Lutein mitigates cyclophosphamide induced lung and liver injury via NF-κB/MAPK dependent mechanism

被引:50
作者
El-Kholy, Amal A. [1 ,2 ]
Elkablawy, Mohamed A. [3 ,4 ]
El-Agamy, Dina S. [5 ,6 ]
机构
[1] Taibah Univ, Fac Pharm, Dept Clin & Hosp Pharm, Al Madinah Al Munawwarah 30001, Saudi Arabia
[2] Ain Shams Univ, Fac Pharm, Dept Clin Pharm, Cairo 11566, Egypt
[3] Taibah Univ, Fac Med, Dept Pathol, Al Madinah Al Munawwarah 30001, Saudi Arabia
[4] Menoufia Univ, Fac Med, Dept Pathol, Menoufia 32511, Egypt
[5] Taibah Univ, Coll Pharm, Dept Pharmacol & Toxicol, Al Madinah Al Munawwarah 30001, Saudi Arabia
[6] Mansoura Univ, Fac Pharm, Dept Pharmacol & Toxicol, Mansoura 35516, Egypt
关键词
Lutein; Cyclophosphamide; Pulmonary injury; Hepatotoxicity; NF-kappa beta; MAPK; INDUCED OXIDATIVE STRESS; HEMORRHAGIC CYSTITIS; INDUCED HEPATOTOXICITY; INDUCED CARDIOTOXICITY; DIALLYL DISULFIDE; DNA-DAMAGE; MICE; RATS; GENOTOXICITY; INFLAMMATION;
D O I
10.1016/j.biopha.2017.05.103
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
This study targeted to test the potential protective role of lutein against lung and liver damage associated with cyclophosphamide (CP) administration. Lutein was given orally for 5 days at two different doses both before and after CP injection. Results have shown that CP administration caused marked pulmonary and hepatic injurious effects in mice. Lung damage was evident through increased lung wet/dry ratio, elevated inflammatory cells infiltration into the pulmonary tissues, increased total protein content and lactate dehydrogenase (LDH) activity in the broncho-alveolar lavage fluid. Estimation of high levels of serum transaminases, alkaline phosphatase and LDH in serum revealed hepatic injury. Histopathological examination of both organs confirmed the biochemical analysis. Elevation of oxidative stress along with depressed anti-oxidant status of lung and liver were evident in CP-intoxicated animals. Furthermore, CP induced elevation of inflammatory cytokines (NOx, TNF-alpha, IL-6) contaminant with activation of nuclear factor kappa-B (NF-kappa B) and p38 mitogen activated protein kinase (p38-MAPK). On the other side, lutein treatment successfully protected the lung and the liver as indicated by improvement of the biochemical and histopathological parameters. These results suggest that lutein can ameliorate CP-induced pulmonary and hepatic oxidative injurious effects via inhibition of reactive oxygen species (ROS)/NFkB/MAPK pathway. (C) 2017 Elsevier Masson SAS. All rights reserved.
引用
收藏
页码:519 / 527
页数:9
相关论文
共 55 条
[11]   Modulation of cyclophosphamide-induced cardiotoxicity by methyl palmitate [J].
El-Agamy, Dina S. ;
Elkablawy, Mohamed A. ;
Abo-Haded, Hany M. .
CANCER CHEMOTHERAPY AND PHARMACOLOGY, 2017, 79 (02) :399-409
[12]  
Gao SS, 2011, MOL VIS, V17, P3180
[13]  
GHOSH P, 2014, PHARM BIOL, V4, P1
[14]   Protective effects of blueberries (Vaccinium corymbosum L.) extract against cadmium-induced hepatotoxicity in mice [J].
Gong, Pin ;
Chen, Fu-xin ;
Wang, Lan ;
Wang, Jing ;
Jin, Sai ;
Ma, Yang-min .
ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY, 2014, 37 (03) :1015-1027
[15]   Lutein Prevents High Fat Diet-Induced Atherosclerosis in ApoE-Deficient Mice by Inhibiting NADPH Oxidase and Increasing PPAR Expression [J].
Han, Hao ;
Cui, Wei ;
Wang, Linzhi ;
Xiong, Yufang ;
Liu, Liegang ;
Sun, Xiufa ;
Hao, Liping .
LIPIDS, 2015, 50 (03) :261-273
[16]   Aqueous extract of walnut (Juglans regia L.) protects mice against cyclophosphamide induced biochemical toxicity [J].
Haque, R ;
Bin-Hafeez, B ;
Parvez, S ;
Pandey, S ;
Sayeed, I ;
Ali, M ;
Raisuddin, S .
HUMAN & EXPERIMENTAL TOXICOLOGY, 2003, 22 (09) :473-480
[17]   Mitogen activated protein (MAP) kinase signal transduction pathways and novel anti-inflammatory targets [J].
Hommes, DW ;
Peppelenbosch, MP ;
van Deventer, SJH .
GUT, 2003, 52 (01) :144-151
[18]   Protective effect of curcumin in cisplatin-induced oxidative injury in rat testis: mitogen-activated protein kinase and nuclear factor-kappa B signaling pathways [J].
Ilbey, Yusuf Ozlem ;
Ozbek, Emin ;
Cekmen, Mustafa ;
Simsek, Abdulmuttalip ;
Otunctemur, Alper ;
Somay, Adnan .
HUMAN REPRODUCTION, 2009, 24 (07) :1717-1725
[19]   Inhibitory effects of lutein on endotoxin-induced uveitis in Lewis rats [J].
Jin, Xue-Hai ;
Ohgami, Kazubiro ;
Shiratori, Kenji ;
Suzuki, Yukari ;
Hirano, Takeshi ;
Koyama, Yoshikazu ;
Yoshida, Kazubiko ;
Ilieva, Iliyana ;
Iseki, Ken ;
Ohno, Shigeaki .
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2006, 47 (06) :2562-2568
[20]   Phellinus linteus inhibits inflammatory mediators by suppressing redox-based NF-κB and MAPKs activation in lipopolysaccharide-induced RAW 264.7 macrophage [J].
Kim, Ho Gyoung ;
Yoon, Deok Hyo ;
Lee, Won Ho ;
Han, Sang Kuk ;
Shrestha, Bhushan ;
Kim, Chun Hoi ;
Lim, Mi Hee ;
Chang, Woochul ;
Lim, Soyeon ;
Choi, Sunga ;
Song, Won O. ;
Sung, Jae Mo ;
Hwang, Ki Chul ;
Kim, Tae Woong .
JOURNAL OF ETHNOPHARMACOLOGY, 2007, 114 (03) :307-315