Exposure to Ebselen Changes Glutamate Uptake and Release by Rat Brain Synaptosomes

We investigated effects of Ebselen, diphenyl diselenide (PhSe)₂ and diphenyl ditelluride (PhTe)₂ on [³H]glutamate uptake and release by brain synaptosomes. Ebselen after acute exposure inhibited K⁺-stimulated [³H]glutamate release by brain synaptosomes. (PhSe)₂ and (PhTe)₂ did not change [³H]glutamate release by brain synaptosomes. Ebselen, (PhSe)₂ and (PhTe)₂ had no significantly effects on [³H]glutamate uptake after acute exposure. In vitro, Ebselen (100 M) inhibited [³H]glutamate release and uptake. (PhSe)₂ had no significant effect, while (PhTe)₂ (100 M) inhibited [³H]glutamate uptake by brain synaptosomes. In vitro, (PhSe)₂, (PhTe)₂ and Ebselen caused a significant inhibition of [³H]glutamate uptake by brain synaptic vesicles in vitro. The results demonstrated that organochalcogenides have a rather complex effect on glutamate homeostasis depending on the compound and the schedule of exposition. We propose that the neuroprotective action of Ebselen can be related, in addition to its glutathione peroxidase-like and antilipoperoxidative activity, to a direct interaction with the glutamatergic system by reducing K^ï-evoked glutamate release.     

Rosmarinus officinalis essential oil modulates renal toxicity and oxidative stress induced by potassium dichromate in rats

BACKGROUNDChromium hexavalent (CrVI) is known as a toxic contaminant that induced oxidative stress and nephrotoxicity in humans and animals. Rosmarinus officinalis is a perennial herb rich in biologically active constituents that have powerful antioxidant properties. So, the current work evaluated the effectiveness of Rosmarinus officinalis essential oil (REO) against alterations induced by potassium dichromate in the kidney of male rats.METHODSGC-MS analysis, in vitro total phenol contents, and DPPH scavenging activity of REO were estimated. Thirty-five Wistar male rats were categorized into 5 groups. The first group was the control, the second one was orally administered rosemary essential oil (REO; 0.5 mL/kg BW), the third group was injected intraperitoneally with hexavalent chromium (CrVI; 2 mg/kg BW) for 14 days, the fourth group used as the protective group (REO was administrated 30 min before i.p. injection of CrVI) and the fifth group applied as the therapeutic group (rats injected with CrVI 30 min followed by oral administration of REO), respectively.RESULTSTwenty-nine components were detected with high total phenolic contents and high DPPH scavenging activity. Results revealed that CrVI- intoxicated rats showed a valuable increase in oxidative stress profile (TBARS and H₂O₂) and a notable decline in glutathione (GSH), total protein content, and enzymatic antioxidants (SOD, CAT, GPx, and GST). Furthermore, serum kidney functions biomarkers (urea, creatinine, and uric acid) were increased significantly. Also, the administration of CrVI showed histological and immunohistochemical (PCNA-ir) changes in rat kidney tissue. Otherwise, administration of REO pre or post-treatment with CrVI significantly restored most of the biochemical parameters in addition to improvement in kidney tissue architecture. Moreover, individual intake with REO exhibited an amendment in oxidative stress markers.CONCLUSIONConclusively, REO had a potential antioxidant capacity in ameliorating K₂Cr₂O₇-induced nephrotoxicity, especially in the protection group.     

Protective Effect of Diphenyl Diselenide on Ischemia and Reperfusion-Induced Cerebral Injury: Involvement of Oxidative Stress and Pro-Inflammatory Cytokines

