Diphenyl diselenide modulates antioxidant status, inflammatory and redox-sensitive genes in diesel exhaust particle-induced neurotoxicity.

This study seeks to determine the influence of diphenyl diselenide (DPDSe) on redox status, inflammatory and redox-sensitive genes in diesel exhaust particle (DEP)-induced neurotoxicity in male albino rats. Male Wistar albino rats were administered nasally with DEP (30 and 60 µg/kg) and treated with intraperitoneal administration of 10 mg/kg DPDSe. Non-enzymatic (lipid peroxidation and conjugated diene concentrations) and enzymatic (catalase, superoxide dismutase, glutathione peroxidase) antioxidant indices and activity of acetylcholinesterase enzyme were evaluated in brain tissues of the rats. Furthermore, the expression of genes linked to oxidative stress (HO-1, Nrf2), pro-inflammatory (NF-KB, IL-8, TNF-α) anti-inflammatory (IL-10) and brain-specific (GFAP, ENO-2) genes were also determined. The results indicated that DPDSe caused a notable reduction in the high levels of thiobarbituric acid reactive substances and conjugated diene observed in the brain of DEP-administered rats. DPDSe also reversed the observed reduction in catalase, superoxide dismutase and glutathione peroxidase enzyme activities in the brain of DEP-administered rats. Lastly, the downregulation of genes associated with redox homeostasis, anti-inflammatory and brain-specific genes and upregulation of pro-inflammatory genes observed in the DEP-treated groups were ameliorated by DPDSe. The immediate restoration of altered biochemical conditions and molecular expression in the brain of DEP-treated rats by DPDSe further validates its use as a promising therapeutic candidate for restoring neurotoxicity linked with DEP-induced oxidative stress.

Saponin from the fruit of Solanum anguivi protects against oxidative damage mediated by Fe2+ and sodium nitroprusside in rat brain synaptosome P2 fraction.

Solanum anguivi fruit saponin has antidiabetic property via interference with cellular energy metabolism and inhibition of reactive oxygen species (ROS) generation. In the current study, brain specific in vitro anti-oxidant role of S. anguivi saponin was investigated in the P2 synaptosomal fraction of rat brain. Using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction assay, S. anguivi saponin concentration- dependently (10-200 µg/ml) reversed Fe2+ and sodium nitroprusside- induced decrease in mitochondrial activity via inhibition of ROS production, ROS-induced oxidation of protein and non-protein thiol-containing molecules and lipid peroxidation as measured by thiobarbituric acid reactive substances levels. Conclusively, S. anguivi fruit saponin represents a class of natural compounds with the ability to reverse synaptosomal disruption, loss of mitochondrial integrity and function often associated with the progression of Huntington's disease, Alzheimer disease, Parkinson disease and amyotrophic lateral sclerosis diseases.

Influence of gallic acid on oxidative stress-linked streptozotocin-induced pancreatic dysfunction in diabetic rats.

BACKGROUND: Recent advances in diabetic research involve the evaluation of agents that can regenerate or reverse pancreatic dysfunction. Although gallic acid (GA) has been reported as an antidiabetic agent, its ability to directly reverse altered biochemical parameters in diabetic pancreas has not been demonstrated. METHODS: Male albino rats with diabetes induced by the administration of streptozotocin (STZ) (50 mg/kg, intraperitoneally) were treated with oral administration of GA. Antioxidants (enzymatic and non-enzymatic), purinergic enzymes, δ-aminolevulinic acid dehydratase and lactate dehydrogenase were evaluated in the pancreas of both diabetic and nondiabetic animals. RESULTS: The pharmacological effect of GA was accompanied by a restoration of the observed decreased levels of vitamin C and reduced glutathione in the pancreas of STZ-treated rats. GA also caused a marked reduction in the high levels of thiobarbituric acid reactive substances observed in the STZ-induced diabetic group. Furthermore, GA also improves the free radical scavenging property, Fe2+ chelating ability and Fe3+ reducing property of the pancreas of diabetic animals. Finally, the inhibition of pancreatic catalase, glutathione S-transferase, δ-aminolevulinic acid dehydratase and lactate dehydrogenase and increased activity of purinergic enzymes accompanied by hyperglycemia were prevented by GA in the pancreas. CONCLUSIONS: The direct influence and consequent restoration of altered biochemical conditions in the pancreatic tissue of diabetic animal models by GA makes it a promising antidiabetic candidate especially in pancreatic cell regeneration.

