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Pregled bibliografske jedinice broj: 709642

Časopis

Autori: Kim, H.J.; Ravichandran, K.; Ozkok. A.; Wang. Q.; He, Z.; Jani, A.; Galešić Ljubanović, Danica; Douglas, I.S.; Edelstein, C.L.
Naslov: The water-soluble triptolide derivative PG490-88 protects against cisplatin-induced acute kidney injury
( The water-soluble triptolide derivative PG490-88 protects against cisplatin-induced acute kidney injury )
Izvornik: The Journal of pharmacology and experimental therapeutics (0022-3565) 349 (2014), 3; 518-525
Vrsta rada: članak
Ključne riječi: Triptolide derivative PG490-88; cisplatin-induced acute kidney injury
( Triptolide derivative PG490-88; cisplatin-induced acute kidney injury )
Sažetak:
Triptolide, a traditional Chinese medicine, has anti-inflammatory, antiproliferative, and proapoptotic properties. As interstitial inflammation and tubular apoptosis are features of cisplatin-induced acute kidney injury (AKI), we determined the effect of the water-soluble triptolide derivative 14-succinyl triptolide sodium salt (PG490-88) in a mouse model of cisplatin-induced AKI. PG490-88 resulted in a significant decrease in blood urea nitrogen (BUN), serum creatinine, and acute tubular necrosis (ATN) score, and a nonsignificant increase in tubular apoptosis score in AKI. The mitogen-activated protein kinase (MAPK) pathway is activated in AKI. On immunoblot analysis, phosphoextracellular signal-regulated kinase (p- ERK) was increased 3.6- fold in AKI and 2.0-fold inhibited by PG490-88. Phospho-c-Jun N-terminal kinase (p-JNK) was increased in AKI. PG490-88 resulted in a nonsignificant decrease in p-JNK. Phospho-p38 was not affected by cisplatin or PG490-88. MAPK phosphatase-1 (MKP-1) that negatively regulates MAPK signaling has not previously been studied in AKI. MKP-1 activity was not affected by cisplatin or PG490-88. Changes in p-ERK, p-JNK, and MKP-1 were confirmed on reverse protein phase analysis. The ERK inhibitor U0126 resulted in lower BUN and serum creatinine, suggesting a mechanistic role of ERK in AKI. The increase in interleukin-1α (IL- 1α), IL-1β, IL-6, CXCL1, and IL-33 in the kidney in AKI was unaffected by PG490-88. In summary, PG490-88 protects against AKI and ATN despite no decrease in tubular apoptosis. The protection of PG490-88 against AKI was associated with a decrease in p-ERK and was independent of MKP-1 and proinflammatory cytokines. In conclusion, PG490-88 protects against cisplatin-induced AKI possibly by decreasing p-ERK.
Projekt / tema: 198-0000000-3355
Izvorni jezik: eng
Rad je indeksiran u
bazama podataka:
Current Contents Connect (CCC)
MEDLINE
Scopus
SCI-EXP, SSCI i/ili A&HCI
Science Citation Index Expanded (SCI-EXP) (sastavni dio Web of Science Core Collectiona)
Kategorija: Znanstveni
Znanstvena područja:
Temeljne medicinske znanosti
URL Internet adrese: http://jpet.aspetjournals.org/content/349/3/518.long
http://jpet.aspetjournals.org/content/349/3/518
Broj citata:
Altmetric:
DOI: 10.1124/jpet.114.213769
URL cjelovitog teksta:
Google Scholar: The water-soluble triptolide derivative PG490-88 protects against cisplatin-induced acute kidney injury
Upisao u CROSBI: Danica Ljubanović (danica.ljubanovic@zg.t-com.hr), 10. Kol. 2014. u 11:57 sati



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