Cerebrovascular diseases, including ischemic stroke, are associated with high mortality worldwide. Oxidative stress and inflammation are important pathophysiological mechanisms involved in post-ischemic cerebral injury. The present study was designed to investigate the potential protective effect of diphenyl diselenide (PhSe)₂, an organoselenium compound with antioxidant and anti-inflammatory properties, against ischemia/reperfusion (I/R) insult in rat brain. The experimental model adopted was that of surgically-induced brain ischemia, performed by means of bilateral common carotid artery occlusion in rats. The effect of a single oral dose of (PhSe)₂ (50 mg/kg), administered 30 min before the onset of ischemia, was investigated by assessing cerebral oxidative stress-related biochemical parameters and pro-inflammatory cytokines in plasma of rats. The results demonstrated an increase in the levels of malondialdehyde (MDA), reactive oxygen species (ROS) and nitrate/nitrite as well as the alteration in the non-enzymatic and enzymatic (catalase and superoxide dismutase) antioxidant defense system induced by I/R insult in rat brain. I/R insult increased the levels of IL-1β, IL-6, TNF-α and INF-γ in plasma of rats. The administration of (PhSe)₂ restored cerebral levels of MDA, ROS, nitrate/nitrite and antioxidant defenses of rats exposed to I/R insult. (PhSe)₂ markedly reduced pro-inflammatory cytokines in plasma of I/R rats. I/R insult increased the plasma levels of tissue damage markers, such as creatine kinase and α-1-acid glycoprotein. Pretreatment with (PhSe)₂ was effective in reducing the levels of these proteins. In addition, (PhSe)₂ attenuated cerebral histological alterations induced by I/R. This study showed for the first time the in vivo protective effect of (PhSe)₂ against oxidative stress and pro-inflammatory cytokines-induced by I/R insult in rats.     

Lignin-derived lignophenols attenuate oxidative and inflammatory damage to the kidney in streptozotocin-induced diabetic rats

Abstract

This study investigated the effects of lignin-derived lignophenols (LPs) on the oxidative stress and infiltration of macrophages in the kidney of streptozotocin (STZ)-induced diabetic rats. The diabetic rats were divided into four groups with 0%, 0.11%, 0.33% and 1.0% LP diets. The vehicle-injected controls were given a commercial diet. At 5 weeks, superoxide (O₂^?) production, macrophage kinetics, the degree of fibrosis in glomeruli and mRNA expression for monocyte chemoattractant protein-1 (MCP-1) were examined. The NADPH-stimulated O₂^? levels in the kidney of the diabetic rats treated with 1.0% LP were significantly lower than those in untreated diabetic rats. The number of macrophages, levels of MCP-1 mRNA expression and degree of glomerular fibrosis increased in untreated LP and these levels were significantly lower in 1.0%LP-treated rats. The results suggested that LPs suppress the excess oxidative stress, the infiltration and activation of macrophages and the glomerular expansion in STZ-induced diabetic kidneys.     

Ameliorative effect of carnosine and N-acetylcysteine against sodium nitrite induced nephrotoxicity in rats

The widespread use of sodium nitrite (NaNO₂) for various industrial purposes has increased human exposure to alarmingly high levels of nitrate/nitrite. Because NaNO ₂ is a strong oxidizing agent, induction of oxidative stress is one of the mechanisms by which it can exert toxicity in humans and animals. We have investigated the possible protection offered by carnosine (CAR) and N-acetylcysteine (NAC) against NaNO ₂-induced nephrotoxicity in rats. Animals orally received CAR at 100 mg/kg body weight/d for seven days or NAC at 100 mg/kg body weight/d for five days followed by a single oral dose of NaNO ₂ at 60 mg/kg body weight. The rats were killed after 24 hours, and the kidneys were removed and processed for various analyses. NaNO ₂ induced oxidative stress in kidneys, as shown by the decreased activities of antioxidant defense, brush border membrane, and metabolic enzymes. DNA-protein crosslinking and DNA fragmentation were also observed. CAR/NAC pretreatment significantly protected the kidney against these biochemical alterations. Histological studies supported these findings, showing kidney damage in NaNO ₂-treated animals and reduced tissue impairment in the combination groups. The protection offered by CAR and NAC against NaNO ₂-induced damage, and their nontoxic nature, makes them potential therapeutic agents against nitrite-induced nephrotoxicity.     

Effectiveness of (PhSe)2 in protect against the HgCl2 toxicity

This work investigated the preventive effect of diphenyl diselenide [(PhSe)₂] on renal and hepatic toxicity biomarkers and oxidative parameters in adult mice exposed to mercury chloride (HgCl₂). Selenium (Se) and mercury (Hg) determination was also carried out. Mice received a daily oral dose of (PhSe)₂ (5.0 mg/kg/day) or canola oil for five consecutive days. During the following five days, the animals were treated with a daily subcutaneous dose of HgCl₂ (5.0 mg/kg/day) or saline (0.9%). Twenty-four hours after the last HgCl₂ administration, the animals were sacrificed and biological material was obtained. Concerning toxicity biomarkers, Hg exposure inhibited blood δ-aminolevulinic acid dehydratase (δ-ALA-D), serum alanine aminotransferase (ALT) activity and also increased serum creatinine levels. (PhSe)₂ partially prevented blood δ-ALA-D inhibition and totally prevented the serum creatinine increase. Regarding the oxidative parameters, Hg decreased kidney TBARS levels and increased kidney non-protein thiol levels, while (PhSe)₂ pre-treatment partially protected the kidney thiol levels increase. Animals exposed to HgCl₂ presented Hg content accumulation in blood, kidney and liver. The (PhSe)₂ pre-treatment increased Hg accumulation in kidney and decreased in blood. These results show that (PhSe)₂ can be efficient in protecting against these toxic effects presented by this Hg exposure model.     

