Indole-3-carbinol enhances oxidative stress responses resulting in the induction of preneoplastic liver cell lesions in partially hepatectomized rats initiated with diethylnitrosamine

Shimamoto, Keisuke; Dewa, Yasuaki; Ishii, Yuji; Kemmochi, Sayaka; Taniai, Eriko; Hayashi, Hitomi; Imaoka, Masako; Morita, Rimpei; Kuwata, Kazunori; Suzuki, Kazuhiko; Shibutani, Makoto; Mitsumori, Kunitoshi

doi:10.1016/j.tox.2011.03.003

Cited by 27 publications

(25 citation statements)

References 52 publications

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“…These disturbances in liver function may be as a result of the metastasis of tumor cells to the liver and the change in redox status [40]. Keisuke, reported that, a redox imbalance' subsequently induces liver tumor-promoting effects by enhancing cellular proliferation in rats [9]. Cancer cells exhibit increased glycolysis in combination with a reduced rate of respiration [41] [42].…”

Section: Discussionmentioning

confidence: 99%

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Suppression Effect of Superoxide Dismutase (SOD)-Like Activity Protein Partially Purified from <i>Raphnus sativus</i> Leaves against Liver Metastasis in Mice Intraperitoneally Infected with Ehrlich Ascites Carcinoma Cell

Toson¹,

Almutairi²,

Elfalal³

et al. 2016

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Liver metastasis is a normal result in Ehrlich Ascites Carcinoma Cell (EAC) infected mice. A partially purified protein with Superoxide Dismutase (SOD)-like activity extracted from leaves of Raphnus sativus was tested for its ability to down regulate liver metastasis of Ehrlich Ascites Carcinoma Cell (EAC) intraperitoneally implanted in albino mice. Sixty albino mice were divided equally into 4 groups. Group I mice (G1 control) were treated with physiologic saline solution for 7 days. Group 2 mice (G2) were injected with the partially purified protein. Group 3 mice (G3) were intraperitoneally inoculated with EAC cells and treated with the partially purified protein. Group 4 mice (G4) were inoculated EAC cells and treated with physiologic saline solution. The results showed a disturbance in liver functions. This disturbance was observed as a reduction in the values of serum albumin, hemoglobin, total counts of erythrocytes and platelets, total lipids in liver tissues, erythrocytes SOD activity, serum glucose, reduced glutathione (GSH) and the trace elements (Fe, Mn, Zn, and Cu) contents in liver and spleen tissues as well as the elevation of serum transaminases activities, the levels of malondialdehyde in blood, DNA and RNA of liver tissues in the infected mice (G4). On the other hand, in G3, after treatment with the partial purified protein all these parameters restored their normal values and became near from the normal group (GI). Moreover, the protein showed no toxicity towards the mice as shown in G2. It could be concluded 322that a partially purified protein with Superoxide Dismutase (SOD)-like activity extracted from leaves of Raphnus sativus as a nature source has a promised future in controlling liver metastasis.

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Section: Discussionmentioning

confidence: 99%

“…Permanent modification of genetic material resulting from these "oxidative damage" incidents represents the first step involved in mutagenesis, carcinogenesis and ageing [5]. In addition, a redox imbalance subsequently induces liver tumor-promoting effects by enhancing cellular proliferation in rats [9].…”

Section: Introductionmentioning

confidence: 99%

Suppression Effect of Superoxide Dismutase (SOD)-Like Activity Protein Partially Purified from <i>Raphnus sativus</i> Leaves against Liver Metastasis in Mice Intraperitoneally Infected with Ehrlich Ascites Carcinoma Cell

Toson¹,

Almutairi²,

Elfalal³

et al. 2016

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“…The threshold tumor promotion dose of PB and I3C was set as the low dose and combination dose, and the two-fold higher dose was set as the high dose in the present study. The threshold tumor promotion doses of PB and I3C were determined as 60 ppm (Kitano et al, 1998) and 2,500 ppm (Shimamoto et al, 2011b), respectively. To enhance hepatocyte proliferation, all rats underwent a two-thirds partial hepatectomy (PH) 1 week after the start of the treatment of PB or I3C.…”

Section: Experimental Designmentioning

confidence: 99%

“…Indole-3-carbinol (I3C) is an alkaloid contained in cruciferous vegetables, such as broccoli, Brussels sprouts, cabbage, and cauliflower (Higdon et al, 2007), and also has been shown to increase CYP1A mRNA expression in the liver of rats (Nho and Jeffery, 2001;Coe et al, 2006). Our group previously reported that I3C promoted hepatocellular tumors in parallel with the CYP1A induction potential to cause subsequent oxidative stress responses in rats (Shimamoto et al, 2011a(Shimamoto et al, , 2011b.…”

Section: Introductionmentioning

confidence: 99%

Modifying effects of liver tumor promotion in rats subjected to co-administration of indole-3-carbinol and phenobarbital

et al. 2014

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-Indole-3-carbinol (I3C) and phenobarbital (PB) are cytochrome P450 (CYP) 1A and CYP2B inducers, respectively, and have liver tumor-promoting effects in rats. In this study, we investigated the modifying effects on tumor promotion by I3C and PB co-administration. Six-week-old male F344 rats received a single intraperitoneal injection of N-diethylnitrosamine for initiation treatment. Two weeks after the initiation, rats were given no tumor-promoting agents (DEN alone), I3C (2,500 or 5,000 ppm in diet), PB (60 or 120 ppm in drinking water), or 2,500 ppm I3C + 60 ppm PB for 6 weeks. One week after the I3C/PB treatments, all animals underwent a two-thirds partial hepatectomy. The number and area of liver cell foci positive for glutathione S-transferase placental form (GST-P + foci) were not significantly fluctuated in the PB+I3C group in the isoadditive statistical model. On the contrary, the mRNA levels of Cyp2b1/2 and Nqo1 were suppressed and enhanced, respectively, in the PB+I3C group in the isoadditive model, but there was no enhancement in the microsomal reactive oxygen species (ROS) production, thiobarbituric acid-reactive substance levels, and Ki-67 + cell ratio in this group. The results suggest that the co-administration of I3C and PB causes no modifying effects in liver tumor promotion in rats.

