Protective Effect Of Α-tocopherol Research Articles

Protective Effects of α-Tocopherol and N-Acetyl-Cysteine on Diazinon-Induced Oxidative Stress and Acetylcholinesterase Inhibition in Rats

ABSTRACTDiazinon, an organophosphate (OP) insecticide, is widely used in agriculture and domestically. Reactive oxygen species (ROS) caused by OPs are involved in the toxicity of various pesticides. The aim of the present study was to analyze the role of diazinon in inducing oxidative stress in adult male Wistar rats and to evaluate the possible protective effects of α-tocopherol (TPH) and the glutathione prodrug N-acetyl-cysteine (NAC) after 4 weeks of exposure to a sublethal dose of diazinon. TPH (10 mg/kg/day), NAC (160 mg/kg/day), diazinon (25 mg/kg/day), a combination of NAC (160 mg/kg/day) and diazinon (25 mg/kg/day), and a combination of TPH (10 mg/kg/day) and diazinon (25 mg/kg/day) were given to rats orally via gavage for 4 weeks. The thiobarbituric acid reactive substances (TBARS) marker of lipid peroxides levels, total thiol molecules, and total antioxidant capacity of plasma were all analyzed as biomarkers of oxidative stress. In addition, the acetylcholinesterase (AChE) activity was measured as a biomarker of toxicity. The results from this study well indicate diazinon-induced oxidative stress demonstrated by enhanced TBARS, decreased total thiol molecules, and total antioxidant capacity. In addition, AChE activity was inhibited as a marker of OP toxicity. Data show the protective roles of TPH and NAC in reducing the diazinon-induced oxidative stress. Interestingly, both TPH and NAC recovered diazinon-induced AChE inhibition. It is concluded that supplementation with TPH and NAC can reduce toxicity of OP in human exposure.

Antioxidants and coronary artery disease among individuals with type 1 diabetes: Findings from the Pittsburgh Epidemiology of Diabetes Complications Study

Objective Oxidative stress has been implicated in the development of diabetes and cardiovascular disease. We evaluated the effect of serum antioxidants and total antioxidant reserve (TAR) on coronary artery disease (CAD) incidence in type 1 diabetes. Methods Subjects were identified from the Pittsburgh Epidemiology of Diabetes Complications Study (EDC) cohort, a 10-year prospective study of childhood-onset type 1 diabetes. Mean age at baseline was 28 and diabetes duration 19 years. Coronary artery disease was defined as physician-diagnosed angina, confirmed MI, stenosis ≥50%, ischemic electrocardiogram (ECG), or revascularization. Controls were gender, age, and diabetes duration (±3 years) matched with cases. Samples and risk factors used in analyses were identified from the earliest exam prior to incidence in cases (54 cases, 67 controls). Results None of the antioxidant measures (α-tocopherol, γ-tocopherol, retinol, TAR) showed protection against incident CAD overall. However, a protective effect of α-tocopherol against CAD was observed among antioxidant supplement users (HR=0.22, 95% CI=0.10–0.49) and in renal disease (HR=0.46, 95% CI=0.23–0.91). Despite similar α-tocopherol concentration, there was no protective effect among nonusers of antioxidant supplements. Conclusions High α-tocopherol levels among patients with renal disease and in those using vitamin supplements were associated with lower CAD risk in type 1 diabetes. The specificity of these effects merits further investigation.

Role of α-tocopherol on antioxidant status in liver, lung and kidney of PCB exposed male albino rats

Polychlorinated biphenyls (PCB) are widespread, lipophilic environmental pollutants which have been identified as contaminants in almost every component of the global ecosystem including fish, wildlife, and human adipose tissue, breast milk, and serum. Several studies have shown that PCBs can cause oxidative damage to biomolecules, in the form of lipid peroxidation, modulation of antioxidant enzymes, and oxidative stress. In the present study, we have sought to investigate the effects of α-tocopherol (vitamin E) on antioxidant status of PCB-induced toxicity in male Wistar rats. The protective effect of α-tocopherol (50 mg/kg body weight/day) was tested in PCB-induced toxicity in rat liver, lung, and kidney. We report here that the oral supplementation of α-tocopherol was found to maintain the cellular redox status by maintaining the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase accompanied with glutathione and vitamin E levels and down regulation in the levels of lipid peroxides, hydroxyl radical and hydrogen peroxides generation in PCB treated rats. Therefore, our present study demonstrates the PCB-induced deficits in antioxidant enzyme activities and increase in reactive oxygen species and lipid peroxidation levels in liver, kidney, and lung which can be overcome through simultaneous supplementation with α-tocopherol.

