The Protective Effect of Curcumin against Nitrosamine-Induced Gastric Oxidative Stress in Rats

Mostafa Ibrahim Waly,Ismail M. Al-Bulushi,Shaimaa Al-Hinai,Nejib Guizani,Raya Nasser Al-Malki,Mohammad Shafiur Rahman 한국식품영양과학회 2018 Preventive Nutrition and Food Science Vol.23 No.4

Curcumin has a wide spectrum of biological, pharmaceutical, and antioxidant effects in cancer experimental models. Nitrosamine is commonly used as an experimental oxidizing agent which induces gastric oxidative stress and gastric carcinogenesis in rats. We examined the antioxidant potential effect of curcumin against nitrosamine-induced gastric oxidative stress in rats. Forty Sprague-Dawley rats were randomly divided into 4 groups (10 rats/group). The control group was fed a standard diet and received a single dose of normal saline, the nitrosamine-treated group was fed a standard diet and received an intraperitoneal injection of nitrosamine at a single dose of 100 mg/kg body weight (b.w.). The other two groups received a daily dose of curcumin (200 mg/kg b.w.) via intra-gastric intubation in the presence or absence of nitrosamine injection. After 16 weeks, all rats were sacrificed, and the gastric tissues were dissected for histopathological examination and for biochemical measurements of oxidative stress indices. Our results showed that nitrosamine causes oxidative stress in gastric tissues as evidenced by glutathione depletion, increased level of lipid peroxides, nitric oxide release, impairment of total antioxidant capacity, DNA oxidative damage, and inhibition of antioxidant enzymes (catalase, glutathione peroxidase, glutathione reductase, and superoxide dismutase). Histopathological findings revealed abnormal gastric architecture in association with nitrosamine injection compared to the non-treated control group. Curcumin significantly suppressed the gastric oxidative damage associated with nitrosamine treatment and mitigated its histopathological effect. These results suggest that curcumin, as an antioxidant, has a therapeutic effect against oxidative stress-mediated gastric diseases.

낙동강 수계에서의 Nitrosamines 검출 현황

김경아(Gyung A Kim),손희종(Hee Jong Son),이상원(Sang Won Lee),류동춘(Dong Choon Ryu),권기원(Ki Won Kwon) 大韓環境工學會 2014 대한환경공학회지 Vol.36 No.1

본 연구에서는 낙동강에서의 nitrosamine류의 검출 현황에 대해 조사하였다. 본 연구결과에 따르면 6종의 nitrosamine류 (NDEA (N-nitrosodiethylamine), NDPA (N-Nitrosodi-n-propylamine), NDMA (N-nitrosodimethylamine), NMEA (N-nitrosomethylethylamine), NDBA (N-nitrosodi-n-butylamine) 및 NDPHA (N-Nitrosodiphenylamine))가 낙동강에서 검출되었다. 검출된 nitrosamine류 6종 중에서 NDEA와 NDPA가 주요 오염물질로 나타났으며, 몇몇 지점들에서의 NDEA의 검출농도는 미국 CDHCS (California Department of Health Care Services)의 대응수준인 100 ng/L를 초과하였으며, NDPA의 경우는 소수의 지점들에서 CDHCS의 대응수준(500 ng/L)에 근접한 농도로 검출되었다. 낙동강에서 검출된 nitrosamine류 9종의 최대 검출농도는 735.7ng/L로 나타났다. The survey of nitrosamine occurrence at Nakdong river is conducted in this study. According to the study results, six nitrosamine compounds (NDEA as N-nitrosodiethylamine, NDPA as N-Nitrosodi-n-propylamine, NDMA as N-nitrosodimethylamine, NMEA as N-nitrosomethylethylamine, NDBA as N-nitrosodi-n-butylamine, and NDPHA as N-Nitrosodiphenylamine) were detected at the Nakdong river. Among these, NDEA and NDPA are the most important compounds in terms of the nitrosamine contamination of Nakdong river. The detected concentration of NDEA exceeded the CDHCS (California Department of Health Care Services) response level of 100 ng/L at several sites. The detected concentration of NDPA approached the response level (500 ng/L) at few sites. When all nitrosamine concentrations were summed up, the maximum concentration of 735.7 ng/L was detected at the Nakdong river.

