Regulation of Nrf2 and Nrf2-related proteins by ganoderma lucidum in hepatocellular carcinoma.

BACKGROUND: HCC is among the most common cancer. Ganoderma lucidum (G.lucidum) has been essential in preventing and treating cancer. The Nrf2 signaling cascade is a cell protective mechanism against further damage, such as cancer development. This signaling pathway upregulates the cytoprotective genes and is vital in eliminating xenobiotics and reactive oxygen. This study aimed to show the potential cytotoxic activity of G. lucidum aqueous extract in HCC. METHODS AND RESULTS: MTT assay was used to detect cell viability. Nrf2-related proteins were measured by western blotting, and the flow cytometry method assayed cell population in different cycle phases. Cell viability was 49% and 47% following G. lucidum extract at 100 µg/ml at 24 and 48 h treatments, respectively. G. lucidum extract (aqueous, 100 or 50 µg/ml) treatments for 24, 48, or 72 h were able to significantly change the cytoplasmic/nuclear amount of Nrf2 and HO-1, NQO1 protein levels. Moreover, at both concentrations, arrest of the G0/G1 cell cycle was stimulated in HCC. CONCLUSIONS: The activation of the Nrf2 signaling pathways seems to be among the mechanisms underlining the protective and therapeutic action of G. lucidum against HCC.

The protective effect of resveratrol against dentin bonding agents-induced cytotoxicity.

This study was designed to evaluate the cytotoxicity of four dentin bonding agents and the effects of an antioxidant addition. Group A: G-aenial Bond, Group B: Optibond All in One, Group C: Gluma Self Etch and Group D: Clearfil S(3) Bond were added to the medium using extract method. The cells were cultured with or without resveratrol (RES) addition. MTT, reactive oxygen species (ROS), DCF, Comet and 8-OHdG measurements were performed. The agents had a dose-dependent (1:1>1:10>1:20) cytotoxic effect. Considering 1:10 concentration; Group D at 1 h (p<0.01) and Group B and D at 24 h had the weakest cytotoxic effect (p<0.05). After RES addition, the highest cell viability was determined in Groups B+RES and D+RES at 1 h and in Groups A+RES and B+RES at 24 h (p<0.01). The dentin bonding agents induced ROS production and DNA damage regarding to their composition. However, RES addition decreased the indicated parameters.

Effects of resveratrol on hydrogen peroxide-induced oxidative stress in embryonic neural stem cells.

Resveratrol, a natural phenolic compound, has been shown to prevent cardiovascular diseases and cancer and exhibit neuroprotective effects. In this study, we examined the neuroprotective and antioxidant effects of resveratrol against hydrogen peroxide in embryonic neural stem cells. Hydrogen peroxide treatment alone increased catalase and glutathione peroxidase activities but did not change superoxide dismutase levels compared with hydrogen peroxide + resveratrol treatment. Nitric oxide synthase activity and concomitant nitric oxide levels increased in response to hydrogen peroxide treatment. Conversely, resveratrol treatment decreased nitric oxide synthase activity and nitric oxide levels. Resveratrol also attenuated hydrogen peroxide-induced nuclear or mitochondrial DNA damage. We propose that resveratrol may be a promising agent for protecting embryonic neural stem cells because of its potential to decrease oxidative stress by inducing higher activity of antioxidant enzymes, decreasing nitric oxide production and nitric oxide synthase activity, and alleviating both nuclear and mitochondrial DNA damage.

The effect of hyperbaric oxygen on neuroregeneration following acute thoracic spinal cord injury.