African eggplant (Solanum anguivi Lam.) fruit with bioactive polyphenolic compounds exerts in vitro antioxidant properties and inhibits Ca(2+)-induced mitochondrial swelling.

OBJECTIVE: To evaluate the antioxidant and radical scavenging activities of Solanum anguivi fruit (SAG) and its possible effect on mitochondrial permeability transition pore as well as mitochondrial membrane potential (ΔΨm) isolated from rat liver. METHODS: Antioxidant activity of SAG was assayed by using 2,2-diphenyl-1-picrylhydrazyl (DPPH), reducing power, iron chelation and ability to inhibit lipid peroxidation in both liver and brain homogenate of rats. Also, the effect of SAG on mitochondrial membrane potential and mitochondrial swelling were determined. Identification and quantification of bioactive polyphenolics was done by HPLC-DAD. RESULTS: SAG exhibited potent and concentration dependent free radical-scavenging activity (IC50/DPPH=275.03±7.8 µg/mL). Reductive and iron chelation abilities also increase with increase in SAG concentration. SAG also inhibited peroxidation of cerebral and hepatic lipids subjected to iron oxidative assault. SAG protected against Ca(2+) (110 µmol/L)-induced mitochondrial swelling and maintained the ΔΨm. HPLC analysis revealed the presence of gallic acid [(17.54±0.04) mg/g], chlorogenic acid (21.90±0.02 mg/g), caffeic acid (16.64±0.01 mg/g), rutin [(14.71±0.03) mg/g] and quercetin [(7.39±0.05) mg/g]. CONCLUSIONS: These effects could be attributed to the bioactive polyphenolic compounds present in the extract. Our results suggest that SAG extract is a potential source of natural antioxidants that may be used not only in pharmaceutical and food industry but also in the treatment of diseases associated with oxidative stress.

Catuaba (Trichilia catigua) prevents against oxidative damage induced by in vitro ischemia-reperfusion in rat hippocampal slices.

Oxidative stress is implicated in brain damage associated with ischemia-reperfusion. Natural antioxidants found in some plants used in folk medicine have been indicated as potential neuroprotective agents. Here we investigated whether Trichilia catigua, a traditional Brazilian herbal medicine alleged to exhibit a variety of neuropharmacological properties (antidepressant, anti-neurasthenic, anti-inflammatory etc.), could have neuroprotective properties in rat hippocampal slices subjected to 2 h oxygen and glucose deprivation (OGD) followed by 1 h reperfusion. Ischemia-reperfusion (I/R) significantly decreased mitochondrial viability, increased dichlorofluorescein oxidation above control both in the incubation medium and slices homogenates, increased lactate dehydrogenase into the incubation medium and decreased non-protein thiols. T. catigua (40-100 µg/mL) protected slices from the deleterious effects of OGD when present before OGD and during the reperfusion periods. Oxidative stress in the medium was also determined under different conditions and the results demonstrated that T. catigua could not protect slices from I/R when it was added to the medium after ischemic insult. Although the translation to a real in vivo situation of I/R is difficult to be done, the results indicated that T. catigua should be used as preventive and not as a curative agent against brain damage.

Mercury toxicity on sodium pump and organoseleniums intervention: a paradox.

Mercury is an environmental poison, and the damage to living system is generally severe. The severity of mercury poisoning is consequent from the fact that it targets the thiol-containing enzymes, irreversibly oxidizing their critical thiol groups, consequently leading to an inactivation of the enzyme. The Na⁺/K⁺-ATPase is a sulfhydryl protein that is sensitive to Hg²âº assault. On the other hand, organoseleniums are a class of pharmacologically promising compounds with potent antioxidant effects. While Hg²âº oxidizes sulfhydryl groups of Na⁺/K⁺-ATPase under in vitro and in vivo conditions, the organoselenium compounds inhibit Na⁺/K⁺-ATPase in vitro but enhance its activities under in vivo conditions with concomitant increase in the level of endogenous thiols. Paradoxically, it appears that these two thiol oxidants can be used to counteract one another under in vivo conditions, and this hypothesis serves as the basis for this paper.

