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Whole-body irradiation has been associated with liver function alterations. Ionizing radiation exposure increases oxidative stress and antioxidants can activate transcription of antioxidant target genes. In the present study, modifications of the liver antioxidant system were evaluated at 7 and 30 days following sub-lethal whole-body X-irradiation in male Wistar rats, which were intragastrically supplemented with quercetin or control solvent for 4 days prior to and 6 days following irradiation. Animal groups were as follows: CS, control, solvent-supplemented; CQ, control, quercetin-supplemented; RS, irradiated, solvent-supplemented; and RQ, irradiated, quercetin-supplemented. After 7 days, liver tissue from RS animals demonstrated marked hydropic panlobular degeneration with Mallory bodies in ballooning hepatocytes. These changes were mostly reversed in RQ rats. Lipid peroxidation in addition to copper/zinc superoxide dismutase (Cu/Zn-SOD), nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and Kelch-like ECH-associated protein 1 (Keap1) protein expression levels were all increased by X-irradiation, but significantly decreased by quercetin supplementation. Catalase (CAT) and, Nad(p)h: quinone oxidoreductase 1 (NQO1) expression levels remained high in irradiated rats regardless of quercetin supplementation. After 30 days, the liver from RS animals had small portal infiltrates and diffuse cytoplasmic vacuolization, with reduced lipid peroxidation and reduced expression levels of CAT, NQO1, Nrf2 and Keap1, but consistently elevated Cu/Zn-SOD expression. RQ animals indicated reduced expression levels of Nrf2 and Keap1 30 days after irradiation. The present study demonstrated a quercetin-induced reduction of the oxidative stress-associated increase in Nrf2 expression that may be useful for preventing cancer cell survival in response to ionizing radiation exposure.

Aims: The aim of this study was to evaluate the potential protective effects of ad libitum black grape (Vitis labrusca) juice against liver oxidative damage in whole-body acute X-irradiated rats., Main Methods: Animals were fed ad libitum and drank voluntarily black grape juice or placebo (isocaloric glucose and fructose solution) for 6 days before and 15 days following a 6 Gy X-irradiation from a 200 kV machine., Key Findings: Irradiated animals receiving placebo showed a significant increase in the concentration of thiobarbituric acid-reactive substances (TBARS), a marker of lipid peroxidation, as well as a significant decrease in both Cu/Zn superoxide dismutase (Cu/ZnSOD) and glutathione peroxidase (GPx) activity and reduced glutathione concentration (GSH). Black grape juice supplementation resulted in a reversal of lipid peroxidation, Cu/ZnSOD activity, and GSH concentration, towards values not significantly differing from those in non-irradiated, placebo-supplemented rats. Poly(ADP-ribose) polymerase (PARP-1) and Cu/ZnSOD changes in protein expression were observed for irradiated rats. No change in p53 expression or DNA fragmentation was found., Significance: Ad libitum black grape juice intake is able to restore the liver primary antioxidant system against adverse effects due to whole-body acute X-irradiation in rats after 15 days post-irradiation. The results support using antioxidant supplements as a preventive tool against radiation-induced harm., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The objective of this study was to determine in a rat model of hepatocarcinoma (HCC) the effects of the antiangiogenic agent TNP-470 on antioxidant enzymes, including catalase (CAT), superoxide dismutases (Mn-SOD and Cu,Zn-SOD), and glutathione peroxidase (GPx). Tumor was induced in male Wistar rats by diethylnitrosamine and promoted by two-thirds hepatectomy plus acetaminofluorene administration. Experiments were carried out 28 weeks after initiating the treatment. TNP-470 was administered at 30 mg/kg, 2 times per week from weeks 20 to 28. Carcinomatous tissue was growing outside dysplastic nodules in rats with HCC. HCC caused oxidative stress demonstrated by increased lipid peroxidation and oxidized/reduced glutathione ratio that was accompanied by a reduced activity of antioxidant enzymes Cu,Zn-SOD, GPx, and CAT. In contrast, Mn-SOD activity and expression were higher in hepatocarcinoma than in control groups. These effects were absent in animals receiving TNP-470. No significant differences between untreated and TNP-470-treated rats were observed in the expression of the Cu,Zn-SOD, glutathione peroxidise, and CAT. We conclude that TNP-470 inhibits expression and activity of Mn-SOD induced by experimental hepatocarcinogenesis. Oxidative stress reduction by TNP-470 accounts for yet another anti-cancer effect of this molecule.

We examined the effect of daily melatonin supplementation on liver apoptosis induced by aging in rats. Young (3-month-old) and aged (24-month-old) Wistar rats were supplemented daily with melatonin in their drinking water (20 mg/L) for 4 weeks. Aged rats showed increases in the liver concentration of thiobarbituric acid-reactive substances and in the oxidized/reduced glutathione ratio. These increases were accompanied by apoptotic ultrastructural alterations and increases in cytochrome c mitochondrial release, Bax to Bcl-2 relative expression, and activity of caspase-3. No significant changes were observed in Fas-ligand (Fas-L) expression and caspase-8 activity. Melatonin administration was able to abrogate changes detected in aged rats. Data suggest that liver apoptotic cell death is induced by reactive oxygen species, via the intrinsic signalling pathway, and that the antiapoptotic action provided by melatonin is related to its antioxidant effect, with reduction of cytochrome c release by the modulation of Bcl-2 and Bax genes.

This study compared the effects of melatonin supplementation on markers of oxidative stress, and on the activity and expression of antioxidant enzymes in the liver of young (3-month-old) and aging (24-month-old) rats. Animals were supplemented with melatonin in the drinking water (20 mg/L) for 4 wk. Liver concentration of thiobarbituric-reactive substances (TBARS), as an index of lipid peroxidation, and the oxidized to reduced glutathione ratio significantly increased in aged rats (+58%), while values did not significantly differ from the young in aged animals receiving melatonin. Significant decreases in the liver activities of Cu,Zn-superoxide dismutase (SOD) (-25%), cytosolic (-21%) and mitochondrial (-40%) glutathione peroxidase (GPx), and catalase (CAT) (-34%) were found in aged rats. Melatonin abolished these changes and also prevented the reduction of Cu,Zn-SOD (-33%), cytosolic GPx (-30%), and mitochondrial GPx (-47%) liver protein content as measured by Western blot. Reductions in Cu,Zn-SOD mRNA (-39%), and GPx mRNA (-86%) levels induced by aging were also abolished by melatonin. In summary, our data indicate that melatonin treatment abrogates oxidative stress in the liver of aged rats, and that prevention of the decreased activity of CAT and the downregulation of Cu,Zn-SOD and GPx gene expression contribute to this effect.