AIMS: Although hyperbaric oxygen (HBO) treatment following spinal cord injury (SCI) have been studied in terms of neurological function and tissue histology, there is a limited number studies on spinal cord tissue enzyme levels. MAIN METHODS: The effect of HBO treatment in SCI was investigated by measuring superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), nitric oxide synthase (NOS) and nitric oxide (NO) activity in the injured tissue. SCI was induced by applying an aneurysm clip extradurally at the level of T9-T11 vertebrae. Preoperative HBO (preopHBO) treatment was applied for 5days and postoperative HBO (postopHBO) for 7days. KEY FINDINGS: In the preopHBO group, a significant decrease was observed in NOS and NO compared to the SCI group. There was a decrease in SOD, NOS and NO in the postopHBO group when compared to the SCI group. In the pre-postHBO group SOD, GPx, NOS and NO decreased significantly. There was a decrease in SOD in postopHBO compared to preopHBO. In the prepostopHBO, SOD decreased significantly compared to that in the preopHBO group. The prepostopHBO presented a significant decrease in GPx compared to postopHBO (p<0.05 for all parameters). No significant difference was observed for catalase for all groups. Significant improvement was found in BBB scores for both postopHBO and prepostHBO groups when compared to the SCI group (p<0.05). SIGNIFICANCE: HBO treatment was found to be beneficial following SCI in terms of biochemical parameters and functional recovery in the postoperative period.

Potential neuroprotective effect of gamma-glutamylcysteine ethyl ester on rat brain against kainic acid-induced excitotoxicity.

The aim of this study was to investigate the effect of gamma-Glutamylcysteine Ethyl Ester (GCEE) on the levels of GSH, caspase-3 activity, DNA damage and the expressions of Bcl-2, Bax and p53 mRNAs in rat hippocampus after status epilepticus (SE) induced by systemic kainic acid (KA). The male rats were divided into four groups as controls, KA (10 mg/kg), GCEE (10 mg/kg) and KA+GCEE. Glutathione (GSH) levels and caspase-3 activity were determined spectrophotometrically and colourimetrically, respectively. DNA damage and Bcl-2, Bax and p53 mRNA expressions were quantified by comet assay and reverse transcription followed by RT-PCR, respectively. KA treatment significantly depleted GSH levels, induced DNA damage, caspase-3 activity and the expressions of p53 and Bax mRNA. GCEE treatment protected GSH levels, decreased DNA damage and the levels of p53 and Bax/Bcl-2 mRNA against KA injection. These results indicate that GCEE treatment at the dose of 10 mg/kg is capable to protect the depleted levels of GSH and shows an anti-apoptotic activity due to the decreased levels of apoptotic biomarkers in the rat hippocampus after SE induced by KA.

Total phenolic contents, free radical scavenging activities and inhibitory effects on the activation of NF-kappa B of eight Centaurea L. species.

Extracts obtained from aerial parts of eight Centaurea L. (Asteraceae) species (C. calolepis, C. cariensis subsp. maculiceps, C. cariensis subsp. microlepis, C. hierapolitana, C. cadmea, C. ensiformis, C. depressa and C. urvillei subsp. urvillei), were tested for their free radical scavenging activity (FRSA) in the DPPH screening assay, for their in vitro antiinflammatory activity in the reporter gene assay for inhibition of transcription factor NF-kappaB and for their total phenolic content. Methanol extracts (0.25 mg/4 mL) of C. urvillei, C. cadmea and C. ensiformis showed strong antioxidant activity with 90.41 +/- 2.98%, 86.66 +/- 2.67% and 86.19 +/- 2.94% FRSA, respectively. Antioxidant capacity results were consistent with the total phenolic content. Chloroform extracts of C. hierapolitana, C. calolepis and C. cadmea showed strong in vitro antiinflammatory activity with IC(50) values of 2.5, 4.4 and 6.2 microg/mL, respectively.

The potential antioxidant effect of raloxifene treatment: a study on heart, liver and brain cortex of ovariectomized female rats.

