Lipid peroxidation depends on the clock 3111T/C gene polymorphism in menopausal women with Insomnia

ABSTRACT

A comparative analysis of lipid peroxidation processes and antioxidant defense system in Caucasian menopausal women with/without insomnia depending on the genotype of Clock 3111T/C gene polymorphism was performed. Two hundred and fourteen Caucasian menopausal women divided into control (without insomnia) and main group (with insomnia) were examined. Lipid peroxidation (conjugated dienes, thiobarbituric acid reactants) and antioxidant defense system parameters (?-tocopherol, retinol, reduced and oxidized glutathione, glutathione S-transferase, glutathione peroxidase, glutathione reductase, superoxide dismutase) were determined by spectrofluorophotometer and immunoenzymometric methods. Patients with insomnia carriers of the TT-genotype had a significantly higher thiobarbituric acid reactants level and glutathione peroxidase activity as compared to group with insomnia carriers of the minor 3111C-allele (p < .05). A comparative analysis of the parameters in the women of the main and control groups showed higher conjugated dienes, thiobarbituric acid reactants levels and lower retinol, reduced glutathione levels, glutathione reductase activity in women with insomnia carriers of the TT-genotype (p < .05). The carriers of the minor allele with insomnia had a higher conjugated dienes levels and lower glutathione peroxidase activity as compared to control (p < .05). Thus, lipid peroxidation and antioxidant system parameters in Caucasian menopausal women with insomnia depend on the Clock 3111T/C gene polymorphism.     

Selenium modulates peroxidation in the absence of glutathione peroxidase in Musca domestica

Adult houseflies fed a low-selenium diet showed a 73% decrease in total Se compared to those given 1.0 ppm Se in their drinking water. This decrease was associated with a 84.4% increase in thiobarbituric acid reactants and a 16.3% increase in conjugated dienes. These increases were unrelated to activities of glutathione S-transferases, superoxide dismutases and catalase and to levels of reduced and oxidized glutathione, all of which were unaltered by Se deficiency. Since houseflies lack glutathione peroxidase, Se apparently modulates peroxidation in these animals independent of the antioxidant enzymes and glutathione.     

Effects of antioxidant vitamins A, C, E and trace elements Cu, Se on CuZn SOD, GSH-Px, CAT and LPO levels in chicken erythrocytes

The biologically damaging effects of reactive oxygen species are controlled in vivo by a wide spectrum of antioxidant defence mechanisms. Dietary constituents of antioxidant vitamins and trace elements may play an important role in protecting against oxidant damage. The effects of supplementation of vitamins A, C, E and trace elements Cu and Se on the activities of antioxidant enzymes and lipid peroxide levels in chicken erythrocytes were investigated depend on the time. CuZnSOD activity and plasma Cu levels in the Cu group were increased by 39 and 37 per cent respectively. CuZnSOD activity in vitamin C groups was also increased by 20 per cent. The GSH-Px activity in Se, Se+E and Se+Cu groups was raised by 35, 46 and 69 per cent respectively. Also, the GSH-Px activity in the vitamin C group was increased by 33 per cent. Catalase activity in all of these groups was not significantly different when compared with controls (p<0.01). The maximum decrease in LPO levels of 42 per cent was obtained for the Se+E group.     

Hepatoprotective and antioxidant effect of tender coconut water on carbon tetrachloride induced liver injury in rats

Hepatoprotective and antioxidant effects of tender coconut water (TCW) were investigated in carbon tetrachloride (CCl4)-intoxicated female rats. Liver damage was evidenced by the increased levels of serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT) and decreased levels of serum proteins and by histopathological studies in CCl4-intoxicated rats. Increased lipid peroxidation was evidenced by elevated levels of thiobarbituric acid reactive substance (TBARS) viz, malondialdehyde (MDA), hydroperoxides (HP) and conjugated dienes (CD), and also by significant decrease in antioxidant enzymes activities, such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (Gpx) and glutathione reductase (GR) and also reduced glutathione (GSH) content in liver. On the other hand, CCl4-intoxicated rats treated with TCW retained almost normal levels of these constituents. Decreased activities of antioxidant enzymes in CCl4-intoxicated rats and their reversal of antioxidant enzyme activities in TCW treated rats, shows the effectiveness of TCW in combating CCl4-induced oxidative stress. Hepatoprotective effect of TCW is also evidenced from the histopathological studies of liver, which did not show any fatty infiltration or necrosis, as observed in CCl4-intoxicated rats.     

