Chemoprevention of bicyclol against hepatic preneoplastic lesions

Zhu, Bing; Liu, Geng Tao; Wu, Ruo Su; Strada, Samuel J.

doi:10.4161/cbt.5.12.3377

Cited by 12 publications

(14 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In that case, bicyclol reduced the Km values for denitrosation below the values of deethylation, which may be attributed to the induction of specific CYPs. According to these results on DEN metabolism, the chemopreventive CXB effect in the MRH model could be similar to that of bicyclol [21] , mediated mainly by the 2B1/2 isoform. Isoforms of the 1A, 2A, 2B and 2E CYP families share a broader overlap in substrate selectivity.…”

mentioning

confidence: 78%

“…The rate of DEN metabolism in control and CXB-treated rat hepatic microsomes was measured by the production of both a deethylation metabolite, acetaldehyde, and a denitrosation metabolite, nitrite, as previously described [12,14,21] . The enzymatic assay was performed in a final volume of 1 mL TMP buffer (50 mmol/L Tris-HCl, 10 mmol/L MgCl2, 150 mmol/L KCl, pH 7.0) containing 0.5 mg rat hepatic microsomal protein, 1.2 mmol/L NADPH and 50 mmol/L DEN.…”

Section: In Vitro Biotransformation Of Den By Rat Hepatic Microsomesmentioning

confidence: 99%

“…Onehundred microliter aliquots of supernatant were used for nitrite measurements using a specific colorimetric assay kit (Cayman Chemical Co., Ann Arbor, MI), according to the manufacturer's instructions. Acetaldehyde production was determined by HPLC in a Waters Liquid Chromatography model 600 using an Xterra C18 phase reverse column (3.9 mm × 150 mm), as previously described [21] . As a control for CYP2B1/2-specificity, these assays were carried out in the presence of 50 mmol/L SKF-525A.…”

Section: In Vitro Biotransformation Of Den By Rat Hepatic Microsomesmentioning

confidence: 99%

“…Other chemoprotectors have been shown to act in a similar way. For example, among their multiple effects, diallyl sulfide, indole-3-carbinol, d-limonene and bicyclol induced the enzymatic activity of several CYP isoforms, including CYP2B1/2 [21,26] . In particular, the effect of bicyclol on CYP2B1 was associated with an increase in the denitrosation rate of DEN [21] .…”

mentioning

confidence: 99%

“…For example, among their multiple effects, diallyl sulfide, indole-3-carbinol, d-limonene and bicyclol induced the enzymatic activity of several CYP isoforms, including CYP2B1/2 [21,26] . In particular, the effect of bicyclol on CYP2B1 was associated with an increase in the denitrosation rate of DEN [21] . In that case, bicyclol reduced the Km values for denitrosation below the values of deethylation, which may be attributed to the induction of specific CYPs.…”

mentioning

confidence: 99%

See 4 more Smart Citations

Celecoxib enhances the detoxification of diethylnitrosamine in rat liver cancer

Salcido-Neyoy¹,

Sierra-Santoyo²,

Beltrán-Ramírez³

et al. 2009

WJG

View full text Add to dashboard Cite

AIM:To study the effect of celecoxib (CXB) on diethylnitrosamine activation through the regulation of cytochrome P450 in a hepatocarcinogenesis model. METHODS:Six-week-old male Sprague-Dawley rats were randomly divided into five groups, a nontreated group (NT), a diethylnitrosamine-treated group (DEN), a DEN+CXB-treated group (DEN+CXB), and CXB 8 d-treated and CXB 32 d-treated groups. The effects of celecoxib on the enzymatic activities of CYP1A1, 2A, 2B1/2, and 2E1 were assessed in hepatic microsomes 24 h after DEN administration. Changes in CYP1A1 and CYP2B1/2 protein expression were also evaluated. The rate of DEN metabolism was measured by the production of the deethylation metabolite acetaldehyde, and the denitrosation metabolite nitrite.RESULTS: DEN+CXB administration produced a significant increase in the enzymatic activities of CYP2B1/2 and 1A1, whereas it did not change the activities of CYP2A and 2E1, compared to that of the DEN group. CXB treatment for eight days did not produce a significant effect on enzymatic activity when compared to the NT group; however, when it was administered for prolonged times (CXB 32 d group), the enzymatic activities were increased in a similar pattern to those in the DEN+CXB group. The observed increase in the enzymatic activities in the DEN+CXB group was accompanied by an increase in the CYP2B1/2 protein levels; no changes were observed in the levels of CYP1A1. In vitro , CXB increased the denitrosation of DEN, a pathway of metabolic detoxification. The addition of SKF-525A, a preferential inhibitor of CYP2B, abrogated the denitrosation of DEN. CONCLUSION:These results suggest that the mechanism of action of CXB involves enhancement of the detoxification of DEN by an increasing denitrosation via CYP2B1/2.

show abstract

mentioning

confidence: 78%

Section: In Vitro Biotransformation Of Den By Rat Hepatic Microsomesmentioning

confidence: 99%

Section: In Vitro Biotransformation Of Den By Rat Hepatic Microsomesmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Celecoxib enhances the detoxification of diethylnitrosamine in rat liver cancer

Salcido-Neyoy¹,

Sierra-Santoyo²,

Beltrán-Ramírez³

et al. 2009

WJG

View full text Add to dashboard Cite

show abstract

Chemoprevention of Hepatocellular Carcinoma in Chronic Hepatitis C

Morgan

2010

Clinical Cancer Prevention

View full text Add to dashboard Cite

Hepatitis C virus (HCV) infection causes chronic hepatitis, which can progress to cirrhosis and hepatocellular carcinoma (HCC). The incidence of hepatocellular carcinoma in the United States tripled between 1975 and 2005, and is expected to increase further, and to remain elevated for more than 20 years. Curing hepatitis C infection in patients with cirrhosis through treatment with peginterferon and ribavirin reduces the risk of developing hepatocellular carcinoma. Several noncurative treatments also appear to reduce the risk of hepatocellular carcinoma in patients with chronic hepatitis C. Prospective studies report a reduced incidence of hepatocellular carcinoma among patients treated with a mixture of carotenoids with or without myo-inositol, with vitamin K₂, or with polyprenoic acid (an acyclic retinoid). Uncontrolled and/or retrospective studies have reported beneficial effects of treatment with Sho-saiko-to, glycyrrhizin and ursodeoxycholic acid on hepatocellular carcinoma incidence. Meta-analyses of epidemiologic studies show a reduced risk of hepatocellular carcinoma among liver disease patients who drink two or more cups of coffee per day. Numerous agents prevent or reduce hepatocarcinogenesis in animal models. An ongoing Phase II clinical trial is evaluating S-adenosylmethionine (SAMe) as a potential chemopreventive agent in hepatitis C cirrhosis. Overall, these data suggest that chemoprevention of hepatocellular carcinoma in patients with chronic hepatitis C is an achievable objective.

show abstract