Fish oil rich in eicosapentaenoic acid protects against oxidative stress-related renal dysfunction induced by TCDD in Wistar rats

Humans are systemically exposed to persistent organic pollutants, of which 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has become a major environmental concern. Exposure to TCDD results in a wide variety of adverse health effects which is mediated by oxidative stress through CYP1A1 activation and arachidonic acid metabolites. Eicosapentaenoic acid (EPA) exhibits antioxidant property and competes with arachidonic acid in membrane phospholipids and produces anti-inflammatory EPA derivatives. Since both EPA and its derivatives have been reported to enhance the antioxidant mechanism, the present study aimed at studying whether EPA could offer protection against TCDD-induced oxidative stress and nephrotoxicity in Wistar rats. Estimation of kidney markers (serum urea and creatinine) and histopathological studies revealed that EPA treatment significantly reduced TCDD-induced renal damage. TCDD-induced oxidative damage was reflected in a significant increase in CYP1A1 activity and lipid peroxide levels with a concomitant decline in non-enzymic antioxidant (GSH) and various enzymic antioxidants such catalase (CAT), superoxide dismutase (SOD), glutathione-S-transferase (GST), and glutathione peroxidase (GPx). In addition, TCDD-induced oxidative stress also resulted in decline in Na⁺-K⁺ and Mg²⁺ATPases activities with increase in Ca²⁺ ATPases activity. Oral treatment with EPA showed a significant cytoprotection against TCDD-induced renal oxidative stress by decreased CYP1A1 activity and enhanced antioxidant status. TCDD-induced alterations in ATPase enzyme activities were also prevented by EPA treatment. Our results show clear evidence that EPA ameliorates TCDD-induced oxidative stress and kidney damage; thus suggest the potential of EPA as an effective therapeutic agent against toxic effects mediated through redox imbalance.     

Antioxidant effect of diphenyl diselenide on oxidative stress caused by acute physical exercise in skeletal muscle and lungs of mice

This study was designed to examine if diphenyl diselenide (PhSe)₂, an organoselenium compound, attenuates oxidative stress caused by acute physical exercise in skeletal muscle and lungs of mice. Swiss mice were pre‐treated with (PhSe)₂ (5 mg kg^‐1 day^‐1) for 7 days. At the 7th day, the animals were submitted to acute physical exercise which consisted of continuous swimming for 20 min. The animals were euthanized 1 and 24 h after the exercise test. The levels of thiobarbituric acid reactive species (TBARS), non‐protein thiols (NPSH) and ascorbic acid and the activity of catalase (CAT) were measured in the lungs and skeletal muscle of mice. Glycogen content was determined in the skeletal muscle of mice. Parameters in plasma (urea and creatinine) were determined. The results demonstrated an increase in TBARS levels induced by acute physical exercise in the skeletal muscle and lungs of mice. Animals submitted to exercise showed an increase in non‐enzymatic antioxidant defenses (NPSH and ascorbic acid) in the skeletal muscle. In lungs of mice, activity of CAT was increased. (PhSe)₂ protected against the increase in TBARS levels and ameliorated antioxidant defenses in the skeletal muscle and lungs of mice submitted to physical exercise. These results indicate that acute physical exercise caused a tissue‐specific oxidative stress in the skeletal muscle and lungs of mice. (PhSe)₂ protected against oxidative damage induced by acute physical exercise in mice. Copyright © 2009 John Wiley & Sons, Ltd.     