Cytotoxic effects of various stressors on PC12 cells: Involvement of oxidative stress and effect of antioxidants

In order to specifically elucidate the involvement of oxidative stress, the effects of various types of stressors and antioxidants on PC12 cells were examined. In this study, the following four stressors were studied in detail: free radicals generated from 2,2′-azobis(2-amidinopropane) dihydrochloride (AAPH), 4-hydroxynonenal (HNE), 7-ketocholesterol (KC), and arsenic trioxide (As 2O 3). Undifferentiated PC12 cells were treated with 50% lethal concentration (LC 50) of these stressors, and subsequently the viability, apoptosis/necrosis ratio, reactive oxygen species (ROS) production, caspase-3 activity, and protection by antioxidants were measured to elucidate the underlying mechanisms that determine the action of these stressors on PC12 cells. The cytotoxicity did not correlate directly with the intracellular formation of ROS. For example, as compared to AAPH, As 2O 3 produced considerably smaller amounts of ROS at LC 50. As observed in the cells incubated with As 2O 3, KC and HNE exerted cell toxicity, but with a moderate production of ROS. With the exception of HNE, the apoptosis/necrosis ratio of all the stressors evaluated by annexin V and propidium iodide assays increased with an increase in the incubation time at the LC 50 values of these stressors. In accordance with apoptosis ratio, caspase activity was detected in the cells incubated with AAPH, As 2O 3, and KC, but not HNE at LC 50 for 24 h. The protective effect of α-tocopherol, 17β-estradiol, 2,3-dihydro-5-hydroxy-2,2-dipentyl-4,6-di- tert-butylbenzofuran (BO653), glutathione, and N-acetylcysteine (NAC) against cytotoxicity depended on the type of stressors. These antioxidants were found to be effective against the abovementioned stressors, except As 2O 3 against which only NAC was effective. These results suggest that the involvement of ROS and the protective effect of antioxidants depend on the type of stressors.

α-Tocopherol protects against α-naphthylisothiocyanate-induced hepatotoxicity in rats less effectively than melatonin

The protective effect of α-tocopherol (α-Toc), which exerts antioxidant and anti-inflammatory actions, against α-naphthylisothiocyanate (ANIT)-induced hepatotoxicity in rats was compared with that of melatonin because orally administered melatonin is known to protect against ANIT-induced hepatotoxicity in rats through its antioxidant and anti-inflammatory actions. Rats intoxicated once with ANIT (75 mg/kg, intraperitoneal (i.p.)) showed liver cell damage and biliary cell damage with cholestasis at 24 h, but not 12 h, after intoxication. ANIT-intoxicated rats received α-Toc (100 or 250 mg/kg) or melatonin (100 mg/kg) orally at 12 h after intoxication. The α-Toc administration protected against liver cell damage in ANIT-intoxicated rats, while the melatonin administration protected against both liver cell damage and biliary cell damage with cholestasis. ANIT-intoxicated rats had increased hepatic lipid peroxide concentration and myeloperoxidase activity at 12 and 24 h after intoxication. ANIT-intoxicated rats also had increased serum α-Toc and non-esterified fatty acid (NEFA) concentrations at 12 and 24 h after intoxication and increased serum triglyceride and total cholesterol concentrations at 24 h. The administration of α-Toc to ANIT-intoxicated rats increased the hepatic α-Toc concentration with further increase in the serum α-Toc concentration and attenuated the increased hepatic lipid peroxide concentration and myeloperoxidase activity and serum NEFA concentration at 24 h after intoxication. The melatonin administration did not affect the hepatic α-Toc concentration but attenuated the increased hepatic lipid peroxide concentration and myeloperoxidase activity and serum α-Toc, NEFA, triglyceride, and total cholesterol concentrations at 24 h after ANIT intoxication. These results indicate that orally administered α-Toc protects against ANIT-induced hepatotoxicity in rats possibly through its antioxidant and anti-inflammatory actions less effectively than orally administered melatonin.

