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

Park D, Jo IG, Jang JY, Kwak TH, Yoo SK, Jeon JH, Choi EK, Joo SS, Kim O, Kim YB - Biomol Ther (Seoul) (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: College of Veterinary Medicine, Chungbuk National University, Cheongju 362-763 ; Department of Physiology, Ajou University School of Medicine, Suwon 443-749, Republic of Korea.

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.

No MeSH data available.


Related in: MedlinePlus

Change in the body weights of mice orally administered with MB12662 for 10 days and intraperitoneally challenged with cisplatin (3.5 mg/kg) on days 4–7. ○, normal control; ●, cisplatin alone; ▼, cisplatin + 5 mg/kg MB12662; ■, cisplatin + 10 mg/kg MB12662; ◆, cisplatin + 25 mg/kg MB12662; ▲ cisplatin + 50 mg/kg MB12662.
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f2-bt-23-449: Change in the body weights of mice orally administered with MB12662 for 10 days and intraperitoneally challenged with cisplatin (3.5 mg/kg) on days 4–7. ○, normal control; ●, cisplatin alone; ▼, cisplatin + 5 mg/kg MB12662; ■, cisplatin + 10 mg/kg MB12662; ◆, cisplatin + 25 mg/kg MB12662; ▲ cisplatin + 50 mg/kg MB12662.

Mentions: The body weights of vehicle-treated mice challenged with 3.5 mg/kg of cisplatin decreased by 23.9% on day 10 (3 days after the final challenge with cisplatin) (Fig. 2). Since the body weights of normal animals increased by 11.6% from 24.17 g to 26.97 g for 10 days, the real body weight loss in cisplatin-challenged mice from the weight of control animals was 31.8%. In comparison, treatment with MB12662 (10–50 mg/kg) tended to increase the body weights, resulting in higher weights, by 1.8–3 g, at the terminal day.


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

Park D, Jo IG, Jang JY, Kwak TH, Yoo SK, Jeon JH, Choi EK, Joo SS, Kim O, Kim YB - Biomol Ther (Seoul) (2015)

Change in the body weights of mice orally administered with MB12662 for 10 days and intraperitoneally challenged with cisplatin (3.5 mg/kg) on days 4–7. ○, normal control; ●, cisplatin alone; ▼, cisplatin + 5 mg/kg MB12662; ■, cisplatin + 10 mg/kg MB12662; ◆, cisplatin + 25 mg/kg MB12662; ▲ cisplatin + 50 mg/kg MB12662.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4556205&req=5

f2-bt-23-449: Change in the body weights of mice orally administered with MB12662 for 10 days and intraperitoneally challenged with cisplatin (3.5 mg/kg) on days 4–7. ○, normal control; ●, cisplatin alone; ▼, cisplatin + 5 mg/kg MB12662; ■, cisplatin + 10 mg/kg MB12662; ◆, cisplatin + 25 mg/kg MB12662; ▲ cisplatin + 50 mg/kg MB12662.
Mentions: The body weights of vehicle-treated mice challenged with 3.5 mg/kg of cisplatin decreased by 23.9% on day 10 (3 days after the final challenge with cisplatin) (Fig. 2). Since the body weights of normal animals increased by 11.6% from 24.17 g to 26.97 g for 10 days, the real body weight loss in cisplatin-challenged mice from the weight of control animals was 31.8%. In comparison, treatment with MB12662 (10–50 mg/kg) tended to increase the body weights, resulting in higher weights, by 1.8–3 g, at the terminal day.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: College of Veterinary Medicine, Chungbuk National University, Cheongju 362-763 ; Department of Physiology, Ajou University School of Medicine, Suwon 443-749, Republic of Korea.

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.

No MeSH data available.


Related in: MedlinePlus