Dietary lycopene attenuates cigarette smoke-promoted nonalcoholic steatohepatitis by preventing suppression of antioxidant enzymes in ferrets.
Dietary lycopene attenuates cigarette smoke-promoted nonalcoholic steatohepatitis by preventing suppression of antioxidant enzymes in ferrets.
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DOI：
10.1016/j.jnutbio.2021.108596
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发表时间：
2021-05
影响因子：
5.6
通讯作者：
Wang, Xiang-Dong
中科院分区：
文献类型：
--
作者：
Rakic, Jelena Mustra;Liu, Chun;Veeramachaneni, Sudipta;Wu, Dayong;Paul, Ligi;Ausman, Lynne M.;Wang, Xiang-Dong
吸烟（CS）是非酒精性脂肪性肝炎（NASH）和纤维化发展的独立危险因素。番茄红素是一种天然存在于番茄中的类胡萝卜素，已被证明是针对烟草致癌物4-（甲基亚硝胺基）-1-（3-吡啶基）-1-丁酮（NNK）诱导的NASH的保护剂。在本研究中，使用雪貂模型，我们调查了CS是否促进NASH和饮食番茄红素是否可以抑制CS促进NASH的发展，如果是这样，涉及哪些潜在的机制。将雪貂分为4组（n=12 - 16/组）：对照组、NNK/CS暴露组、NNK/CS加低剂量番茄红素（2.2 mg/kg BW/天）组和NNK/CS加高剂量番茄红素（6.6 mg/kg BW/天）组，持续26周。结果显示，与对照组相比，NNK/CS组的肝脂肪变性、炎性细胞浸润、肝脏中炎性病灶的数量和大小以及参与肝纤维化的关键基因更高;番茄红素饮食将这些变化逆转至对照组的水平。有趣的是，一种主要的番茄红素裂解酶，β-胡萝卜素9 '，10'-加氧酶（BCO 2），最近已被公认为发挥代谢作用以外的裂解功能，被下调NNK/CS曝光，但这种减少是防止番茄红素喂养。NNK/CS暴露还下调了肝脏抗氧化酶的表达，上调了氧化应激标志物，这些都被番茄红素阻止。总之，我们的研究结果表明，CS可以促进NASH和肝纤维化的发展，这是与下调的BCO 2和抗氧化系统在肝脏的损害;膳食番茄红素可以抑制CS促进NASH通过防止抑制BCO 2和抗氧化网络下降。
Cigarette smoke (CS) is an independent risk factor in development of nonalcoholic steatohepatitis (NASH) and fibrosis. Lycopene, a carotenoid naturally occurring in tomatoes, has been shown to be a protective agent against tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced NASH. In the present study using a ferret model we investigated whether CS promotes NASH and whether dietary lycopene can inhibit CS-promoted NASH development, and if so, what potential mechanisms were involved. Ferrets were divided into 4 groups (n=12−16/group): control, NNK/CS exposed, NNK/CS plus low-dose lycopene (2.2 mg/kg BW/day), and NNK/CS plus high-dose lycopene (6.6 mg/kg BW/day) groups, for 26 weeks. Results showed that hepatic steatosis, infiltrates of inflammatory cells, and the number and size of inflammatory foci in liver, together with key genes involved in hepatic fibrogenesis were higher in the NNK/CS group compared to the control group; a lycopene diet reversed these changes to the levels of the control group. Interestingly, a major lycopene cleavage enzyme, beta-carotene 9’,10’-oxygenase (BCO2), which recently has been recognized to play metabolic roles beyond cleavage function, was down-regulated by NNK/CS exposure, but this decrease was prevented by lycopene feeding. NNK/CS exposure also downregulated liver expression of antioxidant enzymes and upregulated oxidative stress marker, which were all prevented by lycopene. In conclusion, our results suggest that CS can promote development of NASH and liver fibrosis in ferrets, which is associated with downregulation of BCO2 and impairment of antioxidant system in liver; dietary lycopene may inhibit CS-promoted NASH by preventing suppression of BCO2 and decline in antioxidant network.
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DOI：
10.1158/1940-6207.capr-14-0154
发表时间：
2014-12
期刊：
Cancer prevention research (Philadelphia, Pa.)
影响因子：
--
作者：
Ip BC;Liu C;Ausman LM;von Lintig J;Wang XD
通讯作者：
Wang XD
影响因子：
13.5
作者：
Azzalini, Lorenzo;Ferrer, Elisabet;Bataller, Ramon
通讯作者：
Bataller, Ramon
影响因子：
4.8
作者：
Kiefer, C;Hessel, S;von Lintig, J
通讯作者：
von Lintig, J
影响因子：
5.2
作者：
Gong, Xiaoming;Marisiddaiah, Raju;Rubin, Lewis P.
通讯作者：
Rubin, Lewis P.
影响因子：
3.9
作者：
Lim, Ji Ye;Liu, Chun;Wang, Xiang-Dong
通讯作者：
Wang, Xiang-Dong