Alpha-tocopherol protects against the renal damage caused by potassium dichromate

Exposure to hexavalent chromium (Cr 6+) causes mutagenic, carcinogenic, and toxic effects, some of which have been associated with its oxidative capacity. In the kidney, Cr 6+ has been claimed to provoke necrosis of the proximal tubular cells. Our aim was to assess the functional involvement of the different segments that form the nephron in a model of acute renal failure caused by potassium dichromate and the participation of oxidative damage in this process. We also studied the possible protective effect of α-tocopherol (α-TOC) against renal damage. Wistar female rats 200 g body weight (bw) received potassium dichromate (15 mg/kg, sc, single dose). Lipid peroxidation and renal function were evaluated on days 0, 1, 2, 3, 7, 10, and 14. A second group received α-TOC (125 mg/kg, by gavage) 5 days before and during dichromate exposure (same dose as for the first group), and was monitored at 0, 2, and 7 days of exposure. Creatinine clearance, glucose and sodium fractional excretions, p-aminohippurate uptake, free-water and osmolal clearances were also measured. Thiobarbituric acid-reactive substances were quantified in renal cortex. The results revealed altered proximal tubule function, decreased glomerular filtration, and distal segment dysfunction, accompanied by oxidative damage 48 h after exposure to dichromate. In the α-TOC-treated group proximal reabsorptive and secretory functions were preserved, suggesting that oxidative damage is a participating mechanism in dichromate toxicity on these functions. In contrast α-TOC did not prevent glomerular or distal dysfunction, indicating selectivity of the protection afforded by this compound on the toxicity of dichromate, at the several components of the nephron.

Protective effects of α-tocopherol and ischemic preconditioning on hepatic reperfusion injury

This study evaluated the effect of alpha-tocopherol (alpha-TC), ischemic preconditioning (IPC) or a combination on the extent of mitochondrial injury caused by hepatic ischemia/reperfusion (I/R). Rats were pretreated with alpha-TC (20 mg/kg per day, i.p.) for 3 days before sustained ischemia. A rat liver was preconditioned with 10 min of ischemia and 10 min of reperfusion, and was then subjected to 90 min of ischemia followed by 5 h or 24 h of reperfusion. I/R increased the aminotransferase activity and mitochondrial lipid peroxidation, whereas it decreased the mitochondrial glutamate dehydrogenase activity. alpha-TC and IPC individually attenuated these changes. alpha-TC combined with IPC (alpha-TC+IPC) did not further attenuate the changes. The mitochondrial glutathione content decreased after 5 h reperfusion. This decrease was attenuated by alpha-TC, IPC, and alpha-TC+IPC. The significant production of peroxides observed after 10 min reperfusion subsequent to sustained ischemia was attenuated by alpha-TC, IPC, and alpha-TC+IPC. The mitochondria isolated after I/R were rapidly swollen. However, this swelling rate was reduced by alpha-TC, IPC, and alpha-TC+IPC. These results suggest that either alpha-TC or IPC reduces the level of mitochondrial damage associated with oxidative stress caused by hepatic I/R, but alpha-TC combined with IPC offers no significant additional protection.

High nitrate intake impairs liver functions and morphology in rats; protective effects of α-tocopherol

