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A Dunnione Compound MB12662 Improves Cisplatin-Induced Tissue Injury and Emesis
- Source :
- Biomolecules & Therapeutics
- Publication Year :
- 2015
- Publisher :
- The Korean Society of Applied Pharmacology, 2015.
-
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.
- Subjects :
- Pathology
medicine.medical_specialty
Pharmacology
Biochemistry
Nephrotoxicity
Immune system
Atrophy
Drug Discovery
medicine
Splenocyte
Retching
Cisplatin
business.industry
MB12662
Emesis
medicine.disease
medicine.anatomical_structure
Intestinal injury
Vomiting
Molecular Medicine
Original Article
Dunnione
Bone marrow
medicine.symptom
business
medicine.drug
Subjects
Details
- ISSN :
- 19769148 and 20054483
- Volume :
- 23
- Database :
- OpenAIRE
- Journal :
- Biomolecules & Therapeutics
- Accession number :
- edsair.doi.dedup.....b567b3e9a8871557bafe61f098ae306d