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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

Representative findings of the small intestine of mice orally administered with MB12662 for 10 days and intraperitoneally challenged with cisplatin (3.5 mg/kg) on days 4–7. (A) normal control; (B) cisplatin alone; (C), cisplatin + 10 mg/kg MB12662; (D) cisplatin + 50 mg/kg MB12662. Note the severe degeneration and atrophy of intestinal villi (arrow heads) and relatively-mild injury of crypts (asterisks) in B and C, in comparison with the normal features in A.
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f3-bt-23-449: Representative findings of the small intestine of mice orally administered with MB12662 for 10 days and intraperitoneally challenged with cisplatin (3.5 mg/kg) on days 4–7. (A) normal control; (B) cisplatin alone; (C), cisplatin + 10 mg/kg MB12662; (D) cisplatin + 50 mg/kg MB12662. Note the severe degeneration and atrophy of intestinal villi (arrow heads) and relatively-mild injury of crypts (asterisks) in B and C, in comparison with the normal features in A.

Mentions: Cisplatin induced degeneration and severe atrophy of small intestinal villi (Fig. 3B), compared to the normal features in control animals (Fig. 3A). In contrast, the effect of cisplatin on the crypts was not remarkable. MB12662 improved the intestinal injuries in a dose-dependent manner. Although low doses (5 – 10 mg/kg) of MB12662 were less effective (Fig. 3C), 25 mg/kg of MB12662 exhibited a marked protective efficacy. Especially, a full recovery of the villi degeneration and atrophy was achieved with 50 mg/kg of MB12662 (Fig. 3D).


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)

Representative findings of the small intestine of mice orally administered with MB12662 for 10 days and intraperitoneally challenged with cisplatin (3.5 mg/kg) on days 4–7. (A) normal control; (B) cisplatin alone; (C), cisplatin + 10 mg/kg MB12662; (D) cisplatin + 50 mg/kg MB12662. Note the severe degeneration and atrophy of intestinal villi (arrow heads) and relatively-mild injury of crypts (asterisks) in B and C, in comparison with the normal features in A.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f3-bt-23-449: Representative findings of the small intestine of mice orally administered with MB12662 for 10 days and intraperitoneally challenged with cisplatin (3.5 mg/kg) on days 4–7. (A) normal control; (B) cisplatin alone; (C), cisplatin + 10 mg/kg MB12662; (D) cisplatin + 50 mg/kg MB12662. Note the severe degeneration and atrophy of intestinal villi (arrow heads) and relatively-mild injury of crypts (asterisks) in B and C, in comparison with the normal features in A.
Mentions: Cisplatin induced degeneration and severe atrophy of small intestinal villi (Fig. 3B), compared to the normal features in control animals (Fig. 3A). In contrast, the effect of cisplatin on the crypts was not remarkable. MB12662 improved the intestinal injuries in a dose-dependent manner. Although low doses (5 – 10 mg/kg) of MB12662 were less effective (Fig. 3C), 25 mg/kg of MB12662 exhibited a marked protective efficacy. Especially, a full recovery of the villi degeneration and atrophy was achieved with 50 mg/kg of MB12662 (Fig. 3D).

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