Secoisolariciresinol diglucoside protects against cadmium-induced oxidative stress-mediated renal toxicity in rats

BackgroundCadmium is a well known environmental pollutant and strong toxic heavy metal, that causes oxidative damage to various organs of the body, including the kidney. Cadmium (II) chloride (CdCl₂) is a water-soluble crystalline form, which exhibits a higher affinity with chlorides at the target site. The current study examined the protective effects of Secoisolariciresinol diglucoside (SDG), a principal lignan extracted from flaxseeds against CdCl₂-induced renal toxicity in rats.MethodsTwenty four healthy male Wistar rats with four groups of six animals each were used in the study. Group-1- Control was administered with saline. Group-2 –was treated with SDG; Group-3 with CdCl₂ alone, and Group-4 were treated with CdCl₂ plus SDG. The effect of Cd on kidney was assessed in terms of various parameters like lipid peroxidation, production of Nitric oxide (NO) and Myeloperoxidase (MPO), and kidney function markers like uric acid, urea, and creatinine. The levels of antioxidant molecules like glutathione content and the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase were also measured, apart from histopathological studies.ResultsThe animals that received CdCl₂, exhibited changes in the concentration of Cd in the kidney. The levels of kidney function markers like uric acid, urea, and creatinine were found to be abnormal in serum, and also there was a drastic decrease in the levels of glutathione content and the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase. The treatment of SDG significantly decreased (p < 0.05) the levels of NO and MPO in the animals treated with CdCl₂ plus SDG when compared to the animal group treated with CdCl₂ alone. The treatment of SDG before CdCl2 injection exhibited significant changes in the activity of the antioxidant enzymes, which was evidenced by the restoration in their activities, when compared to CdCl2 alone treated group (p < 0.05), as observed in the results of histopathology.ConclusionsThe findings of the present investigation suggested that SDG exhibited anti-oxidant, anti-apoptotic and renoprotective properties. Thus, SDG may act as a supramolecular binding component and naturally occurring metal chelating agent for metal cations like Cd²⁺. Therefore, flaxseed lignan-SDG can be used as a therapeutic agent against nephrotoxicity caused by cadmium. However, detailed future studies are needed to know the underlying mechanism of action of SDG against the Cd and other heavy metals induced nephrotoxicity.     

Diphenyl diselenide (PhSe)2 inhibits biofilm formation by Candida albicans,increasing both ROS production and membrane permeability

ProjectThe opportunistic fungal Candida albicans can produce superficial and systemic infections in immunocompromised patients. An essential stage to both colonization and virulence by C. albicans is the transition from budding yeast form to filamentous form, producing biofilms.ProcedureIn this work, we studied the effect of the organochalcogenide compound (PhSe)₂ on both cell growth and biofilm formation by C. albicans.Results(PhSe)₂ inhibited both growth and biofilm formation by C. albicans. The inhibitory effects of (PhSe)₂ depended on the cell density and (PhSe)₂ concentration. We have also observed that (PhSe)₂ stimulated ROS production (67%) and increased cell membrane permeability (2.94-fold) in C. albicans. In addition, (PhSe)₂ caused a marked decrease in proteinase activity (6.8-fold) in relation to non-treated group.Conclusions(PhSe)₂ decreased both cell growth and biofilm development, decreasing the release of extracellular proteinases, which is an important facet of C. albicans pathogenicity. The toxicity of (PhSe)₂ towards C. albicans can be associated with an increase in ROS production, which can increase cell permeability. The permanent damage to the cell membranes can culminate in cell death.     

Diphenyl diselenide and diphenyl ditelluride: neurotoxic effect in brain of young rats, in vitro

This study examined whether maturity of rat brain may be relevant for the sensitivity to diphenyl diselenide (PhSe)₂ and diphenyl ditelluride (PhTe)₂ on [³H]glutamate uptake and release, in vitro. Brain synaptosomes were isolated from young (14- and 30-day-old) and adult rats and incubated at different concentrations of (PhSe)₂ or (PhTe)₂. The results demonstrated that the highest concentration (100 μM) of (PhSe)₂ and (PhTe)₂ inhibited the [³H]glutamate uptake by synaptosomes of brain at all ages. In the adult brain, (PhSe)₂ did not inhibit the [³H]glutamate uptake at the lowest concentration (10 μM). The highest concentration of (PhTe)₂ inhibited the [³H]glutamate uptake more in the 14-day-old than in the 30-day-old rats or adult rats. In the 30-day-old animals, the highest concentration of (PhSe)₂, and the lowest concentration of (PhTe)₂, increased the basal [³H]glutamate release. At the highest concentration, (PhTe)₂ increased the basal and K⁺-stimulated glutamate release on all ages evaluated. The results suggest that (PhSe)₂ and (PhTe)₂ caused alterations on the homeostasis of the glutamatergic system at the pre-synaptic level. These alterations were age-, concentration-, and compound-dependent. The maturity of rat brain is relevant for the glutamatergic system sensitivity to (PhSe)₂ and (PhTe)₂ .     