The aim of this study was to determine the effect of high dose nitrate ingested in drinking water, on liver enzymes and histopathology, liver weight/body weight (lw/bw) ratio, serum and liver malondialdehyde (MDA) levels and osmotic fragility in Sprague–Dawley rats. These parameters were compared on 40 rats divided into four groups; control animals (group A) drank filtered tap water containing maximum 10 mg/L nitrate while treatment groups drank 200 mg/L (group B), 400 mg/L (group C) and α-tocopherol plus 400 mg/L (group D) nitrate containing water ad libitum for 60 days. As a result, lw/bw ratio increased significantly ( p < 0.05) among rats that consumed water with 400 mg/L nitrate. Osmotic fragility increased significantly in treatment groups ( p < 0.05 versus control). Liver but not serum MDA levels increased in group C ( p < 0.05 versus control). Group A showed normal hepatic lobular architecture and histology. After nitrate administration, there was hepatocellular degeneration with increased intercellular space of the liver cells in groups B and C. Liver MDA, osmotic fragility and liver histology have returned to nearly normal in group D. These findings show clearly that high nitrate ingestion can cause pathological changes in liver histology and functions. Moreover, α-tocopherol can prevent these effects, possibly through antioxidant properties.

Protective effects of α-tocopherol and tiopronin against cisplatin-induced ototoxicity

ObjectiveTo investigate the possible protective effects of α-tocopherol and tiopronin against cisplatin-induced cochlear damage. Cisplatin ototoxicity and nephrotoxicity seem to result from the inhibition of cochlear antioxidant defences, causing an increase in the amount of reactive oxygen species. Antioxidants, such as α-tocopherol and tiopronin, are able to suppress lipid peroxidation, thus attenuating tissue damage. Material and MethodsHartley albino guinea pigs were used. The animals were treated for 7 consecutive days with either (I) cisplatin alone, (II) cisplatin+α-tocopherol acetate, (III) cisplatin+tiopronin, (IV) cisplatin+α-tocopherol acetate+tiopronin, (V) α-tocopherol acetate alone or (VI) tiopronin alone. Changes in cochlear function were characterized by means of compound action potential threshold shifts. After the functional testing, tympanic bullae were removed and processed for morphological examination of the sensorineural epithelium. Renal function was evaluated by measuring serum blood urea nitrogen and creatinine levels. ResultsCisplatin induced progressive high-frequency hearing loss of 40–50 dB SPL. α-Tocopherol and tiopronin co-therapy significantly slowed the progression of hearing loss. Treatment with α-tocopherol acetate or tiopronin alone was less effective. Morphological observations showed an important loss of outer hair cells and degeneration of the organ of Corti in the basal and middle turns. Injection of both α-tocopherol and tiopronin reduced cochlear outer hair cell loss more than treatment with a single drug. Beneficial effects of α-tocopherol and tiopronin on cisplatin-induced nephrotoxicity were observed. Conclusion This study supports the hypothesis that α-tocopherol and tiopronin interfere with cisplatin-induced damage, and suggests that concurrent treatment with the two drugs can be useful in protecting against hearing loss.

Inhibitory effect of α-tocopherol on methylmercury-induced oxidative steress

The present study investigated the involvement of oxidative stress in the degeneration of the cerebellum during methylmercury (MeHg) intoxication and the protective effect of α-tocopherol (Vit E) against MeHg toxicity. After 5 mg/kg of MeHg was administered to Wistar rats for 12 consecutive days, the cerebellum were examined histopathologically. In addition, the same amount of MeHg was administered to 3 different groups of Wistar rats: rats with a Vit E-deficient diet, rats fed 150 mg/kg of Vit E for 20 consecutive days after initial MeHg administration, and rats with an ordinary diet. Positive immunoreactivity against anti-hydroxynonenal (HNE), a marker of lipid peroxidation, was observed in the cerebellum after MeHg administration. Levels of thiobarbituric acid reactive substance (TBARS), another marker of lipid peroxidation, and those of protein carbonyl, a biomarker for protein oxidation, increased after MeHg administration. In the rats with MeHg and a Vit E-deficient diet, mortality and prevalence of piloerection significantly increased, and in the rats with MeHg and Vit E, mortality, piloerection, retracted and crossed hind leg, and ataxic gait significantly decreased, compared with the rats with MeHg alone. The levels of NO(2) (-) and NO(3) (-) in the serum significantly increased in the rats with MeHg alone 14 days after the initial MeHg administration, but were significantly suppressed by Vit E administration. Oxidative stress, especially lipid peroxidation, may play an important role in the cerebellar degeneration process during MeHg intoxication and Vit E may play a protective role against MeHg toxicity as an effective antioxidant.

