Resveratrol Downregulates Cyp2e1 and Attenuates Chemically Induced Hepatocarcinogenesis in SD Rats

Wu, Xin; Li, Chenggang; Xing, Guozhen; Qi, Xinming; Ren, Jin

doi:10.1293/tox.2013-0020

Cited by 18 publications

(15 citation statements)

References 35 publications

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“…Further, an in vivo study in mice has demonstrated that RSV reduced the activity of CYP2E1 (Upadhyay et al, ). Moreover, a previous study reported by Wu et al () supports our study in which RSV reduced the CYP2E1 activity in rats. Furthermore, a previous study in healthy volunteers supported our study results where disulfiram (Frye and Branch, ) and diallyl sulphide (Loizou and Cocker, ) substantially reduced the metabolism of CHZ, and the observed effects are most likely the result of inhibition of CYP2E1.…”

Section: Discussionsupporting

confidence: 92%

Resveratrol Pretreatment Affects CYP2E1 Activity of Chlorzoxazone in Healthy Human Volunteers

Bedada

Prasad

2015

Phytotherapy Research

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The purpose of the present study was to investigate the effect of resveratrol (RSV) pretreatment on CYP2E1 enzyme activity and pharmacokinetics of chlorzoxazone (CHZ) in healthy human volunteers. The open-label, two period, sequential study was conducted in 12 healthy human volunteers. A single dose of RSV 500 mg was administered once daily for 10 days during treatment phase. A single dose of CHZ 250 mg was administered during control and after treatment phases under fasting conditions. The blood samples were collected after CHZ dosing at predetermined time intervals and analyzed by HPLC. RSV pretreatment significantly enhanced the maximum plasma concentration (Cmax), area under the curve (AUC) and half life (T1/2) and significantly decreased elimination rate constant (Kel), apparent oral clearance (CL/F) and apparent volume of distribution (Vd/F) of CHZ as compared to that of control. In addition, RSV pretreatment significantly decreased the metabolite to parent (6-OHCHZ/CHZ) ratios of Cmax, AUC and T1/2 and significantly increased the Kel ratio of 6-OHCHZ/CHZ, which indicated the reduced formation of CHZ to 6-OHCHZ. The results suggest that the altered CYP2E1 enzyme activity and pharmacokinetics of CHZ might be attributed to RSV mediated inhibition of CYP2E1 enzyme. Thus, there is a potential pharmacokinetic interaction between RSV and CHZ. The inhibition of CYP2E1 by RSV may provide a novel approach for minimizing the hepatotoxicity of ethanol.

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Section: Discussionsupporting

confidence: 92%

Resveratrol Pretreatment Affects CYP2E1 Activity of Chlorzoxazone in Healthy Human Volunteers

Bedada

Prasad

2015

Phytotherapy Research

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“…Cd-metallothionein complex is stored in the liver (28). When the total amount of Cd in the liver exceeds the binding capability of metallothionein, the non-metallothionein-bound Cd ions can induce oxidative stress that, in turn, can cause damage to these tissues (28).…”

Section: Discussionmentioning

confidence: 99%

Mitigating Effect of Resveratrol on the Structural Changes of Mice Liver and Kidney Induced by Cadmium; A Stereological Study

Rafati¹,

Hoseini²,

Babai³

et al. 2015

JFN

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Exposure to cadmium (Cd) has harmful effects on the liver and kidney. Resveratrol (RES) is an herbal substance that functions as a protective mediator. This study aimed to investigate the effects of RES on the histology of liver and kidney in Cd-exposed mice. Male mice were divided into 4 groups daily receiving normal saline (1 mL normal saline/d), Cd (1 mg/kg/d), RES (20 mg/kg/d), and Cd plus RES, respectively. After 4 weeks, the liver and kidney components were evaluated using stereological methods. The total volume and number of hepatocytes, and volume of fibrous tissue were respectively increased by 34%, 58%, and a 3-fold in the Cd-exposed mice in comparison to the control animals (P＜0.03). On the other hand, the volume of the main vasculature (sinusoids and central veins) was decreased by 36% in the Cd group compared to the control mice (P＜0.03). Considering the kidney, the results showed a 3-fold increase in the total glomeruli volume and a 7-fold increase in fibrous tissue in the Cd-treated group compared to the control mice (P＜0.03). After Cd treatment, a 32% reduction was observed in the volume and length of the proximal and distal convoluted tubules. RES-treatment alone did not induce any structural changes. In comparison to the Cd group, an increase in the normal components of the liver and kidney and a decrease in the formation of the fibrous and degenerated tissues were observed in the Cd+RES-treated mice (P＜0.03).

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“…Desoxyrhapontigenin may be useful in the modulation of the tumor microenvironment. It inhibits cytochrome P450 enzymes [378,379], inflammation, ROS, and associated pathways [380–385]. …”

Section: Approachesmentioning

confidence: 99%

Cancer prevention and therapy through the modulation of the tumor microenvironment

Casey

Amedei

Aquilano

et al. 2015

Seminars in Cancer Biology

304

204

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Cancer arises in the context of an in vivo tumor microenvironment. This microenvironment is both a cause and consequence of tumorigenesis. Tumor and host cells co-evolve dynamically through indirect and direct cellular interactions, eliciting multiscale effects on many biological programs, including cellular proliferation, growth, and metabolism, as well as angiogenesis and hypoxia and innate and adapative immunity. Here we highlight specific biological processes that could be exploited as targets for the prevention and therapy of cancer. Specifically, we describe how inhibition of targets such as cholesterol synthesis and metabolites, reactive oxygen species and hypoxia, macrophage activation and conversion, indoleamine 2, 3-dioxygenase regulation of dendritic cells, vascular endothelial growth factor regulation of angiogenesis, fibrosis inhibition, endoglin, and Janus kinase signaling emerge as examples of important potential nexuses in the regulation of tumorigenesis and the tumor microenvironment that can be targeted. We have also identified therapeutic agents as approaches, in particular natural products such as berberine, resveratrol, onionin A, epigallocatechin gallate, genistein, curcumin, naringenin, desoxyrhapontigenin, piperine, and zerumbone, that may warrant further investigation to target the tumor microenvironment for the treatment and/or prevention of cancer.

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Resveratrol Downregulates Cyp2e1 and Attenuates Chemically Induced Hepatocarcinogenesis in SD Rats

Cited by 18 publications

References 35 publications

Resveratrol Pretreatment Affects CYP2E1 Activity of Chlorzoxazone in Healthy Human Volunteers

Resveratrol Pretreatment Affects CYP2E1 Activity of Chlorzoxazone in Healthy Human Volunteers

Mitigating Effect of Resveratrol on the Structural Changes of Mice Liver and Kidney Induced by Cadmium; A Stereological Study

Cancer prevention and therapy through the modulation of the tumor microenvironment

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