Ulmus macrocarpa Hance Reduces Cyclophosphamide-induced Toxicity in Mouse Liver

국문 초록 (Abstract)

Cyclophosphamide (CP)는 면역 억제제 뿐만 아니라 암 및 림프종 등의 치료에 널리 사용된다. CP는 DNA 알킬화제로서, 간세포에서 대사되어 4-hydrocyclophosphamide (4H-CYP)와 aldophosphamide로 분리된다. Ulmus macrocarpa Hance는 부종, 유방염, 종양 및 기타 염증성 질환에 사용되어 왔다. 이 연구의 목적은 CP의 부작용에 대하여 U. macrocarpa Hance 열수 추출물이 조직학적 수준에서 CP의 부작용에 대한 간과 신장의 보호 기능과 U. macrocarpa Hance 자체의 잠재적 독성 영향을 조사하고자 하였다. 마우스 모델을 사용하여 헤마톡실린 및 에오신(H&E) 염색과 DAPI 염색으로 간과 신장을 조직학적으로 분석하였다. CP 처리한 마우스에서 간세포의 형태는 글리코겐 축적을 나타내지 않았고, 세포 밀도도 감소하였다. 그러나 UMWE+CP 처리군에서는 간세포의 형태와 세포 밀도는 정상 간세포 패턴과 유사하였다. 또한, UMWE으로만 처리한 마우스에서도 간세포의 형태와 세포밀도는 정상 간세포와 유사했다. 신장의 경우에는 정상 마우스와 비교했을 때 H&E 염색으로는 CP 또는 UMWE 처리된 마우스의 신장에서 명백한 차이를 나타내지 않았다. 즉, U. macrocarpa Hance의 열수추출물은 간과 신장에 아무런 영향을 유발하지 않으면서 CP가 유발한 독성을 감소시키는것으로 요약된다. 따라서 U. macrocarpa Hance는 제약 산업에 사용될 수 있는 가능성을 나타내었다.

다국어 초록 (Multilingual Abstract)

Cyclophosphamide (CP) is widely used in cancer and lymphoma treatments and as an immunosup-pressant drug. CP is a DNA alkylating agent that metabolizes into 4-hydrocyclophosphamide (4H-CYP) and aldophosphamide in hepatocytes. However, its metabolites cause DNA synthesis disorder, leading to apoptosis and toxic side effects. The development of technology to minimize this side effect is essential to improve CP’s clinical application. Various bioactive compounds have been reported to have anti-cancer and antioxidant functions and preventive or therapeutic roles in metabolic diseases. Many researchers have attempted to minimize the side effects and improve the efficacy of these drugs together with the use of bioactive compounds. Ulmus macrocarpa Hance has been used for the treatment of edema, mastitis, stomach pain, tumors, cystitis, and other inflammatory diseases. The aim of this study was to investigate at the histological level the protective function of U. macrocarpa Hance against CP’s side effects and any potential toxic effect of U. macrocarpa Hance in the liver and kidney. Water extracts of U. macrocarpa Hance reduced CP-induced toxicity and did not induce any histological damage in the liver and kidney. Therefore, U. macrocarpa Hance would be applicable in the pharmaceutical industry.

목차 (Table of Contents)

• Introduction
• Materials and Methods
• Results and Discussion
• References
• 초록

참고문헌 (Reference)

1 정경태, "왕느릅나무 추출물에 의한 비장세포 생존률 및 NK cell 세포독성 증가" 한국생명과학회 26 (26): 109-116, 2016

2 Sellers, R. S., "Society of toxicologic pathology position paper : organ weight recommendations for toxicology studies" 35 : 751-755, 2007

3 He, H. F., "Research progress on theaflavins : efficacy, formation, and preparation" 3 : 1344521-, 2017

4 El-Shabrawy, M., "Protective effect of tolvaptan against cyclophosphamide-induced nephrotoxicity in rat models" 8 : e00659-, 2020

5 Santos, M. L. C., "Nephrotoxicity in cancer treatment : An overview" 11 : 190-204, 2020

6 Iqubal, A., "Molecular mechanism involved in cyclophosphamide-induced cardiotoxicity : Old drug with a new vision" 218 : 112-131, 2019

7 Dutta, S., "Men and mice : Relating their ages" 152 : 244-248, 2016

8 Bhullar, K. S., "Lifespan and healthspan extension by resveratrol" 1852 : 1209-1218, 2015

9 Seo, B. I., "Illustrated Book of Herbal Plants in Oriental Medicine" DaeWondang 2011

10 Aladaileh, S. H., "Galangin activates Nrf2 signaling and attenuates oxidative damage, inflammation, and apoptosis in a rat model of cyclophosphamide-induced hepatotoxicity" 9 : 346-, 2019

11 Chan, P. C., "Fourteen-week toxicity study of green tea extract in rats and mice" 38 : 1070-1084, 2010

12 Yang, W. K., "Extract of Ulmus macrocarpa Hance prevents thrombus formation through antiplatelet activity" 8 : 726-730, 2013

13 Michael, B., "Evaluation of organ weights for rodent and non-rodent toxicity studies : a review of regulatory guidelines and a survey of current practices" 35 : 742-750, 2007

14 김태명, "Elm tree bark extract inhibits HepG2 hepatic cancer cell growth via pro-apoptotic activity" 대한수의학회 13 (13): 7-13, 2012

15 Kim, J. M., "Effect of Euonymus alatus and Ulmus clavidiana var japonica on the immune system" 34 : 307-313, 1994

16 Khajavi, R. A., "Druginduced nephrotoxicity and medicinal plants" 11 : 169-179, 2017

17 De la Iglesia, R., "Dietary strategies implicated in the prevention and treatment of metabolic syndrome" 17 : 1877-, 2016

18 Üsküdar, C. D., "Cyclophosphamide-induced severe acute hepatitis in a rheumatic disease : case-based review" 39 : 377-385, 2019

19 Oyagbemi, A. A., "Cyclophosphamide-induced hepatotoxicity in wistar rats : the modulatory role of gallic acid as a hepatoprotective and chemopreventive phytochemical" 7 : 51-, 2016

20 Almazor, M. E. S., "Cyclophosphamide for rheumatoid arthritis" 4 : CD001157-, 2000

21 Griffin, B. R., "Biomarkers of drug-induced kidney toxicity" 41 : 213-226, 2019

22 Skrovankova, S., "Bioactive compounds and antioxidant activity in different types of berries" 16 : 24673-24706, 2015

23 Subramaniam, S., "Bioactive compounds : natural defense against cancer?" 9 : 758-, 2019

24 Xia, N., "Antioxidant effects of resveratrol in the cardiovascular system" 174 : 1633-1646, 2017

25 Oh, K. S., "Antihypertensive, vasorelaxant, and antioxidant effect of root bark of Ulmus macrocarpa" 31 : 2090-2096, 2008

26 Ohishi, T., "Anti-inflammatory action of green tea" 15 : 74-90, 2016

27 Hoffman, W. P., "Analysis of rodent growth data in toxicology studies" 66 : 313-319, 2002

28 Marunaka, Y., "Actions of quercetin, a polyphenol, on blood pressure" 22 : 209-, 2017