Diphenyl Diselenide Prevents Cortico-cerebral Mitochondrial Dysfunction and Oxidative Stress Induced by Hypercholesterolemia in LDL Receptor Knockout Mice

Recent studies have indicated a causal link between high dietary cholesterol intake and brain oxidative stress. In particular, we have previously shown a positive correlation between elevated plasma cholesterol levels, cortico-cerebral oxidative stress and mitochondrial dysfunction in low density lipoprotein receptor knockout (LDLr^?/?) mice, a mouse model of familial hypercholesterolemia. Here we show that the organoselenium compound diphenyl diselenide (PhSe)₂ (1 mg/kg; o.g., once a day for 30 days) significantly blunted the cortico-cerebral oxidative stress and mitochondrial dysfunction induced by a hypercholesterolemic diet in LDLr^?/? mice. (PhSe)₂ effectively prevented the inhibition of complex I and II activities, significantly increased the reduced glutathione (GSH) content and reduced lipoperoxidation in the cerebral cortex of hypercholesterolemic LDLr^?/? mice. Overall, (PhSe)₂ may be a promising molecule to protect against hypercholesterolemia-induced effects on the central nervous system, in addition to its already demonstrated antiatherogenic effects.     

DMPS and N-acetylcysteine induced renal toxicity in mice exposed to mercury

Acute effects of mercuric chloride (HgCl₂) were evaluated on mice. Mice received a single dose of HgCl₂ (4.6 mg/kg, subcutaneously) for three consecutive days. Thirty minutes after the last injection with HgCl₂, mice received one single injection of 2,3-dimercapto-1-propanesulfonic acid (DMPS) or N-acetylcysteine (NAC) or diphenyl diselenide (PhSe)₂. DMPS, NAC and (PhSe)₂ were utilized as therapy against mercury exposure. At 24 h after the last HgCl₂ injection, blood, liver and kidney samples were collected. δ-Aminolevulinate dehydratase (δ-ALA-D) and Na⁺, K_-⁺ ATPase activities, thiobarbituric acid-reactive substances (TBARS), non-protein thiols (NPSH) and ascorbic acid concentrations were evaluated. Plasma aspartate (AST) and alanine (ALT) aminotransferase activities, as well as urea and creatinine levels were determined. The group of mice exposed to Hg + (PhSe)₂ presented 100% of lethality. Exposure with HgCl₂ caused a decrease on the body weight gain and treatments did not modify this parameter. δ-ALA-D, AST and ALT activities, TBARS, ascorbic acid levels and NPSH (hepatic and erythrocytic) levels were not changed after HgCl₂ exposure. HgCl₂ caused an increase in renal NPSH content and therapies did not modify these levels. Mice treated with (PhSe)₂, Hg + NAC and Hg + DMPS presented a reduction in plasma NPSH levels. Creatinine and urea levels were increased in mice exposed to Hg + NAC, while Hg + DMPS group presented an increase only in urea level. Na⁺, K_-⁺ ATPase activity was inhibited in mice exposed to Hg + DMPS and Hg + NAC. In conclusion, therapies with (PhSe)₂, DMPS and NAC following mercury exposure must be better studied because the formation of more toxic complexes with mercury, which can mainly damage renal tissue.     

New Therapeutic Approach: Diphenyl Diselenide Reduces Mitochondrial Dysfunction in Acetaminophen-Induced Acute Liver Failure