N-butyl-N(4-hydroxybutyl) Nitrosamine에 의한 흰쥐방광암 발생과정에서 E-cadherin과 Catenin의 발현

박용진,기승석,김남돈,김성곤,박언섭 중앙대학교 의과대학 의과학연구소 2003 中央醫大誌 Vol.28 No.2-3

Although urothelial cell carcinoma is the most common primary tumor of the urinary bladder, the mechanisms that regulate its development and progression remain unclear. β-catenin plays a fundamental role in the regulation of E-cadherin-catenin cell adhesion complex. Mutations in either β-catenin or E-cadherin gene result in up or down-regulation of protein expression. This study was conducted to evaluate the expression changes of β-catenin and E-cadherin protein during 0.05% BBN-induced rat bladder carcinogenesis. Spray-Dawley Rats were given 0.05% N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) by drinking water, and sacrificed at 5, 10, 20, and 30 weeks following treatment. For sequential changes and the expression of E-cadherin and β-catenin during rat bladder tumorigenesis, morphologic assesment and immunohistochemical staining were done. During the carcinogenesis, sequential histological changes from hyperplasia to papilloma, and ultimately overt carcinomas were noted. On histopathological findings, urothelial cell hyperplasias was appeared at 5 weeks, followed by urothelial papillomas at 10 weeks, and superficial urothelial carcinomas was found at 20 weeks after BBN administration. After 30 weeks of BBN administration, invasive carcinomas were developed. The immunohistochemical stains for E-cadherin and β-catenin displayed reduced expression in papilloma and carcinomas. Abnormal cytoplasmic expression of E-cadherin and β-catenin were observed in papillomas and carcinoms, especially in invasive carcinomas. In summary, the loss or reduced expression of E-cadherin and β-catenin are closely related with tumor propagation. Abnormal cytoplasmic expression of E-cadherin and β-catenin are late events favoring tumor progression in superficial type to invasive form in rat BBN-induced bladder cancer. The present study demonstrates that E-cadherin and β-catenin may play an important role in bladder carcinogenesis.

N-butyl-N-(4-hydroxybutyl) Nitrosamine으로 유발시킨 쥐의 방광암에서 Magnolia officinalis 추출물의 항암효과

이승찬,정필두,김용준,윤석중,이상철,김원재 대한비뇨의학회 2008 Investigative and Clinical Urology Vol.49 No.8

Purpose: Magnolia officinalis has been used in traditional Chinese medicine to treat a variety of diseases. The main constituents of Magnolia officinalis are honokiol and magnolol, which have a variety of pharmacological effects, such as antitumor, antioxidant, antimicrobial, anti-inflammatory etc. This study examined the anticancer effect of a Magnolia officinalis' extract on urinary bladder cancer in vivo. Materials and Methods: Male mice C3H/He were used as the experimental animals. The mice were divided into ten groups. Normal drinking water was provided to group 1(5 mice) for 20 weeks and 0.05% N-butyl- N-(4-hydroxybutyl) nitrosamine(BBN) was added to in the drinking water of group 2(5 mice). 0.1, 0.3, 1.0 and 3.0% Magnolia officinalis' extract was added to groups 3, 4, 5 and 6, respectively(5 mice each), and 0.1, 0.3, 1.0 and 3.0% Magnolia officinalis' extract plus 0.05% BBN was added to groups 7, 8, 9 and 10, respectively(10 mice each) for the same period. All surviving mice were sacrificed at week 20 to investigate the occurrence of bladder cancer, stage and grade. Results: Bladder cancer was not observed in groups 1, 3, 4, 5 and 6 mice. The rates of bladder cancer occurrence were 57.1, 66.7, 44.4 and 20.0% in groups 7, 8, 9 and 10, respectively. The incidence decreased with increasing concentration of Magnolia officinalis (p=0.005). However, the stage and grade were not associated with the concentration of Magnolia officinalis(each p>0.05). Conclusions: This study showed that Magnolia officinalis has some protective effect against bladder cancer. In the future, Magnolia officinalis may be expected to play an important role as a chemo-preventive and therapeutic agent or as a complementary agent in bladder cancer. Purpose: Magnolia officinalis has been used in traditional Chinese medicine to treat a variety of diseases. The main constituents of Magnolia officinalis are honokiol and magnolol, which have a variety of pharmacological effects, such as antitumor, antioxidant, antimicrobial, anti-inflammatory etc. This study examined the anticancer effect of a Magnolia officinalis' extract on urinary bladder cancer in vivo. Materials and Methods: Male mice C3H/He were used as the experimental animals. The mice were divided into ten groups. Normal drinking water was provided to group 1(5 mice) for 20 weeks and 0.05% N-butyl- N-(4-hydroxybutyl) nitrosamine(BBN) was added to in the drinking water of group 2(5 mice). 0.1, 0.3, 1.0 and 3.0% Magnolia officinalis' extract was added to groups 3, 4, 5 and 6, respectively(5 mice each), and 0.1, 0.3, 1.0 and 3.0% Magnolia officinalis' extract plus 0.05% BBN was added to groups 7, 8, 9 and 10, respectively(10 mice each) for the same period. All surviving mice were sacrificed at week 20 to investigate the occurrence of bladder cancer, stage and grade. Results: Bladder cancer was not observed in groups 1, 3, 4, 5 and 6 mice. The rates of bladder cancer occurrence were 57.1, 66.7, 44.4 and 20.0% in groups 7, 8, 9 and 10, respectively. The incidence decreased with increasing concentration of Magnolia officinalis (p=0.005). However, the stage and grade were not associated with the concentration of Magnolia officinalis(each p>0.05). Conclusions: This study showed that Magnolia officinalis has some protective effect against bladder cancer. In the future, Magnolia officinalis may be expected to play an important role as a chemo-preventive and therapeutic agent or as a complementary agent in bladder cancer.

