A Dunnione Compound MB12662 Improves Cisplatin-Induced Tissue Injury and Emesis.
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.
College of Veterinary Medicine, Chungbuk National University, Cheongju 362-763 ; Department of Physiology, Ajou University School of Medicine, Suwon 443-749, Republic of Korea.
Dongsun
D
Park
College of Pharmacy, Advanced Science, Dankook University, Cheonan 330-714.
In Geun
IG
Jo
College of Veterinary Medicine, Chungbuk National University, Cheongju 362-763.
Ja Young
JY
Jang
KT&G Life Science Corporation R&D Center, Suwon 443-702.
Tae Hwan
TH
Kwak
Erum Biotechnologies Incorporation, Suwon 443-380.
Sang Ku
SK
Yoo
College of Veterinary Medicine, Chungbuk National University, Cheongju 362-763.
Jeong Hee
JH
Jeon
College of Veterinary Medicine, Chungbuk National University, Cheongju 362-763.
Ehn-Kyoung
EK
Choi
Department of Marine Molecular Biotechnology, College of Life Science, Gangneung-Wonju National University, Gangneung 210-702.
Seong Soo
SS
Joo
College of Natural Resources, Wonkwang University, Iksan 570-749.
Okjin
O
Kim
College of Veterinary Medicine, Chungbuk National University, Cheongju 362-763.
Yun-Bae
YB
Kim
Cisplatin; Dunnione; Emesis; Intestinal injury; MB12662; Nephrotoxicity