrier | ||
| 520 | |a Aminoglycosides are very effective antibiotics for the treatment of severe infections, but they rank among the most frequent causes of drug-induced nephrotoxicity. Thus, prevention of aminoglycoside nephrotoxicity is an unmet therapeutic objective. Cardiotrophin-1 (CT-1), a member of the IL-6 family of cytokines, has been reported to protect the kidney against toxic and ischemic acute kidney injury (AKI). We have assessed the effect of rat CT-1 in the severity of gentamicin (G)-induced AKI. Groups of male Wistar rats received the following for 6 consecutive days: i) isotonic saline solution (group CONT), ii) G, 150mg/kg/day, i.p. (group G), iii) CT-1, 100μg/kg/day i.v. (group CT-1), or iv) G and CT-1 at the doses described above. The G group showed a manifest AKI characterized by low creatinine clearance, high plasma creatinine and urea levels, increased urinary excretion of proteins, glucose and AKI markers such as N-acetyl-glucosaminidase, neutrophil gelatinase-associated lipocalin, kidney-injury molecule-1 and T-gelsolin, increased kidney levels of CD-68, iNOS, IL-1β and TNF-α, and markedly higher histological renal damage and leukocyte infiltration than the CONT and CT-1 groups. Administration of CT-1 together with G reduced almost all of the above-described manifestations of G-induced AKI. The results of this study have potential clinical application, as CT-1 is near to being used as a drug for organ protection. | ||
| 540 | |a Nutzungsrecht: © Elsevier Ltd | ||
| 540 | |a Copyright © 2016 Elsevier Ltd. All rights reserved. | ||
| 700 | 1 | |a Blanco-Gozalo, Victor |4 oth | |
| 700 | 1 | |a Sanchez-Gallego, Jose I |4 oth | |
| 700 | 1 | |a López-Hernandez, Francisco J |4 oth | |
| 700 | 1 | |a Ruiz, Juan |4 oth | |
| 700 | 1 | |a Perez de Obanos, María P |4 oth | |
| 700 | 1 | |a López-Novoa, José M |4 oth | |
| 773 | 0 | 8 | |i Enthalten in |t Pharmacological research |d Oxford [u.a.] : Elsevier, 1989 |g 107(2016), Seite 137-146 |w (DE-627)130776777 |w (DE-600)1003347-6 |w (DE-576)023037164 |x 1043-6618 |7 nnns |
| 773 | 1 | 8 | |g volume:107 |g year:2016 |g pages:137-146 |
| 856 | 4 | 1 | |u http://dx.doi.org/10.1016/j.phrs.2016.02.025 |3 Volltext |
| 856 | 4 | 2 | |u http://www.sciencedirect.com/science/article/pii/S1043661816301566 |
| 856 | 4 | 2 | |u http://www.ncbi.nlm.nih.gov/pubmed/26996880 |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a SYSFLAG_A | ||
| 912 | |a GBV_OLC | ||
| 912 | |a FID-PHARM | ||
| 912 | |a SSG-OLC-PHA | ||
| 912 | |a SSG-OLC-DE-84 | ||
| 912 | |a SSG-OPC-PHA | ||
| 912 | |a GBV_ILN_4219 | ||
| 951 | |a AR | ||
| 952 | |d 107 |j 2016 |h 137-146 | ||