Multivitamin and mineral supplementation in 1,2-dimethylhydrazine induced experimental colon carcinogenesis and evaluation of free radical status, antioxidant potential, and incidence of ACF

This study was performed to determine the chemopreventive and antioxidant status of multivitamin and mineral (0.01% in drinking water, ad libitum) supplements in 1,2-dimethylhydrazine (DMH)-induced experimental colon carcinogenesis. Experimental colon carcinogenesis was induced in male albino Wistar rats by injecting DMH (20 mg·(kg body mass)(-1)) once weekly for 15 consecutive weeks, and administering a multivitamin supplement in 3 regimes (initiation, post-initiation, and entire experimental period) for 32 weeks. We studied lipid peroxidation products (thiobarbituric acid reactive substances, lipid hydroperoxides, conjugated dienes) in the circulation and in the tissues, antioxidant status (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and non-enzymatic antioxidant-reduced glutathione) of the tissues, aberrant crypt foci (ACF), and histopathological alterations. DMH-induced rats had an increase in lipid peroxidation products and a lower antioxidant status compared with control animals. Multivitamin and mineral supplementation during the initiation, post-initiation, and the entire study period significantly decreased the levels of lipid peroxidation products in circulation and colonic tissues, significantly elevated the activities of the antioxidant enzymes and reduced glutathione to near normalcy in DMH-induced rats. The incidence of ACF was reduced by [corrected] 84.1% in rats supplemented with multivitamin and minerals for the entire study and prevented the colonic tissue from histopathological alterations induced by DMH.     

Paraoxonase (PON1) 55 and 192 polymorphism and its effects to oxidant-antioxidant system in turkish patients with type 2 diabetes mellitus

Paraoxonase (PON1) is a serum enzyme with an antioxidant function, protecting the low density lipoproteins (LDL) from oxidative modifications. Because diabetic patients are at greater risk of oxidative stress, we investigated the effect of PON1 55 methione (M)/leucine (L) and PON1 192 glutamine (A)/arginine (B) polymorphisms on oxidant-antioxidant system in 213 individuals with type 2 diabetes mellitus and 116 non-diabetic control subjects from Turkish population were included in the study. Polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP), and agarose gel electrophoresis techniques were used to determine the PON1 genotypes. Thiobarbituric acid reactive substances (TBARS), conjugated dienes levels in the serum and glutathione (GSH) levels in whole blood were measured spectrophotometrically. In both groups PON1 192 AA and PON1 55 MM genotypes had higher TBARS, conjugated dienes levels and lower GSH levels, whereas PON1 192 BB and PON1 55 LL genotypes had lower TBARS, conjugated diene levels and higher GSH level than other genotypes. We thus conclude that PON1 192 BB and PON1 55 LL alleles have protective effect against oxidative stress.     

Oxidative stress and antioxidant status in mouse kidney: effects of dietary lipid and vitamin E plus iron

The purpose of this study was to determine the effects of dietary fat, vitamin E, and iron on oxidative damage and antioxidant status in kidneys of mice. Sixty 1-month-old male Swiss-Webster mice were fed a basal vitamin E-deficient diet that contained either 8% fish oil + 2% corn oil or 10% lard with or without 1 g all-rac-alpha-tocopherol acetate or 0.74 g ferric citrate per kilogram of diet for 4 weeks. Significantly (P < 0.05) higher levels of lipid peroxidation products, thiobarbituric acid reactants (TBAR), and conjugated dienes were found in the kidneys of mice fed with fish oil compared with mice fed lard irrespective of vitamin E status. Mice maintained on a vitamin E-deficient diet had significantly higher renal levels of TBAR, but not conjugated dienes, than the supplemented group. Fish oil fed mice receiving vitamin E supplementation had lower levels of alpha-tocopherol than did mice in the lard fed group. Significantly higher levels of ascorbic acid were also found in the kidneys of mice fed with fish oil than were found in mice fed lard. The levels of protein carbonyls and glutathione (GSH), and activities of catalase, superoxide dismutase, selenium (Se)-GSH peroxidase, and non-Se-GSH peroxidase were not significantly altered by dietary fat or vitamin E. Dietary iron had no significant effect on any of the oxidative stress and antioxidant indices measured. The results obtained provide experimental evidence for the pro-oxidant effect of high fish oil intake in mouse kidney and suggest that dietary lipids play a key role in determining cellular susceptibility to oxidative stress.     