The acute liver failure (ALF) induced by acetaminophen (APAP) is closely related to oxidative damage and depletion of hepatic glutathione, consequently changes in cell energy metabolism and mitochondrial dysfunction have been observed after APAP overdose. Diphenyl diselenide [(PhSe)₂], a simple organoselenium compound with antioxidant properties, previously demonstrated to confer hepatoprotection. However, little is known about the protective mechanism on mitochondria. The main objective of this study was to investigate the effects (PhSe)₂ to reduce mitochondrial dysfunction and, secondly, compare in the liver homogenate the hepatoprotective effects of the (PhSe)₂ to the N-acetylcysteine (NAC) during APAP-induced ALF to validate our model. Mice were injected intraperitoneal with APAP (600 mg/kg), (PhSe)₂ (15.6 mg/kg), NAC (1200 mg/kg), APAP+(PhSe)₂ or APAP+NAC, where the (PhSe)₂ or NAC treatment were given 1 h following APAP. The liver was collected 4 h after overdose. The plasma alanine and aspartate aminotransferase activities increased after APAP administration. APAP caused a remarkable increase of oxidative stress markers (lipid peroxidation, reactive species and protein carbonylation) and decrease of the antioxidant defense in the liver homogenate and mitochondria. APAP caused a marked loss in the mitochondrial membrane potential, the mitochondrial ATPase activity, and the rate of mitochondrial oxygen consumption and increased the mitochondrial swelling. All these effects were significantly prevented by (PhSe)₂. The effectiveness of (PhSe)₂ was similar at a lower dose than NAC. In summary, (PhSe)₂ provided a significant improvement to the mitochondrial redox homeostasis and the mitochondrial bioenergetics dysfunction caused by membrane permeability transition in the hepatotoxicity APAP-induced.     

The potential effects of pomegranate (Punica granatum) juice on carbon tetrachloride-induced nephrotoxicity in rats

The purpose of this study was to evaluate the effect of pomegranate (Punica granatum) in inhibiting and reversing the nephrotoxicity of carbon tetrachloride, a potent oxidative stress inducer which induces cellular kidney damage. Rats were intraperitoneally injected with carbon tetrachloride (2 mL/kg body weight) which produced severe renal tissue damage, as demonstrated by decreased uric acid and dramatic elevation of urea and creatinine. In addition, carbon tetrachloride injection caused oxidative stress in rats, as evidenced by increased lipid peroxidation and nitrite/nitrate (NO _x ) concentrations in the renal tissue, along with a remarkable reduction in superoxide dismutase, catalase, glutathione transferase, glutathione reductase, glutathione peroxidase activities and glutathione content. We suggested that pomegranate juice was able to elevate the antioxidant defense system, clean up free radicals, lessen oxidative damages and protect the kidney against carbon tetrachloride-induced toxicity, thus having a potential protective effect.     

Nigella sativa oil attenuates chronic nephrotoxicity induced by oral sodium nitrite: Effects on tissue fibrosis and apoptosis

Objectives: Sodium nitrite, a food preservative, has been reported to increase oxidative stress indicators such as lipid peroxidation, which can affect different organs including the kidney. Here, we investigated the toxic effects of oral sodium nitrite on kidney function in rats and evaluated potential protective effects of Nigella sativa oil (NSO).

Methods: Seventy adult male Sprague–Dawley rats received 80?mg/kg sodium nitrite orally in the presence or absence of NSO (2.5, 5, and 10?ml/kg) for 12 weeks. Morphological changes were assessed by hematoxylin and eosin, Mallory trichome, and periodic acid–Schiff staining. Renal tissues were used for measurements of oxidative stress markers, C-reactive protein, cytochrome C oxidase, transforming growth factor (TGF)-beta1, monocyte chemotactic protein (MCP)-1, pJNK/JNK, and caspase-3.

Results: NSO significantly reduced sodium nitrite-induced elevation in serum urea and creatinine, as well as increasing normal appearance of renal tissue. NSO also prevented reductions in glycogen levels caused by sodium nitrite alone. Moreover, NSO treatment resulted in dose-dependent significant reductions in fibrosis markers after sodium nitrite-induced 3- and 2.7-fold increase in MCP-1 and TGF-beta1, respectively. Finally, NSO partially reduced the elevated caspase-3 and pJNK/JNK.

Discussion: NSO ameliorates sodium nitrite-induced nephrotoxicity through blocking oxidative stress, attenuation of fibrosis/inflammation, restoration of glycogen level, amelioration of cytochrome C oxidase, and inhibition of apoptosis.     

