Details

Autor(en) / Beteiligte

• Park, Dongsun
• Jo, In Geun
• Jang, Ja Young
• Kwak, Tae Hwan
• Yoo, Sang Ku
• Jeon, Jeong Hee
• Choi, Ehn-Kyoung
• Joo, Seong Soo
• Kim, Okjin
• Kim, Yun-Bae

Titel

A Dunnione Compound MB12662 Improves Cisplatin-Induced Tissue Injury and Emesis

Ist Teil von

• Biomolecules & therapeutics, 2015-09, Vol.23 (5), p.449-457

Ort / Verlag

한국응용약물학회

Erscheinungsjahr

2015

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• The present study was aimed to investigate the effects of MB12662, a synthetic dunnione compound, on cisplatin-induced vomiting reflexes and intestinal, renal, immune system, and hematopoietic toxicities in ferrets and mice, respectively. Male ICR mice were orally administered MB12662 (5, 10, 25 or 50 mg/kg) for 10 days, during which intraperitoneally challenged with cisplatin (3.5 mg/kg) from day 4 to 7, and sacrificed on day 10 for the pathological examination. Male ferrets were orally administered MB12662 (25, 50 or 100 mg/kg) for 7 days, subcutaneously challenged with cisplatin (5 mg/kg), and monitored for vomiting reflexes and survival of the animals. Four-day injection of cisplatin (3.5 mg/kg) to mice caused body weight loss and degeneration and atrophy of intestinal villi, reducing villi/crypt ratio to a half level of control animals. Cisplatin also induced renal and hepatic toxicities, and depletion of splenocytes and bone marrow progenitor cells. The systemic toxicities including decreased villi/crypt ratio, immune system atrophy, splenocyte depletion, and decreased cellularity in bone marrow were improved by MB12662. Cisplatin (5 mg/kg) induced retching and emetic responses of ferrets, which were remarkably attenuated by MB12662 in a dose-dependent manner. All the ferrets pretreated with MB12662 survived the challenge of cisplatin, in comparison with 40% mortality in vehicle-treated animals, and blood parameters of nephrotoxicity and hepatotoxicity were markedly recovered. It is expected that MB12662 could be a candidate for the body protection against burden, including emesis, of chemotherapeutic agents.