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A Dunnione Compound MB12662 Improves Cisplatin-Induced Tissue Injury and Emesis
( Dongsun Park ),( In Geun Jo ),( Ja Young Jang ),( Tae Hwan Kwak ),( Sang Ku Yoo ),( Jeong Hee Jeon ),( Ehn-kyoung Choi ),( Seong Soo Joo ),( Okjin Kim ),( Yun-bae Kim ) 한국응용약물학회 2015 Biomolecules & Therapeutics(구 응용약물학회지) Vol.23 No.5
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.
A Dunnione Compound MB12662 Improves Cisplatin-Induced Tissue Injury and Emesis
Park, Dongsun,Jo, In Geun,Jang, Ja Young,Kwak, Tae Hwan,Yoo, Sang Ku,Jeon, Jeong Hee,Choi, Ehn-Kyoung,Joo, Seong Soo,Kim, Okjin,Kim, Yun-Bae The Korean Society of Applied Pharmacology 2015 Biomolecules & Therapeutics(구 응용약물학회지) Vol.23 No.5
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.
Dongsun Park,Jangbeen Kyung,Dajeong Kim,Seock-Yeon Hwang,Ehn-Kyoung Choi,Yun-Bae Kim 한국실험동물학회 2012 Laboratory Animal Research Vol.28 No.1
The effects of polarized-light therapy (PLT) on high-cholesterol diet (HCD)-induced hypercholesterolemia and atherosclerosis were investigated in comparison with that of lovastatin in rabbits. Hypercholesterolemia was induced by feeding male New Zealand white rabbits with 1% cholesterol in diet for 2 weeks and maintained with 0.5% cholesterol for 6 weeks, followed by normal diet for 2 weeks for recovery. Lovastatin (0.002% in diet) or daily 5-min or 20-min PLT on the outside surface of ears was started 2 weeks after induction of hypercholesterolemia. Hypercholesterolemic rabbits exhibited great increases in serum cholesterol and low-density lipoproteins (LDL) levels, and finally severe atheromatous plaques formation covering 57.5% of the arterial walls. Lovastatin markedly reduced both the cholesterol and LDL, but the reducing effect (47.5%) on atheroma formation was relatively low. By comparison, 5-min PLT preferentially decreased LDL, rather than cholesterol, and thereby potentially reduced the atheroma area to 42.2%. Notably, 20-min PLT was superior to lovastatin in reducing both the cholesterol and LDL levels as well as the atheromatous plaque formation (26.4%). In contrast to the increases in blood alanine transaminase and aspartate transaminase following lovastatin treatment, PLT did not cause hepatotoxicity. In addition, PLT decreased platelets and hematocrit level. The results indicate that PLT attenuates atherosclerosis not only by lowering blood cholesterol and LDL levels, but also by improving blood flow without adverse effects. Therefore, it is suggested that PLT could be a safe alternative therapy for the improvement of hypercholesterolemia and atherosclerosis.
Preventive effect of piperonyl butoxide on cyclophosphamide-induced teratogenesis in rats
Park, Dongsun,Kim, Sunghyun,Kang, Hyomin,Oh, Jiyoung,Jang, Ja Young,Shin, Sunhee,Kim, Tae Kyun,Choi, Young Jin,Lee, Sun Hee,Kim, Ki-Yon,Joo, Seong Soo,Kim, Yun-Bae Wiley Subscription Services, Inc., A Wiley Company 2009 Birth defects research. Part B, Developmental and Vol.86 No.5
<P>BACKGROUND: Cyclophosphamide induces fetal defects through metabolic activation by cytochrome P-450 monooxygenases (CYP). The effects of piperonyl butoxide (PBO), a CYP inhibitor, on the fetal development and external, visceral, and skeletal abnormalities induced by cyclophosphamide were investigated in rats. METHODS: Pregnant rats were daily administered PBO (400 mg/kg) by gavage for 7 days (the 6th to 12th day of gestation), and intraperitoneally administered with cyclophosphamide (12 mg/kg) 4 h after the final treatment. On the 20th day of gestation, maternal and fetal abnormalities were determined by Cesarean section. RESULTS: Cyclophosphamide reduced fetal body weights by 30–40% without increasing resorption or death. In addition, it induced malformations in live fetuses: 100, 98, and 98.2% of the external (head and limb defects), visceral (cerebroventricular dilatation, cleft palate, and renal pelvic/ureteric dilatation), and skeletal (acrania, vertebral/costal malformations, and delayed ossification) abnormalities, respectively. The pre-treatment