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“…We have previously demonstrated that some CYP1A inducers such as BNF, indole-3-carbinol and oxfendazole, have liver tumor promoting effects in rats and induce oxidative stress including microsomal ROS generation and thiobarbituric acid-reactive substances (TBARS) production in the liver (Dewa et al, 2008(Dewa et al, , 2009Shimamoto et al, 2011a). We have also shown that a proton pump inhibitor, omeprazole (OPZ), which induces Cyp1a, also Enhanced liver tumor promotion but not liver initiation activity in rats subjected to combined administration of omeprazole and β-naphthoflavone has a liver tumor promoting effect in rats, but oxidative stress is not involved in the mechanism (Hayashi et al, 2012a).…”

Section: Introductionmentioning

confidence: 99%

Enhanced liver tumor promotion but not liver initiation activity in rats subjected to combined administration of omeprazole and β-naphthoflavone

et al. 2012

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-Omeprazole (OPZ) and β-naphthoflavone (BNF) are cytochrome P450 (CYP)1A inducers and have liver tumor promoting effects. In this study, we investigated the co-promoting and co-initiating effects of OPZ and BNF in rats. In Experiment 1, male rats were subjected to partial hepatectomy (PH), and given oral doses of 138 or 276 mg/kg OPZ, 0.125% or 0.25% BNF or 138 mg/kg OPZ+0.125% BNF (n = 9~12) for 6 weeks after N-diethylnitrosamine (DEN) initiation. In Experiment 2, male rats were treated with oral doses of 138 or 276 mg/kg OPZ, 0.03% or 0.06% BNF or 138 mg/kg OPZ+0.03% BNF (n = 11~12) for 9 days starting 1 week before initiating treatment. As an initiating treatment, 2-Amino-3,4-dimethylimidazo[4,5-f]quinolone (MeIQx) was orally administered 12 hr after PH. The rats were fed a basal diet for 15 days, followed by a diet containing 0.015% 2-acetylaminofluorene for the next 10 days with a single oral dose of carbon tetrachloride. In Experiment 1, the number and area of glutathione S-transferase placental form-positive foci in the OPZ+BNF group were significantly higher than the average values of the High OPZ or the High BNF group. The expression of cyclooxygenase-2 (Cox-2) and COX-2 protein in the liver significantly increased in the OPZ+BNF group. In Experiment 2, liver initiation activity was not enhanced by the co-administration of OPZ+BNF. The results of our studies suggest that the co-administration of OPZ and BNF results in synergistic effects in the liver tumor promotion probably owing to increased COX-2 expression, but no modifying effect in the liver initiation activity of MeIQx in rats.

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Indole-3-carbinol enhances oxidative stress responses resulting in the induction of preneoplastic liver cell lesions in partially hepatectomized rats initiated with diethylnitrosamine

Cited by 27 publications

References 52 publications

Suppression Effect of Superoxide Dismutase (SOD)-Like Activity Protein Partially Purified from <i>Raphnus sativus</i> Leaves against Liver Metastasis in Mice Intraperitoneally Infected with Ehrlich Ascites Carcinoma Cell

Suppression Effect of Superoxide Dismutase (SOD)-Like Activity Protein Partially Purified from <i>Raphnus sativus</i> Leaves against Liver Metastasis in Mice Intraperitoneally Infected with Ehrlich Ascites Carcinoma Cell

Modifying effects of liver tumor promotion in rats subjected to co-administration of indole-3-carbinol and phenobarbital

Enhanced liver tumor promotion but not liver initiation activity in rats subjected to combined administration of omeprazole and β-naphthoflavone

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Indole-3-carbinol enhances oxidative stress responses resulting in the induction of preneoplastic liver cell lesions in partially hepatectomized rats initiated with diethylnitrosamine

Cited by 27 publications

References 52 publications

Suppression Effect of Superoxide Dismutase (SOD)-Like Activity Protein Partially Purified from &lt;i&gt;Raphnus sativus&lt;/i&gt; Leaves against Liver Metastasis in Mice Intraperitoneally Infected with Ehrlich Ascites Carcinoma Cell

Suppression Effect of Superoxide Dismutase (SOD)-Like Activity Protein Partially Purified from &lt;i&gt;Raphnus sativus&lt;/i&gt; Leaves against Liver Metastasis in Mice Intraperitoneally Infected with Ehrlich Ascites Carcinoma Cell

Modifying effects of liver tumor promotion in rats subjected to co-administration of indole-3-carbinol and phenobarbital

Enhanced liver tumor promotion but not liver initiation activity in rats subjected to combined administration of omeprazole and β-naphthoflavone

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Suppression Effect of Superoxide Dismutase (SOD)-Like Activity Protein Partially Purified from <i>Raphnus sativus</i> Leaves against Liver Metastasis in Mice Intraperitoneally Infected with Ehrlich Ascites Carcinoma Cell

Suppression Effect of Superoxide Dismutase (SOD)-Like Activity Protein Partially Purified from <i>Raphnus sativus</i> Leaves against Liver Metastasis in Mice Intraperitoneally Infected with Ehrlich Ascites Carcinoma Cell