Antioxidant role of coumarin on streptozotocin-nicotinamide-induced type 2 diabetic rats

The purpose of this study was to investigate the antioxidant role of coumarin on streptozotocin-nicotinamide-induced Type 2 diabetic rats. In experimental rats, the levels of plasma glucose, insulin, and the levels of thiobarbituric acid reactive substances, lipid hydroperoxides, conjugated dienes, and the activities of superoxide dismutase, catalase, glutathione-S-transferase, and glutathione peroxidase were assayed in liver and kidney. Diabetic rats showed elevated levels of plasma glucose and lipid peroxidation markers and reduced plasma insulin and antioxidant enzymes. Oral administration of coumarin resulted in a significant reduction in the plasma glucose and lipid peroxides and a significant increase in the plasma insulin and antioxidant enzymes. Chronic treatment of coumarin remarkably restored the normal status of the histopathological changes observed in the selected tissues. It can be concluded that coumarin has antioxidant effect in Type 2 diabetic rats.     

Impact of Hemidesmus indicus R.Br. extract on ethanol-mediated oxidative damage in rat kidney

Abstract

The antioxidant effect of the ethanolic extract of Hemidesmus indicus R.Br. root (EHI), an indigenous Ayurvedic medicinal plant in India, was studied in rats with ethanol-induced nephrotoxicity. Administering 5 g/kg body weight/day of ethanol for 60 days to male Wistar rats resulted in significantly elevated levels of serum urea, creatinine and uric acid as well as kidney thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (LOOH) and conjugated dienes (CD) as compared to those of the experimental control rats. Decreased levels of kidney superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), vitamin C and vitamin E were also observed on alcohol administration as compared with those of the experimental control rats. EHI was administered at a dose of 500 mg/kg body weight/day for the last 30 days of the experiment to rats with ethanol-induced kidney injury, which significantly decreased the levels of serum urea, uric acid and creatinine as well as kidney TBARS, LOOH and CD and significantly elevated the activities of SOD, CAT, GPx, GSH, vitamin C and vitamin E in kidney as compared to that of untreated ethanol-administered rats. Histopathological observations also correlated with the biochemical parameters. Thus, the data indicate that treatment with EHI offers protection against free radical-mediated oxidative stress in kidney of animals with ethanol-induced nephtrotoxicity.     

Impact of Hemidesmus indicus R.Br. extract on ethanol-mediated oxidative damage in rat kidney

The antioxidant effect of the ethanolic extract of Hemidesmus indicus R.Br. root (EHI), an indigenous Ayurvedic medicinal plant in India, was studied in rats with ethanol-induced nephrotoxicity. Administering 5 g/kg body weight/day of ethanol for 60 days to male Wistar rats resulted in significantly elevated levels of serum urea, creatinine and uric acid as well as kidney thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (LOOH) and conjugated dienes (CD) as compared to those of the experimental control rats. Decreased levels of kidney superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH), vitamin C and vitamin E were also observed on alcohol administration as compared with those of the experimental control rats. EHI was administered at a dose of 500 mg/kg body weight/day for the last 30 days of the experiment to rats with ethanol-induced kidney injury, which significantly decreased the levels of serum urea, uric acid and creatinine as well as kidney TBARS, LOOH and CD and significantly elevated the activities of SOD, CAT, GPx, GSH, vitamin C and vitamin E in kidney as compared to that of untreated ethanol-administered rats. Histopathological observations also correlated with the biochemical parameters. Thus, the data indicate that treatment with EHI offers protection against free radical-mediated oxidative stress in kidney of animals with ethanol-induced nephrotoxicity.     