N-butyl-N-(4-hydroxybutyl) nitrosamine에 의한 흰쥐 방광암 발생과정에서 c-erbB-2 종양단백, 증식성 핵항원(PCNA)과 Apoptosis의 평가

박원주 외 중앙대학교 의과대학 의학연구소 2005 中央醫大誌 Vol.30 No.1

c-erbB-2 is a proto-oncogene that closely related to the epidermal growth factor receptor and plays an important role in carcinogenesis. Apoptosis and cell proliferation play a major roles in chemical multistage carcinogenesis. This study analyzed the status of c-erbB-2, apoptosis, and proliferating cell nuclear antigen (PCNA) during N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) induced rat urinary bladder carcinogenesis. For sequential histopathological findings of urinary bladder, 0.05% BBN was administered to male rats in 30 weeks. To detect protein expressions of c-erbB-2 and PCNA, immunohistochemical stains were used. Also apoptosis identified morphologically and TdT-mediated dUTP-biotin nick end labeling (TUNEL) were used. On histopathological findings, urothelial cell hyperplasia was appeared at 5 weeks, followed by urothelial papilloma at 10 weeks, and superfical urothelial carcinoma was found at 20 weeks after BBN administration. After 30 weeks of BBN administration, invasive carcinoma was developed in 40% (4/10) among the all 10 cancer rats. The immunohistochemical stains for c-erbB-2 did not expressed in normal urinary bladder. Overexpression of c-erbB-2 were observed along the cell membrane in urothelial cell hyperplasia and papilloma. Reduced expression of c-erbB-2 were found in both superficial and invasive carcinomas. The PCNA and apoptotic labeling indices were very low in normal bladder epithelia. With the lesions progressed from urothelial cell hyperplasia to papilloma to urothelial carcinoma, the PCNA and apoptotic labeling indices significantly increased (P<0.01). There was no correlation between PCNA, apoptosis indices and c-erbB-2 expression. The present results indicate that c-erbB-2 may participates the early stage of carcinogenesis and hyperproliferative cells might be more susceptible to apoptosis. Also, the numbers of the PCNA and apoptosis could be useful markes for evaluating the risk of malignant transformation of transitional cell carcinoma of the urinary bladder.