α-Tocopherol protective effects on gentamicin ototoxicity: an experimental study

Gentamicin, acting as an iron chelator, activates membrane lipid peroxidation (MPL) and induces free radical formation, as observed in vitro and in vivo. Antioxidants, such as α-tocopherol, are able to suppress MLP, thus attenuating tissue damage. The present study was designed to investigate the possible protective effects of α-tocopherol on gentamicin ototoxicity. The study was carried out on albino guinea pigs (250–350 g). The animals were divided into four groups: group A (n = 4), injected with corn oil daily at a dose of 100 mg/kg body weight intramuscularly (IM); group B (n = 10), treated with corn oil at a dose of 100 mg/kg body weight and gentamicin base at a dose of 100 mg/kg body weight (IM); group C (n = 10), treated with gentamicin alone at a dose of 100 mg/kg body weight (IM); and group D (n 10), treated with gentamicin at the same dose plus α-tocopherol acetate at dose of 100 mg/kg body weight (IM). Electrocochleographic recordings were made from an implanted round-window electrode. All animals were treated for 14 days. The compound action potentials (CAPs) were measured at 2–16 kHz at days 0, 10, 14 and 18 after treatment. Changes in cochlear function were characterized as CAP threshold shifts. Morphological changes were analysed by scanning electron microscopy. Gentamicin induced progressive high-frequency hearing loss of 50–60 dB SPL. α-tocopherol co-therapy slowed the progression of hearing loss. The significant loss of outer hair cells (OHCs) in the cochlear basal turn in gentamicin-treated animals was not observed in the cochleas of animals protected with α-tocopherol. This study supports the hypothesis that α-tocopherol interferes with gentamicin-induced free radical formation, and suggests that this drug may be useful in protecting OHC function from aminoglycoside ototoxicity, thus reducing hearing loss.

Induction of apoptosis and cell cycle arrest by polyvinylpyrrolidone K-30 and protective effect of α-tocopherol

Polyvinylpyrrolidone is a macromolecular polymer with widespread use in industry as well as in medicine for various purposes. Its effect on cells cultured in vitro, however, has not been fully investigated. To elucidate this issue, we studied the influence of PVP K-30 on cultured HeLa cells. PVP K-30 treatment produced a dose- and time-dependent toxicity to HeLa cells. Cells exposed to PVP K-30 exhibited several morphological features of apoptosis. Gel electrophoresis of DNA from PVP K-30-treated cells showed typical apoptotic ladder. And flow cytometric analysis demonstrated that PVP K-30 induced cell cycle arrest at G2/M phase and the subsequent appearance of sub-G1 population. In addition, it was shown that procaspase-3 was activated in response to PVP K-30 treatment. We also found that α-tocopherol efficiently protected HeLa cells from PVP K-30 cytotoxicity. This is the first demonstration that PVP K-30 could induce apoptosis in HeLa cells and cell cycle arrest at G2/M phase, and that PVP K-30 toxicity could be attenuated by α-tocopherol.

Protective Effects of α-Tocopherol Against Gentamicin-induced Oto-vestibulo Toxicity: An Experimental Study

Objective—Free radicals are involved in gentamicin ototoxicity and vestibular dysfunction and it has been demonstrated that free radical scavengers, such as α-tocopherol, are able to inactive free radicals, attenuating tissue damage. This study was designed to investigate the possible protective effects of α-tocopherol against gentamicin-induced oto-vestibulo toxicity.Material and Methods—Adult albino guinea pigs were divided into four groups and were treated for 2 weeks as follows: Group A, controls; Group B, gentamicin plus corn oil; Group C, gentamicin only; and Group D, gentamicin plus α-tocopherol. To evaluate vestibular function, the animals underwent sinusoidal oscillations in the dark about their vertical and longitudinal axes to evoke horizontal and vertical vestibulo-ocular reflexes (VORs), respectively. Electrocochleographic recordings were performed using an implanted round window electrode. The compound action potentials (CAPs) at 2, 4, 8 and 16 kHz were measured every 5 days. Morphological changes were analysed by means of scanning electron microscopy.Results—Gentamicin induced a consistent reduction in VOR responses and a progressive high-frequency hearing loss of 50–60 dB sound pressure level. α-Tocopherol co-therapy slowed the progression of hearing loss and significantly attenuated the final threshold shifts. The impairment of vestibular function was reduced, as evidenced by an increased VOR gain. The massive loss of outer hair cells in the cochlear basal turn and of cristae ampullaris stereocilia in gentamicin-treated animals was not observed in the cochlea of animals protected with α-tocopherol.Conclusion—This study supports the hypothesis that α-tocopherol interferes with gentamicin-induced free radical formation, and suggests that this drug may be useful in preventing aminoglycoside oto-vestibulo toxicity.

