Stimulation of Diethylnitrosamine Metabolism Reduces Its General Toxic and Hepatocarcinogenic Effects

Ilnitskaya, S. I.; Каледин, В. И.; Bogdanova, L. A.; Morozkova, T. S.; Kapustina, V. I.; Perepechaeva, M. L.; Grishanova, A. Yu.

doi:10.1007/s10517-016-3555-3

Cited by 3 publications

(1 citation statement)

References 5 publications

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“…The biotransformation of DEN by the cytochrome P450–dependent pathway produces active metabolites, which are primarily responsible for the initiation of hepatocarcinogenesis 27 . However, the electrophilic intermediates can be eliminated by making conjugates with hydrophilic molecules such as glutathione and glucuronic acid 28 .…”

Section: Discussionmentioning

confidence: 99%

Protocatechuic acid as a potent anticarcinogenic compound in purple rice bran against diethylnitrosamine-initiated rat hepatocarcinogenesis

Punvittayagul

Luangsuphabool

Wongpoomchai

2022

Sci Rep

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Our previous study demonstrated that purple rice bran extract (PRBE) could inhibit diethylnitrosamine (DEN)-induced hepatocarcinogenesis. Protocatechuic acid (PCA) is the major phenolic acid contained in the PRBE. Therefore, this study aimed to determine whether PCA is an anticarcinogenic compound in purple rice extract. Rats were intraperitoneally injected with DEN to induce glutathione S-transferase placental form (GST-P)-positive foci. Rats were fed with PRBE at 500 mg kg−1 body weight or PCA at 4 mg kg−1 body weight for 5 and 15 weeks. PCA administration attenuated DEN-induced hepatic GST-P positive foci to a degree similar to PRBE. The molecular mechanisms of PCA in the initiation stage were correlated with reduced activity of cytochrome P450 reductase and induction of glutathione S-transferase. In addition, PCA also downregulated the expression of TNF-α and IL-1β genes in rat liver. These genes are associated with the inhibition of inflammation. In the promotion stage, PCA suppressed cell proliferation correlated with the downregulation of Cyclin D1 expression. Moreover, it also induced apoptosis, indicated by increased expression of P53 and Bad genes, and decreased the expression of the anti-apoptotic Bcl-xl in DEN-initiated rats. These findings suggest that PCA is an active compound in the anticarcinogenic action of purple rice bran.

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Section: Discussionmentioning

confidence: 99%

Protocatechuic acid as a potent anticarcinogenic compound in purple rice bran against diethylnitrosamine-initiated rat hepatocarcinogenesis

Punvittayagul

Luangsuphabool

Wongpoomchai

2022

Sci Rep

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Off-target lipid metabolism disruption by the mouse constitutive androstane receptor ligand TCPOBOP in humanized mice

Skoda

Dohnalová

Chalupský

et al. 2022

Biochemical Pharmacology

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Inhibitory effect of chlormethiazole on the toxicokinetics of diethylnitrosamine in normal and hepatofibrotic rats

Wang

Wan

Gao

et al. 2018

Drug and Chemical Toxicology

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The effect of chlormethiazole (CMZ) at single and multiple doses on the toxicokinetics of diethylnitrosamine (DEN) was investigated in normal rats and those with DEN-induced liver fibrosis. Twelve rats were treated with DEN (50 mg/kg) alone and in combination with a single dose of CMZ (10, 50, or 100 mg/kg) by intraperitoneal (i.p.) injection. In a multiple dose test, six rats were treated with CMZ (50 mg/kg) for 7 d with addition of DEN (50 mg/kg) on days 1 and 7. Lastly, 12 rats were treated with DEN (50 mg/kg) by i.p. injection twice a week for 4 consecutive weeks, followed by weekly injections for another 8 weeks to build the model of liver fibrosis. Following this induction, the 12 rats were given CMZ (50 mg/kg) combined with DEN (50 mg/kg) to study the inhibitory effect of CMZ on DEN metabolism in hepatofibrotic rats. Serial blood samples were also collected and analyzed by a validated high-performance liquid chromatography (HPLC) method. A single-dose CMZ treatment decreased DEN clearance (CL), prolonged the t, and increased the 'area under the curve' (AUC) for DEN in normal and hepatofibrotic rats relative to rats that did not receive CMZ. Treatment with CMZ for 7 d further prolonged the t for DEN but did not alter the CL and AUC relative to a single CMZ treatment. These results suggest that CMZ significantly inhibits the metabolism of DEN in normal and hepatofibrotic rats.

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Stimulation of Diethylnitrosamine Metabolism Reduces Its General Toxic and Hepatocarcinogenic Effects

Cited by 3 publications

References 5 publications

Protocatechuic acid as a potent anticarcinogenic compound in purple rice bran against diethylnitrosamine-initiated rat hepatocarcinogenesis

Protocatechuic acid as a potent anticarcinogenic compound in purple rice bran against diethylnitrosamine-initiated rat hepatocarcinogenesis

Off-target lipid metabolism disruption by the mouse constitutive androstane receptor ligand TCPOBOP in humanized mice

Inhibitory effect of chlormethiazole on the toxicokinetics of diethylnitrosamine in normal and hepatofibrotic rats

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