The antioxidant activity of some compounds buffer the free radicals generated either endogenously or exogenously, thus decreasing the potential damage mediated by oxidation. Recent studies documented that raloxifene has antioxidant properties in vitro. However, there are limited animal studies available to show raloxifene's antioxidant properties. We aimed to investigate the effects of raloxifene on antioxidant enzymes such as SOD, CAT and GPX, TrxR and the levels of GSH and MDA in heart, liver and brain cortex of ovariectomized female rats. Female Sprague Dawley rats weighing 300-350 g (n=24) were divided into three groups: (I) Eight non-ovariectomized rats were used as naive controls without any treatment (non-ovariectomized group, n=8). Five weeks after ovariectomy, (II) Ovariectomized placebo group (n=8) was given physiological saline, and (III) Raloxifene group (n=8) was given raloxifene 1 mg/kg sc. daily for 12 days. Ovariectomy induced significant increases on SOD, GPX, CAT activity and MDA levels in brain, heart and liver tissues compared to non-ovariectomized rats ( p<0.05). Raloxifene treatment led to decreased levels of SOD activity in heart, GPX activity in brain and CAT activity in liver tissue when compared to ovariectomized group ( p<0.05) but there was no change in activity of TrxR in all groups. The levels of MDA in brain, heart and liver tissues increased in ovariectomized group when compared to non-ovariectomized rats ( p<0.05). Raloxifene had a significant attenuating effect on the levels of MDA in brain and heart tissues. Our results also indicate that the levels of GSH in brain, heart and liver tissue decreased when compared to non-ovariectomized rats. Raloxifene treatment was observed to significantly increase the levels of GSH in brain and heart tissues ( p<0.05). However, there were insignificant differences for the GSH levels in liver tissues of ovariectomized placebo or raloxifene groups. In conclusion, our results demonstrate that raloxifene may be more effective against oxidative stress in heart and brain than in liver tissue.

The protective effects of Achillea L. species native in Turkey against H(2)O(2)-induced oxidative damage in human erythrocytes and leucocytes.

The aim of the present study was to investigate the protective effects of infusions prepared from 15 Achillea (Asteraceae) species against H(2)O(2)-induced oxidative damage in human erythrocytes and leucocytes used in traditional Turkish medicine. CAT, SOD and GPx activities, effects of LPO and GSH levels of the infusions on erythrocytes and leucocytes were assessed. The results indicated that all infusions of Achillea species were effective on antioxidant enzyme systems of erythrocytes and leucocytes when compared with H(2)O(2) group. Achillea falcata was the most effective one on CAT, GPx and SOD enzyme systems of erythrocytes. Among plant infusions, Achillea crithmifolia and Achillea nobilis subsp. neilrechii showed the highest activities on CAT, while Achillea millefolium subsp. pannonica on SOD, Achillea teretifolia on GPx and Achillea nobilis subsp. sipylea on LPO enzyme systems of leucocytes. The present results demonstrate that infusions of Achillea species are a potential source of natural antioxidants for treatment and prevention of diseases in which LPO takes place.

The in vitro effects of Hypericum species on human leukocyte myeloperoxidase activity.

Myeloperoxidase (MPO) is a major component of the antimicrobial system of polymorphonuclear neutrophils. The heme enzyme MPO catalyzes the conversion of hydrogen peroxide and chloride to hypochlorous acid. Hypochlorous acid is the major strong oxidant produced by neutrophils and may contribute to inflammatory tissue damage. It was reported that certain antiinflammatory drugs are capable of inhibiting MPO activity and this inhibition may account for their antiinflammatory effect. Hypericum L. is a genus of about 400 species, widespread throughout the world. Some species of genus exhibit a significant antiinflammatory activity beside their several pharmacological properties such as antidepressant, diuretic, antihelmintic, and antibacterial. In this study, we investigated the in vitro effects of three Hypericum species, which exhibit antiinflammatory activity, on human polymorphonuclear leukocyte MPO activity. We found that each extract of Hypericum species reduced the peroxidative and chlorinating activity of human leukocyte MPO in concentration-dependent manner. The antiinflammatory activity of these species may be related with inhibition of MPO activity.

Essential oil composition and antioxidant activity of endemic Ziziphora taurica subsp. cleonioides.

The essential oil of Turkish endemic Ziziphora taurica subsp. cleonioides aerial parts was found to contain (+)-pulegone (81.86%), limonene (4.48%) and piperitenone (2.30%) activity. The essential oil showed relevant antioxidant activity.