Cadmium-induced toxicity on testicular tissue and spermatogenesis in rats and the protective effects of α-tocopherol

Objective: Cadmium is known to exert toxic effects on multiple organs, including the testes. The objective of this study was to determine if α-tocopherol, an antioxidant, could protect testicular tissues and spermatogenesis from the toxic effects of cadmium.

656 Poster Protective effect of α-tocopherol on radiation induced rectal damage in wistar rat

656 Poster Protective effect of α-tocopherol on radiation induced rectal damage in wistar rat

Genotoxicity of Malaoxon: Induction of Oxidized and Methylated Bases and Protective Effect of α-Tocopherol

Abstract Malaoxon, the first and main metabolite of malathion, unlike its parent compound, can damage DNA in human lymphocytes, by mechanism(s) including oxidative action. Vitamin C may inhibit the DNA-damaging effect of malaoxon. To explore this effect further, we investigated the action of malaoxon on DNA in lymphocytes pretreated with a potent antioxidant, α-tocopherol (vitamin E), using the single-cell gel electrophoresis (comet assay). Addition of α-tocopherol to a final concentration of 20 and 80 μM reduced a dose-dependent DNA damaging effect of a 1-h incubation of human peripheral blood lymphocytes at 37°C with malaoxon at 25, 75, or 200 μM, measured as the increase in the comet tail moment of the lymphocytes. Lymphocytes treated with α-tocopherol displayed faster kinetics of removing damage to their DNA, and α-tocopherol abolished the cytotoxic effect of malaoxon at 200 μM. The protective action of α-tocopherol followed from its interaction with DNA or with malaoxon bound to DNA or lymphocytes rather than from chemical inactivation of malaoxon by it. Catalase, an enzyme inactivating hydrogen peroxide, decreased the extent of DNA damage induced by malaoxon. Lymphocytes exposed to malaoxon and treated with formamidopyrimidine-DNA glycosylase and 3-methyladenine-DNA glycosylase II, enzymes recognizing oxidized and methylated bases, displayed a greater extent of DNA damage than those not treated with these enzymes. The results suggest that hydrogen peroxide and reactive oxygen species may be involved in the formation of DNA lesions induced by malaoxon. Malaoxon can also methylate DNA bases, and α-tocopherol can be considered a protective agent against DNA damage in persons occupationally exposed to malathion/malaoxon.

Antioxidants prevent depletion of [Mg 2+] i induced by alcohol in cultured canine cerebral vascular smooth muscle cells: Possible relationship to alcohol-induced stroke

Low serum concentrations of Mg 2+ ions have been reported, recently, in patients with coronary disease, atherosclerosis, and stroke as well as in patients with cerebral hemorrhage. The aim of the present study was to determine whether potent antioxidants [α-tocopherol and pyrrolidine dithiocarbamate (PDTC)] can prevent or ameliorate intracellular Mg 2+ ([Mg 2+] i) depletion associated with cerebral vascular injury induced by alcohol. Exposure of cultured canine cerebral vascular smooth muscle cells to alcohol (10–100 mM) for 24 h induced marked depletion in [Mg 2+] i (i.e., ∼ 30–65%, depending upon alcohol concentration). Treatment of the cultured cells with either PDTC (0.1 μM) or α-tocopherol (15 μM) for 24 h, alone, failed to interfere with basal [Mg 2+] i levels. However, preincubation of the cells with either α-tocopherol or PDTC for 24 h completely inhibited the depletion of [Mg 2+] i induced by exposure to 10–100 mM ethanol. These results indicate that α-tocopherol and PDTC prevent decreases in [Mg 2+] i produced by ethanol. Moreover, these new results suggest that such protective effects of α-tocopherol and PDTC on cerebral vascular cells might be useful therapeutic tools in prevention and amelioration of cerebral vascular injury and stroke in alcoholics.