Antioxidant defenses and lipid peroxidation damage in estivating toads, Scaphiopus couchii

Tissue-specific changes in antioxidant defenses and lipid peroxidation damage were analyzed in spadefoot toads, Scaphiopus couchii, to determine how these responded during estivation, a state of suppressed oxygen consumption. Maximal activities of glutathione-S-transferase, glutathione reductase, glutathione peroxidase, superoxide dismutase and catalase were measured in six organs from 2-month-estivated toads and compared with activities in animals awakened for 10 days after estivation. Activities of many enzymes, particularly the glutathione-linked enzymes, were significantly lower in tissues of estivating toads than in awake toads. This indicates that enzymatic antioxidant defenses are probably modulated in response to the rate of reactive oxygen species generation in tissues, which is proportional to oxygen consumption. Antioxidant enzyme activities were largely insensitive to high urea, which accumulates during estivation, but were inhibited by elevated KCl. Levels of reduced glutathione were also significantly lower in three organs during estivation and all organs, except skeletal muscle, exhibited a higher oxidized/reduced glutathione ratio, indicating a more oxidized state during estivation. Products of lipid peroxidation (conjugated dienes, lipid hydroperoxides) were higher in tissues of estivated than control toads, suggesting accumulated oxidative damage to lipids during dormancy. One enzymatic source of free radical generation, xanthine oxidase, appeared to have little impact because its activity was detectable only in liver and was significantly lower in estivated toads. The data indicate that both enzymatic and metabolite antioxidant defenses in toads are adaptable systems that are modulated in estivating versus awake states. Accepted: 21 October 1997     

Anti-oxidant effects of cinnamon (Cinnamomum verum) bark and greater cardamom (Amomum subulatum) seeds in rats fed high fat diet

In order to gain insight into the antioxidant effect of cinnamon (Cinnamomum verum; Lauraceae) and cardamom (Amomum subulatum; Zingiberaceae) hepatic and cardiac antioxidant enzymes, glutathione (GSH) content and lipid conjugated dienes were studied in rats fed high fat diet along with cinnamon or cardamom. The antioxidant enzyme activities were found to be significantly enhanced whereas GSH content was markedly restored in rats fed a fat diet with spices. In addition, these spices partially counteracted increase in lipid conjugated dienes and hydroperoxides, the primary products of lipid peroxidation. Thus, it appears that these spices exert antioxidant protection through their ability to activate the antioxidant enzymes.     

Protective effect of esculetin on hyperglycemia-mediated oxidative damage in the hepatic and renal tissues of experimental diabetic rats

Diabetes mellitus is the most common serious metabolic disorder and it is considered to be one of the five leading causes of death in the world. Hyperglycemia-mediated oxidative stress plays a crucial role in diabetic complications. Hence, this study was undertaken to evaluate the protective effect of esculetin on the plasma glucose, insulin levels, tissue antioxidant defense system and lipid peroxidative status in streptozotocin-induced diabetic rats. Diabetic rats exhibited increased blood glucose with significant decrease in plasma insulin levels. Extent of oxidative stress was assessed by the elevation in the levels of lipid peroxidation markers such as thiobarbituric acid reactive substances (TBARS), lipid hydroperoxides (HP) and conjugated dienes (CD); reduction in the enzymic antioxidant enzymes like superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST); nonenzymic antioxidants Vitamin C, E and reduced glutathione (GSH) were observed in the liver and kidney tissues of diabetic control rats as compared to control rats. Oral supplementation of esculetin to diabetic rats for 45 days significantly brought back lipid peroxidation markers, enzymic and nonenzymic antioxidants to near normalcy. Moreover, the histological observations evidenced that esculetin effectively rescues the hepatocytes and kidney from hyperglycemia mediated oxidative damage without affecting its cellular function and structural integrity. These findings suggest that esculetin (40 mg/kg BW) treatment exerts a protective effect in diabetes by attenuating hyperglycemia-mediated oxidative stress and antioxidant competence in hepatic and renal tissues. Further, detailed studies are in progress to elucidate the molecular mechanism by which esculetin elicits its modulatory effects in insulin signaling pathway.     