In vitro antioxidant activity of stem bark of Trichilia catigua Adr. Juss.

Antioxidant activity of the ethanolic extract and fractions from the stem bark of T. catigua was investigated. IC50 (for DPPH scavenging) by T. catigua varied from 9.17 ± 0.63 to 76.42 ± 5.87 mg mL⁻¹ and total phenolic content varied from 345.63 ± 41.08 to 601.27 ± 42.59 mg GAE g⁻¹ of dry extract. Fe²âº-induced lipid peroxidation was significantly reduced by the ethanolic extract and fractions. Mitochondrial Ca²âº-induced dichlorofluorescein oxidation was significantly reduced by the ethanolic extract in a concentration-dependent manner. Ethanolic extract reduced mitochondrial Δψm only at high concentrations (40-100 mg mL⁻¹), which indicates that its toxicity does not overlap with its antioxidant effects. Results suggest involvement of antioxidant activities of T. catigua in its pharmacological properties.

Reduction of diphenyl diselenide and analogs by mammalian thioredoxin reductase is independent of their gluthathione peroxidase-like activity: a possible novel pathway for their antioxidant activity.

Since the successful use of the organoselenium drug ebselen in clinical trials for the treatment of neuropathological conditions associated with oxidative stress, there have been concerted efforts geared towards understanding the precise mechanism of action of ebselen and other organoselenium compounds, especially the diorganyl diselenides such as diphenyl diselenide, and its analogs. Although the mechanism of action of ebselen and other organoselenium compounds has been shown to be related to their ability to generally mimic native glutathione peroxidase (GPx), only ebselen however has been shown to serve as a substrate for the mammalian thioredoxin reductase (TrxR), demonstrating another component of its pharmacological mechanisms. In fact, there is a dearth of information on the ability of other organoselenium compounds, especially diphenyl diselenide and its analogs, to serve as substrates for the mammalian enzyme thioredoxin reductase. Interestingly, diphenyl diselenide shares several antioxidant and neuroprotective properties with ebselen. Hence in the present study, we tested the hypothesis that diphenyl diselenide and some of its analogs (4,4'-bistrifluoromethyldiphenyl diselenide, 4,4'-bismethoxy-diphenyl diselenide, 4.4'-biscarboxydiphenyl diselenide, 4,4'-bischlorodiphenyl diselenide, 2,4,6,2',4',6'-hexamethyldiphenyl diselenide) could also be substrates for rat hepatic TrxR. Here we show for the first time that diselenides are good substrates for mammalian TrxR, but not necessarily good mimetics of GPx, and vice versa. For instance, bis-methoxydiphenyl diselenide had no GPx activity, whereas it was a good substrate for reduction by TrxR. Our experimental observations indicate a possible dissociation between the two pathways for peroxide degradation (either via substrate for TrxR or as a mimic of GPx). Consequently, the antioxidant activity of diphenyl diselenide and analogs can be attributed to their capacity to be substrates for mammalian TrxR and we therefore conclude that subtle changes in the aryl moiety of diselenides can be used as tool for dissociation of GPx or TrxR pathways as mechanism triggering their antioxidant activities.

Sun-drying diminishes the antioxidative potentials of leaves of Eugenia uniflora against formation of thiobarbituric acid reactive substances induced in homogenates of rat brain and liver.

Extracts from leaves of Pitanga cherry (Eugenia uniflora) are considered to be effective against many diseases, and are therefore used in popular traditional medicines. In the present study, the antioxidative effect of sun-dried (PCS) and air-dried (PCA) ethanolic extracts of Pitanga cherry leaves were investigated. The antioxidant effects were tested by measuring the ability of both PCS and PCA to inhibit the formation of thiobarbituric acid reactive species (TBARS) induced by prooxidant agents such as iron (II) and sodium nitroprusside (SNP) in rat brain and liver tissues. The results showed that while PCA significantly (P<0.0001) inhibited the formation of TBARS in both liver and brain tissues homogenates, PCS did not. Further investigation reveals that the phenolic content of the PCS was significantly (P<0.0001) lower compared to PCA. Since phenolics in plants largely contributed to the antioxidative potency of plants, we conclude that air-drying should be employed in the preparation of extracts of Pitanga cherry leaves before it is administered empirically as a traditional medicament, and hence this study serves a public awareness to traditional medical practitioners.