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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.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.

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 intraperitoneally administered with cisplatin 4 times on days 1–4. ○, normal control; ▼, 3.5 mg/kg cisplatin; ■, 5 mg/kg cisplatin; ◆, 6.5 mg/kg cisplatin.
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f1-bt-23-449: Change in the body weights of mice intraperitoneally administered with cisplatin 4 times on days 1–4. ○, normal control; ▼, 3.5 mg/kg cisplatin; ■, 5 mg/kg cisplatin; ◆, 6.5 mg/kg cisplatin.

Mentions: The treatment period of cisplatin was set at 4 days according to a clinical anti-cancer therapeutic schedule, and its dose inducing intestinal injury without mortality was considered as an optimal dosage. The body weights of male mice intraperitoneally challenged with 3.5 mg/kg of cisplatin for 4 days gradually decreased, reaching a nadir of 15.1% loss on day 7 (3 days after the final administration), and then recovered to a similar level on day 12 to that before treatment (Fig. 1). However, the body weight did not further increase to the level of normal animals. The mice challenged with 5 mg/kg of cisplatin showed abrupt body weight loss after the 2nd administration reaching 68.5% of control on day 7, resulting in mortality of 16.7% and 50% on days 8 and 19, respectively. The animals treated with a high dose (6.5 mg/kg) of cisplatin displayed 35% loss of body weights. At this dosage, 33.3% of the mice exhibited bloody diarrhea, and 16.7%, 33.3%, 83.3% and 100% of the animals died on days 7, 8, 9 and 10.


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 intraperitoneally administered with cisplatin 4 times on days 1–4. ○, normal control; ▼, 3.5 mg/kg cisplatin; ■, 5 mg/kg cisplatin; ◆, 6.5 mg/kg cisplatin.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f1-bt-23-449: Change in the body weights of mice intraperitoneally administered with cisplatin 4 times on days 1–4. ○, normal control; ▼, 3.5 mg/kg cisplatin; ■, 5 mg/kg cisplatin; ◆, 6.5 mg/kg cisplatin.
Mentions: The treatment period of cisplatin was set at 4 days according to a clinical anti-cancer therapeutic schedule, and its dose inducing intestinal injury without mortality was considered as an optimal dosage. The body weights of male mice intraperitoneally challenged with 3.5 mg/kg of cisplatin for 4 days gradually decreased, reaching a nadir of 15.1% loss on day 7 (3 days after the final administration), and then recovered to a similar level on day 12 to that before treatment (Fig. 1). However, the body weight did not further increase to the level of normal animals. The mice challenged with 5 mg/kg of cisplatin showed abrupt body weight loss after the 2nd administration reaching 68.5% of control on day 7, resulting in mortality of 16.7% and 50% on days 8 and 19, respectively. The animals treated with a high dose (6.5 mg/kg) of cisplatin displayed 35% loss of body weights. At this dosage, 33.3% of the mice exhibited bloody diarrhea, and 16.7%, 33.3%, 83.3% and 100% of the animals died on days 7, 8, 9 and 10.

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.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.

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