Cerebral antioxidant status and free radical generation following glutathione depletion and subsequent recovery

This study was aimed to evaluate the oxidative damage, production of reactive oxygen species and the status of antioxidative defenses following cerebral GSH depletion induced by two classical depletors, diethylmaleate (DEM, 3 mmol/kg, i.p.) and phorone (PHO, 4 mmol/kg, i.p.). The treatment decreased (40-43%) brain glutathione levels at 2 h, followed by a partial recovery at 24 h. Cerebral glutathione depletion by these agents increased the levels of superoxide anion and hydroxyl radical at both the time intervals; however, hydrogen peroxide was high at 24 h only. It also produced a dramatic increase in the protein carbonyls at 2 h but not at 24h, without any significant effect on lipid peroxidation and conjugated diene levels. These rats showed a significantly lowered superoxide dismutase activity both at 2 h and 24 h of exposure, as compared to controls. Glutathione depletion enhanced catalase activity markedly at 2 h, followed by some recovery at 24 h. While Se-independent glutathione peroxidase (GPx) and glutathione S-transferase activities were increased at both 2 and 24 h time intervals, Se-dependent GPx and glucose-6-phosphate dehydrogenase were induced at 2 h only. Glutathione depletion decreased ceruloplasmin and vitamin E levels significantly at 2 h. However, ascorbic acid remained unaffected. It may be concluded that an acute cerebral glutathione depletion generates higher levels of reactive oxygen species, which may be responsible for oxidative modification of proteins. Some of these changes appear to recover soon after an activation of a variety of cellular antioxidant defense mechanisms and glutathione restoration. It appears that central nervous system is highly vulnerable to oxidative damage following a moderate glutathione depletion that may result from certain diseases or xenobiotic exposures.     

Pro-oxidant and antioxidant processes in gas gland and other tissues of cod (Gadus morhua)

Partial reduction of molecular oxygen produces reactive oxyradicals, including the superoxide anion radical (O _- ² ) and hydroxyl radical (·OH). The gas gland functions under hyperoxic and acidic conditions and therefore is likely to be subjected to enhanced oxidative stress. Aspects of pro- and antioxidant processes in gas gland were compared with other tissues likely to be subject to differing degrees of oxyradical production, viz. liver (site of chemically-mediated oxyradical production), gills and skeletal muscle. Antioxidant enzyme activities (superoxide dismutase, catalase, selenium-dependent and total glutathione peroxidase) per g wet weight were highest in liver and lowest in muscle. Catalase and glutathione peroxidase activies per g wet weight were higher in gills than in gas gland, whereas the reverse was seen for superoxide dismutase. Cytosolic superoxide dismutase activities per mg protein were two- and nine-fold higher in gas gland than in liver and gills. The pH characteristics of the antioxidant enzymes were generally similar in all the tissues. Glutathione, vitamin E and unsaturated (peroxidizable) lipid levels were generally highest in liver followed by gas gland. Lipid peroxidation (malonaldehyde equivalents) was evident in all tissues except gas gland. Hydrogen peroxide and O _- ² were involved in the NAD(P)H-dependent ferric/EDTA-mediated formation of ·OH (as measured by 2-keto-4-methiolbutyrate oxidation) by mitochondrial and postmitochondrial fractions of gas gland. Tissue maximal potentials for ·OH production paralled superoxide dismutase but not catalase or glutathione peroxidase activities. Overall, the results confirm the presence of effective antioxidant defences in gas gland and support previous workers' contentions of a central role for superoxide dismutase in this process.Abbreviations EDTA di-sodium ethylenediaminetetra-acetic acid - G-6-P glucose-6-phosphate - GPX total glutathione peroxidase - GSH reduced glutathione - GSSG oxidised glutathione - GST glutathion-S-transferase - HPLC high performance liquid chromatography - KMBA 2-keto-4-methiolbutyric acid - MOPS 3-[N-morpholino] propane-sulphonic acid - PMS postmitochondrial supernatant - Se-GPX selenium-dependent glutathion peroxidase - SOD superoxide dismutase - TCA trichloroacetic acid     