of PBO greatly decreased mRNA expression and activity of hepatic CYP2B, which metabolizes cyclophosphamide into teratogenic acrolein and cytotoxic phosphoramide mustard. Moreover, PBO remarkably attenuated cyclophosphamide-induced body weight loss and abnormalities of fetuses; score 3.57 versus 1.87 for exencephaly, 75.5% versus 42.5% for limb defects, 65.3% versus 22% for cerebroventricular dilatation, 59.2% versus 5.1% for cleft palate, score 1.28 versus 0.93 for renal pelvic/ureteric dilatation, 71.9–82.5% versus 23–45.9% for vertebral/costal malformations, and 84.2% versus 57.4% for delayed ossification in cyclophosphamide alone and PBO co-administration groups. CONCLUSIONS: These results suggest that repeated treatment with PBO may improve cyclophosphamide-induced body weight loss and malformations of fetuses by down-regulating CYP2B. Birth Defects Res (Part B) 86:402–408, 2009. © 2009 Wiley-Liss, Inc.</P>
Park, Dongsun,Joo, Seong Soo,Kim, Tae Kyun,Lee, Sun Hee,Kang, Hyomin,Lee, Hong Jun,Lim, Inja,Matsuo, Akinori,Tooyama, Ikuo,Kim, Yun-Bae,Kim, Seung U Pergamon Press ; Elsevier Science Ltd ; Elsevier S 2012 Cell transplantation Vol.21 No.1
<P>Alzheimer disease (AD) is a progressive neurodegenerative disease, which is characterized by loss of memory and cognitive function. In AD patients dysfunction of the cholinergic system is the main cause of cognitive disorders, and decreased activity of choline acetyltransferase (ChAT), an enzyme responsible for acetylcholine (ACh) synthesis, is observed. In the present study we investigated if brain transplantation of human neural stem cells (NSCs) genetically modified to encode ChAT gene improves cognitive function of kainic acid (KA)-induced learning deficit rats. Intrahippocampal injection of KA to hippocampal CA3 region caused severe neuronal loss, resulting in profound learning and memory deficit. F3.ChAT human NSCs transplanted intracerebroventricularly improved fully the learning and memory function of KA-induced learning deficit animals, in parallel with the elevation of ACh levels in cerebrospinal fluid. F3.ChAT human NSCs migrated to the KA-induced injury site (CA3) and differentiated into neurons and astrocytes. The present study demonstrates that human NSCs expressing ChAT have lesion-tropic property and improve cognitive function of learning deficit model rats with hippocampal injury by increasing ACh level.</P>
Augmentation by Hypercholesterolemia of Amyloid β Peptide-Induced Learning and Memory Deficit
Dongsun Park, Jiyoung Oh, Tae Kyun Kim, Young Jin Cho, Sun Hee Lee, Dae-Kwon Bae, Yun-Hui Yang, Goeun Yang, Seock-Yeon Hwang, Yun-Bae Kim 충북대학교 동물의학연구소 2009 Journal of Biomedical and Translational Research Vol.10 No.2
본문참고
Antioxidative and Antidiarrheal Effects of Persimmon Extracts
Dongsun Park,Sun Hee Lee,Dae-Kwon Bae,Young Jin Choi,Tea Kyun Kim,Yun-Hui Yang,Goeun Yang,Sang-Chul Kwon,Do Ik Lee,Sung Soo Joo,Yun-Bae Kim 한국실험동물학회 2010 Laboratory Animal Research Vol.26 No.4
Since oxidative stresses are involved in gastroenteritis and diarrhea, we investigated antioxidative and antidiarrheal activities of persimmon flesh extract (PFE) and persimmon calyx extract (PCE) in vitro and in vivo, respectively. PCE significantly scavenged 1,1-diphenyl-2-picrylhydrazyl hydrate and 2,2'-azinobis (3-ethylbenzthiazoline-6-sulfonic acid) from 500 ㎍/mL, although PFE was ineffective. In addition, PFE and PCE exhibited strong nitric oxide-scavenging effects from 1 μg/mL, in which PCE was superior to ascorbic acid (50 μM). Furthermore, PFE and PCE significantly inhibited FeCl3-induced lipid peroxidation as well as Cu<SUP>2+</SUP>/H₂O₂-induced protein oxidation from 10 μg/mL. In vivo charcoal-propulsion assay, in contrast to a negligible effect of PFE, treatment with PCE (160-500 ㎎/㎏) markedly inhibited intestinal motility. The results indicate that extracts of persimmon, especially PCE, possess antioxidative, antiinflammatory and antidiarrheal activities. Therefore, it is suggested that persimmon extracts could be used for the relief of gastroenteritis and diarrhea.