A Dunnione Compound MB12662 Improves Cisplatin-Induced Tissue Injury and Emesis.
10.4062/biomolther.2015.034
- Author:
Dongsun PARK
1
;
In Geun JO
;
Ja Young JANG
;
Tae Hwan KWAK
;
Sang Ku YOO
;
Jeong Hee JEON
;
Ehn Kyoung CHOI
;
Seong Soo JOO
;
Okjin KIM
;
Yun Bae KIM
Author Information
1. College of Veterinary Medicine, Chungbuk National University, Cheongju 362-763, Republic of Korea. solar93@cbu.ac.kr
- Publication Type:Original Article
- Keywords:
Cisplatin;
Emesis;
Intestinal injury;
Nephrotoxicity;
Dunnione;
MB12662
- MeSH:
Animals;
Atrophy;
Body Weight;
Bone Marrow;
Cisplatin;
Ferrets;
Humans;
Immune System;
Male;
Mice;
Mice, Inbred ICR;
Mortality;
Reflex;
Stem Cells;
Vomiting*
- From:Biomolecules & Therapeutics
2015;23(5):449-457
- CountryRepublic of Korea
- Language:English
-
Abstract:
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.