Hesperidin, a flavanone glycoside, on lipid peroxidation and antioxidant status in experimental myocardial ischemic rats

Myocardial infarction continues to be a leading cause of mortality world-wide. Novel therapies are needed to treat the myocardial ischemia. This study was undertaken to evaluate the cardioprotective role of hesperidin on isoproterenol-induced myocardial ischemia in rats. Myocardial ischemia was induced by subcutaneous injection of isoproterenol hydrochloride (85 mg/kg body weight), for two consecutive days. Isoproterenol-administered rats showed elevated levels of cardiac markers (aspartate transaminase, alanine transaminase, lactate dehydrogenase, creatine kinase, creatine kinase-MB, cardiac troponins T and I) when compared with control and hesperidin treatment groups (100, 200 and 400 mg/kg body weight). The serum levels of cardiac markers were significantly reduced at the doses of 200 mg and 400 mg. All further experiments were carried out at the 200 mg dose. Lipid peroxidation markers (thiobarbituric acid reactive substances, lipid hydroperoxides and conjugated dienes) were elevated significantly in the plasma and heart whereas non-enzymic antioxidants (vitamin C, vitamin E and reduced glutathione) were decreased significantly. Activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and glutathione reductase declined significantly in the heart of ischemic rats. However, after hesperidin treatment, all the above parameters reverted to normal levels. This study demonstrated that the cardioprotective effect of hesperidin on ischemic rats could be due to its anti-lipid peroxidative and antioxidant properties.     

Galangin,a dietary flavonoid,improves antioxidant status and reduces hyperglycemia-mediated oxidative stress in streptozotocin-induced diabetic rats

Objective: To examine the effect of galangin on hyperglycemia-mediated oxidative stress in streptozotocin (STZ)-induced diabetic rats.

Methods: Diabetes was induced by intraperitoneal administration of low-dose STZ (40?mg/kg body weight (BW)) into male albino Wistar rats. Galangin (8?mg/kg BW) or glibenclamide (600?µg/kg BW) was given orally, once daily for 45 days to normal and STZ-induced diabetic rats.

Results: Diabetic rats showed significantly increased levels of plasma glucose, thiobarbituric acid reactive substances, lipid hydroperoxides, and conjugated dienes. The levels of insulin and non-enzymatic antioxidants (vitamin C, vitamin E, reduced glutathione) and the activity of enzymatic antioxidants (superoxide dismutase, catalase, glutathione peroxidase, and glutathione-S-transferase (GST)) were decreased significantly in diabetic control rats. These altered plasma glucose, insulin, lipid peroxidation products, enzymatic and non-enzymatic antioxidants ions were reverted to near-normal level after the administration of galangin and glibenclamide.

Conclusion: The present study shows that galangin decreased oxidative stress and increased antioxidant status in diabetic rats, which may be due to its antidiabetic and antioxidant potential.     

Modulatory effect of sesamol on DOCA-salt-induced oxidative stress in uninephrectomized hypertensive rats

The present study was undertaken to investigate the antihypertensive and antioxidant effects of sesamol on uninephrectomized deoxycorticosterone acetate (DOCA)-salt-induced hypertensive rats. Hypertension was induced in surgically single-kidney-removed (left) adult male albino Wistar rats, weighing 180–200 g, by injecting DOCA (25 mg/kg BW) subcutaneously twice a week for 6 weeks, with saline instead of tap water for drinking. Rats were treated with three different doses of sesamol (50, 100 and 200 mg/kg BW) post-orally by gavage daily for 6 weeks. Hypertension was revealed by increased systolic and diastolic blood pressure and the toxicity of DOCA-salt was determined using hepatic marker enzymes, aspartate aminotransferase, alanine aminotransferase, alkaline phospatase and gamma-glutamyl transpeptidase; and, lipid peroxidative markers, thiobarbituric acid reactive substances, lipid hydroperoxides and conjugated dienes were assayed. The activities of enzymatic antioxidants, superoxide dismutase, catalase and glutathione peroxidase and the levels of non-enzymatic antioxidants (vitamin C, vitamin E and reduced glutathione) were evaluated in erythrocytes, plasma and tissues. Post-oral administration of sesamol at the dosage of 50 mg/kg BW remarkably decreased systolic and diastolic blood pressure, hepatic marker enzyme activities and lipid peroxidation products and also enhanced the antioxidant activity. The biochemical observations were also supported by histopathological examinations of the rat liver, kidney and heart sections. These results suggest that sesamol possesses antihypertensive and antioxidant effects.     