Protective effects of α-tocopherol and β-carotene on para-nonylphenol-induced inhibition of cell growth, cellular respiration and glucose-induced proton extrusion of bacteria

para-Nonylphenol (NP) showed a dose-dependent inhibition against the cell growth of Bacillus subtilis, Micrococcus luteus, Pseudomonas aeruginosa and Staphylococcus aureus at 5–100 μM. However, other typical plastic-derived endocrine disruptors such as bisphenol A and di-2-ethylhexyl phthalate (DEHP) did not significantly affect the cell growth of these bacteria at 5–100 μM. The NP-induced cell growth inhibition was restored when concomitantly supplemented with lipophilic antioxidants such as α-tocopherol and β-carotene, but not with hydrophilic antioxidants, ascorbic acid and (−)-epigallocatechin gallate (EGCG). NP also suppressed in a dose-dependent manner cellular oxygen consumption and glucose-induced proton extrusion of these bacteria at 10–100 μM. Both effects were prevented when added with α-tocopherol and β-carotene, but not with ascorbic acid and EGCG. The significance of these results is discussed from the viewpoint of environmental microbiology and a possible biochemical mechanism of the inhibitory effect of NP is suggested.

Antioxidants prevent elevation in [Ca 2+] i induced by low extracellular magnesium in cultured canine cerebral vascular smooth muscle cells: possible relationship to Mg 2+ deficiency-induced vasospasm and stroke

Low serum concentrations of Mg 2+ ions have been reported, recently, in patients with coronary disease, atherosclerosis and stroke as well as in patients with cerebral hemorrhage. The aim of the present study was to determine whether potent antioxidants [α-tocopherol and pyrrolidine dithiocarbamate (PDTC)] can prevent or ameliorate intracellular Ca 2+ ([Ca 2+] i) overload associated with cerebral vascular injury induced by low extracellular free Mg 2+ ([Mg 2+] o). Exposure of cultured canine cerebral vascular smooth muscle cells to low [Mg 2+] o (0.15–0.6 mM) vs. normal [Mg 2+] o (1.2 mM) for either 10 min or 2 h induced concentration-dependent rises in [Ca 2+] i. Treatment of the cultured cells with either PDTC (0.1 μM) or α-tocopherol (15 μM) for 24 h, alone, failed to interfere with basal [Ca 2+] i levels. However, preincubation of the cells with either α-tocopherol or PDTC for 24 h completely inhibited the elevation of [Ca 2+] i induced by exposure to low [Mg 2+] o, not only for 10 min, but also for 2 h. These results indicate that α-tocopherol and PDTC prevent rises in [Ca 2+] i produced by low [Mg 2+] o, which probably result from low [Mg 2+] o-induced lipid peroxidation of cerebral vascular smooth muscle cell membranes. Moreover, these new results suggest that such protective effects of α-tocopherol and PDTC on cerebral vascular cells might be useful therapeutic tools in cerebral vascular injury associated with low [Mg 2+] o and accumulation of [Ca 2+] i.

Enhancement of the anti-ischemic kidney resistance by adaptive hypoxic preconditioning and drug therapy

Hypoxic preconditioning and pretreatment with pentoxifylline, α-tocopherol, or their combination promotes stabilization of Po2 in rabbit kidney cortex in the early reperfusion period (in experiments with α-tocopherol at a significantly lower level), while after 30-min reperfusion, the protective effect of α-tocopherol (especially in combination with pentoxifylline) markedly surpasses that of pentoxifylline and hypoxic preconditioning. α-Tocopherol sharply inhibits LPO in the reperfusion period, while pentoxifylline exhibits only weak antioxidant activity and hypoxic preconditioning was ineffective.