Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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A Dunnione Compound MB12662 Improves Cisplatin-Induced Tissue Injury and Emesis

  • Park, Dongsun (College of Veterinary Medicine, Chungbuk National University) ;
  • Jo, In Geun (College of Pharmacy, Advanced Science, Dankook University) ;
  • Jang, Ja Young (College of Veterinary Medicine, Chungbuk National University) ;
  • Kwak, Tae Hwan (KT&G Life Science Corporation R&D Center) ;
  • Yoo, Sang Ku (Erum Biotechnologies Incorporation) ;
  • Jeon, Jeong Hee (College of Veterinary Medicine, Chungbuk National University) ;
  • Choi, Ehn-Kyoung (College of Veterinary Medicine, Chungbuk National University) ;
  • Joo, Seong Soo (Department of Marine Molecular Biotechnology, College of Life Science, Gangneung-Wonju National University) ;
  • Kim, Okjin (College of Natural Resources, Wonkwang University) ;
  • Kim, Yun-Bae (College of Veterinary Medicine, Chungbuk National University)
  • Received : 2015.03.25
  • Accepted : 2015.05.06
  • Published : 2015.09.01
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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.

Keywords

References

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