Antihypertensive and antioxidant potential of vanillic acid, a phenolic compound in L-NAME-induced hypertensive rats: a dose-dependence study

We investigated the antihypertensive and antioxidant potential of vanillic acid (VA) in N(ω)-Nitro-L-arginine methyl ester hydrochloride (L-NAME) - treated adult male albino Wistar rats. Treatment of rats with L-NAME (40 mg/kg Bw for 30 days) caused a sustained increase in systolic- (SBP) and diastolic blood pressure (DBP) and significantly decreased the concentration of nitrite/nitrate (NO(x)) in plasma as compared with that in the control. Rats treated with VA restored SBP and DBP to normal level and preserve the plasma NO metabolites concentration. Moreover, VA reduced lipid peroxidation products (thiobarbituric acid reactive substances, lipid hydroperoxides, conjugated dienes) and significantly restored enzymatic antioxidants (superoxide dismutase, catalase, and glutathione peroxidase), non-enzymatic antioxidants (vitamin C, vitamin E, and reduced glutathione) in the plasma. To assess the toxicity if any of VA treatment, hepatic and renal function markers were measured. Our results showed that the effect at a dose of 50 mg/kg Bw of VA was more pronounced than that of the other two doses, 25 and 100 mg/kg Bw. These results were supported by histopathology studies. We conclude that VA possesses an antihypertensive and antioxidant activity in L-NAME-induced hypertensive rats.     

Sulforaphane Restores Cellular Glutathione Levels and Reduces Chronic Periodontitis Neutrophil Hyperactivity In Vitro

The production of high levels of reactive oxygen species by neutrophils is associated with the local and systemic destructive phenotype found in the chronic inflammatory disease periodontitis. In the present study, we investigated the ability of sulforaphane (SFN) to restore cellular glutathione levels and reduce the hyperactivity of circulating neutrophils associated with chronic periodontitis. Using differentiated HL60 cells as a neutrophil model, here we show that generation of extracellular O₂ ^{. -} by the nicotinamide adenine dinucleotide (NADPH) oxidase complex is increased by intracellular glutathione depletion. This may be attributed to the upregulation of thiol regulated acid sphingomyelinase driven lipid raft formation. Intracellular glutathione was also lower in primary neutrophils from periodontitis patients and, consistent with our previous findings, patients neutrophils were hyper-reactive to stimuli. The activity of nuclear factor erythroid-2-related factor 2 (Nrf2), a master regulator of the antioxidant response, is impaired in circulating neutrophils from chronic periodontitis patients. Although patients’ neutrophils exhibit a low reduced glutathione (GSH)/oxidised glutathione (GSSG) ratio and a higher total Nrf2 level, the DNA-binding activity of nuclear Nrf2 remained unchanged relative to healthy controls and had reduced expression of glutamate cysteine ligase catalytic (GCLC), and modifier (GCLM) subunit mRNAs, compared to periodontally healthy subjects neutrophils. Pre-treatment with SFN increased expression of GCLC and GCM, improved intracellular GSH/GSSG ratios and reduced agonist-activated extracellular O₂ ^{. -} production in both dHL60 and primary neutrophils from patients with periodontitis and controls. These findings suggest that a deficiency in Nrf2-dependent pathways may underpin susceptibility to hyper-reactivity in circulating primary neutrophils during chronic periodontitis.