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

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.

Effect of seven oriental herbs mixture (Jogyeongbohyeoldan) on the restoration of ovarian aging in aged mice

“…Cisplatin is a first-line chemotherapeutic agent for ovarian cancer that has been widely used to establish POF model. The mice that received 2.0 mg/kg cisplatin showed abrupt body weight loss on the 2 day and decreased locomotor activity from day 5 [63], and the numbers of primordial and preovulatory follicles in the ovary were significantly decreased at day 10 [64]. For this reason, many studies have injected 2 mg/kg cisplatin intraperitoneally daily for 10 days [65,66].…”