해조류에 의한 발암성 니트로사민 생성인자 분해작용

박영범,박욱연 도립 강원전문대학 2000 道立 江原專門大學 論文集 Vol.3 No.-

Nitrite plays an important role in the formation of carcinogenic nitrosamine. In order to effectively inhibit the formation of carcinogenic nitrosamine in food and biological systems, scavenging of residual nitrite is necessary. In screening test of nitrite scavenging effect of seaweed, the methanol extracts from Phaeophyta was more effective on the nitrite scavenging than those from Rhodophyta and Chlorophyta. Among the brown algae family, Laminariaceae, E. cava and E. stolonifera that belong to genus Ecklonia showed a marked nitrite scavenging effect at pH 1.2 and 3.0. In order to separate the nitrite scavenger, methanol extract of E. stolonifera was divided into diethyl ether, ethyl acetate, chloroform and water extracts. The rates were especially high in ethyl acetate fraction as compared with other extract.

흰쥐에서 N-butyl-N-(4-hydroxybutyl) Nitrosamine에 의해 유발된 방광암에 대한 방광내 BCG주입의 효과

송희철,김상우,임정식 大韓泌尿器科學會 1998 Korean Journal of Urology Vol.39 No.2

Mitoquinol mesylate (MITOQ) attenuates diethyl nitrosamine-induced hepatocellular carcinoma through modulation of mitochondrial antioxidant defense systems

Adisa Rahmat Adetutu,Sulaimon Lateef Adegboyega,Okeke Ebele Geraldine,Ariyo Olubukola Christianah,Abdulkareem Fatimah B. 한국독성학회 2022 Toxicological Research Vol.38 No.3

Diethyl nitrosamine (DEN) induced cirrhosis-hepatocellular carcinoma (HCC) model associates cancer progression with oxidative stress and mitochondrial dysfunction. This study investigated the effects of mitoquinol mesylate (MitoQ), a mitochondrial- targeted antioxidant on DEN-induced oxidative damage in HCC Wistar rats. Fifty male Wistar rats were randomly divided into five groups. Healthy control, DEN, and MitoQ groups were orally administered exactly 10 mg/kg of distilled water, DEN, and MitoQ, respectively for 16 weeks. Animals in the MitoQ + DEN group were pre-treated with MitoQ for a week followed by co-administration of 10 mg/kg each of MitoQ and DEN. DEN + MitoQ group received DEN for 8 weeks, then co-administration of 10 mg/kg each of DEN and MitoQ till the end of 16th week. Survival index, tumour incidence, hematological profile, liver function indices, lipid profile, mitochondrial membrane composition, mitochondrial respiratory enzymes, and antioxidant defense status in both mitochondrial and post-mitochondrial fractions plus expression of antioxidant genes were assessed. In MitoQ + DEN and DEN + MitoQ groups, 80% survival occurred while tumour incidence decreased by 60% and 40% respectively, compared to the DEN-only treated group. Similarly, MitoQ-administered groups showed a significant (p < 0.05) decrease in the activities of liver function enzymes while hemoglobin concentration, red blood cell count, and packed cell volume were significantly elevated compared to the DEN-only treated group. Administration of MitoQ to the DEN-intoxicated groups successfully enhanced the activities of mitochondrial F1F0- ATPase and succinate dehydrogenase; and up-regulated the expression and activities of SOD2, CAT, and GPx1. Macroscopic and microscopic features indicated a reversal of DEN-induced hepatocellular degeneration in the MitoQ + DEN and DEN + MitoQ groups. These data revealed that MitoQ intervention attenuated DEN-induced oxidative stress through modulation of mitochondrial antioxidant defense systems and alleviated the burden of HCC as a chemotherapeutic agent.

N-butyl-N-(4-hydroxybutyl) Nitrosamine 투여 후 유발된 흰쥐 방광암에서 형질전환 성장인자-β1과 수용기 Ⅰ, Ⅱ, Ⅲ의 발현

류수방,오경진,권동득,오봉렬,김세연,최인선,최 찬 大韓泌尿器科學會 2003 Korean Journal of Urology Vol.44 No.6

N-butyl-N-(4-hydroxybutyl) Nitrosamine에 의한 흰쥐방광암 발생과정에서 E-cadherin과 Catenin의 발현

박용진,기승석,김남돈,김성곤,박언섭 중앙대학교 의과대학 의과학연구소 2003 中央醫大誌 Vol.28 No.2