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Pregled bibliografske jedinice broj: 709642

The water-soluble triptolide derivative PG490-88 protects against cisplatin-induced acute kidney injury


Kim, H.J.; Ravichandran, K.; Ozkok. A.; Wang. Q.; He, Z.; Jani, A.; Galešić Ljubanović, Danica; Douglas, I.S.; Edelstein, C.L.
The water-soluble triptolide derivative PG490-88 protects against cisplatin-induced acute kidney injury // The Journal of pharmacology and experimental therapeutics, 349 (2014), 3; 518-525 doi:10.1124/jpet.114.213769 (međunarodna recenzija, članak, znanstveni)


Naslov
The water-soluble triptolide derivative PG490-88 protects against cisplatin-induced acute kidney injury

Autori
Kim, H.J. ; Ravichandran, K. ; Ozkok. A. ; Wang. Q. ; He, Z. ; Jani, A. ; Galešić Ljubanović, Danica ; Douglas, I.S. ; Edelstein, C.L.

Izvornik
The Journal of pharmacology and experimental therapeutics (0022-3565) 349 (2014), 3; 518-525

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
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.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti



POVEZANOST RADA


Projekt / tema
198-0000000-3355 - Značaj morfoloških čimbenika u dijagnostici, terapiji i prognozi FSGS (Danica Galešić-Ljubanović, )

Ustanove
Medicinski fakultet, Zagreb,
Klinička bolnica "Dubrava"

Autor s matičnim brojem:
Danica Galešić-Ljubanović, (203674)

Časopis indeksira:


  • Current Contents Connect (CCC)
  • Web of Science Core Collection (WoSCC)
    • Science Citation Index Expanded (SCI-EXP)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus
  • MEDLINE


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