Taurine ameliorates potassium bromate-induced kidney damage in rats

Potassium bromate (KBrO₃) is widely used as a food additive and is a major water disinfection by-product. Several studies have shown that it causes nephrotoxicity in humans and experimental animals. We have investigated the potential role of the sulfonic amino acid taurine in protecting the kidney from KBrO₃-induced damage in rats. Animals were randomly divided into four groups: control, KBrO₃ alone, taurine alone and taurine + KBrO₃. Administration of single oral dose of KBrO₃ alone caused nephrotoxicity as evident by elevated serum creatinine and urea levels. Renal lipid peroxidation and protein carbonyls were increased while total sulfhydryl groups and reduced glutathione levels were decreased suggesting the induction of oxidative stress. The enzymes of renal brush border membrane were inhibited and those of carbohydrate metabolism were altered. There was an increase in DNA damage and DNA–protein cross-linking. Treatment with taurine, prior to administration of KBrO₃, resulted in significant attenuation in all these parameters but the administration of taurine alone had no effect. Histological studies supported these biochemical results showing extensive renal damage in KBrO₃-treated animals and greatly reduced tissue injury in the taurine + KBrO₃ group. These results show that taurine is an effective chemoprotectant against bromate-induced renal damage and this amino acid could prove to be useful in attenuating the toxicity of this compound.     

Pycnogenol prevents potassium dichromate (K2Cr2O7)-induced oxidative damage and nephrotoxicity in rats

Environmental and occupational exposure to chromium compounds, especially hexavalent chromium [Cr(VI)], is widely recognized as a potential nephrotoxic in humans and animals. Its toxicity is associated with overproduction of free radicals, which induces oxidative damage. Recent evidence indicates that Pycnogenol^® (PYC), French maritime pine bark extract, exhibits antioxidant potential and protects against various oxidative stressors. The aim of the present study was to examine the modulating impacts of PYC on potassium dichromate (K₂Cr₂O₇)-induced oxidative damage and nephrotoxicity in rats. Male Wistar rats were divided into four groups. The first group was control, the second group was control plus pre-treated with PYC (10 mg/kg, body weight; in saline; intraperitoneally; once daily for 3 weeks) as drug control and the third group was saline pre-treated plus treated with a single injection of K₂Cr₂O₇ (15 mg/kg, body weight; in saline; intraperitoneally) as toxicant group. The fourth group was PYC pre-treated plus K₂Cr₂O₇ injected. Forty-eight hours after K₂Cr₂O₇-treatment, blood was drawn for estimation of renal injury markers in serum. Rats were then sacrificed, and their kidneys were dissected for biochemical and histopathological assays. K₂Cr₂O₇-treated rats showed significant increases in markers of renal injury in serum, including blood urea nitrogen (BUN), serum creatinine (Scr), and alkaline phosphatase (ALP), which were significantly (P < 0.05) decreased by PYC pre-treatment. Moreover, prophylactic pre-treatment of rats with PYC significantly (P < 0.05) ameliorated increased thiobarbituric reactive substances (TBARS), malonaldehyde (MDA) and protein carbonyl (PC), and decreased levels of glutathione (GSH) and catalase activity in the kidney homogenate of K₂Cr₂O₇-treated rats. These results were also supported and confirmed with histopathological findings. The study suggests that PYC is effective in preventing K₂Cr₂O₇-induced oxidative mediated nephrotoxicity, but more studies are needed to confirm the effects of PYC as a nephroprotective agent.     

Impact of SIN-1-derived peroxynitrite flux on endothelial cell redox homeostasis and bioenergetics: protective role of diphenyl diselenide via induction of peroxiredoxins

Abstract

Increased production of reactive nitrogen (RNS) and oxygen (ROS) species and its detrimental effect to mitochondria are associated with endothelial dysfunction. This study was designed to determine the effect of a peroxynitrite flux, promoted by 1,3-morpholinosydnonimine (SIN-1), in mitochondrial function and some redox homeostasis parameters in bovine aortic endothelial cells (BAEC). Moreover, the effect of diphenyl diselenide (PhSe)₂, a simple organic selenium compound, in preventing peroxynitrite-mediated cytotoxicity was also investigated. Our results showed that overnight exposure to SIN-1 (250 μM) caused a profound impairment of oxygen consumption, energy generation and reserve capacity in mitochondria of BAEC. Mitochondrial dysfunction resulted in an additional intracellular production of peroxynitrite, amplifying the phenomenon and leading to changes in redox homeostasis. Moreover, we observed an extensive decline in mitochondrial membrane potential (ΔΨ_m) induced by peroxynitrite and this event was associated with apoptotic-type cell death. Alternatively, the pretreatment of BAEC with (PhSe)₂, hindered peroxynitrite-mediated cell damage by preserving mitochondrial and endothelial function and consequently preventing apoptosis. The protective effect of (PhSe)₂ was related to its ability to improve the intracellular redox state by increasing the expression of different isoforms of peroxiredoxins (Prx–1–3), efficient enzymes in peroxynitrite detoxification.