Brain Catalase Research Articles

Oxidative stress and genotoxicity induced by ketorolac on the common carp Cyprinus carpio.

The nonsteroidal anti-inflammatory drug ketorolac is extensively used in the treatment of acute postoperative pain. This pharmaceutical has been found at concentrations of 0.2-60 µg/L in diverse water bodies around the world; however, its effects on aquatic organisms remain unknown. The present study, evaluated the oxidative stress and genotoxicity induced by sublethal concentrations of ketorolac (1 and 60 µg/L) on liver, brain, and blood of the common carp Cyprinus carpio. This toxicant induced oxidative damage (increased lipid peroxidation, hydroperoxide content, and protein carbonyl content) as well as changes in antioxidant status (superoxide dismutase, catalase, and glutathione peroxidase activity) in liver and brain of carp. In blood, ketorolac increased the frequency of micronuclei and is therefore genotoxic for the test species. The effects observed were time and concentration dependent. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1035-1043, 2016.

Effect of persistent and transient hypothyroidism on histoarchitecture and antioxidant defence system in rat brain

The present study reports the effect of 6-n-propylthiouracil (PTU)-induced hypothyroidism on oxidative stress parameter, lipid peroxidation (LPx) and major antioxidant enzyme expressions such as superoxide dismutase (SOD: SOD1 and SOD2) and catalase (CAT) in cerebral cortex rat brain during postnatal persistent (90 days PTU treatment from birth) and transient (30 days PTU treatment from birth followed by PTU withdrawal for 60 days) hypothyroidism. Enhanced level of LPx was observed in transient hypothyroid rats with respect to control and persistent hypothyroid rats. Significantly increased activity of SOD and expression of SOD1 were observed in cerebral cortex of both persistent and transient hypothyroid rats as compared to control. However, unaltered translated level of SOD2 was observed among the groups. Activity of CAT was increased in transient hypothyroid rats, whereas translate level of CAT was increased in both the regions of persistent as well as transient hypothyroidism. The histoarchitecture of cerebral cortex clearly showed a decline in neuronal migration with neurons packed together in both persistent and transient hypothyroid rats as compared to control. These results suggest that deprivation of thyroid hormone modulates redox status and causes oxidative stress in rat brain cerebral cortex during postnatal development and maturation.

Antioxidant activity stimulated by ultraviolet radiation in the nervous system of a crustacean

Ultraviolet (UV) radiation can produce biological damage, principally oxidative stress, by increasing the production of reactive oxygen species (ROS). This study evaluated biochemical impairments related to the oxidative stress induced by UVA, UVB and UVA+UVB (solar simulator-SIM) in environmental doses, during five consecutive days of exposure, in the brain and eyestalk of the crab Ucides cordatus. We evaluated these regions by sampling on the 1st, 3rd and 5th days of UV exposure for lipid peroxidation (LPO), antioxidant capacity against the peroxyl radical (ACAP), and the activities of catalase (CAT), glutathione peroxidase (GPX) and glutathione-S-transferase (GST). Immunohistochemical and immunoblotting assays were performed for anti-activated-caspase 3 in the brains. After the first day of exposure, LPO increased in the eyestalks and brains of the UV-exposed animals; ACAP, and CAT, GPX and GST activities also increased in the brains. On the third day, the LPO values in the eyestalk remained high in the UV-exposed groups, while ACAP decreased in the brain and eyestalk and CAT activity remained high in all irradiated groups in both regions. On the fifth day, LPO decreased in the eyestalk and brain of the UV-exposed groups. These results may have been a consequence of the antioxidant defense system (ADS) activity, since CAT activity was high in both regions, ACAP was high in the eyestalks of the SIM group, and GPX activity remained high in the eyestalks of the UVA and UVB groups. Immunohistochemical assays and immunoblotting showed that there was apoptosis in the brains of the UV-exposed crabs. In conclusion, environmental doses of UV can cause oxidative damage to the CNS cells, including apoptosis.

Effect of some Neuroprotective drugs on certain biochemical parameters during experimental brain ischaemia.

Cerebral ischaemia reperfusion (I/R) triggers a complex series of biochemical events that lead to formation of reactive oxygen species (ROS) and the impairment of enzymatic mechanisms, which result in tissue oxidative stress. This study investigated the effect of some neuroprotective drugs such as vinpocetine, cinnarizine, pyritinol, and rosiglitazone on oxidative stress and cell death biomarkers occurred during experimental brain ischemia/reperfusion injury in rats. Adult male albino Wistar rats were subjected to 1 hr of brain ischaemia followed by reperfusion for 2 hr. Rats were orally treated with aqueous suspension of vinpocetine (3 mg/kg), cinnarizine (7 mg/kg), pyritinol (55 mg/kg), and rosiglitazone (0.5 mg/kg), after 1 hr of ischaemia. Brain superoxide dismutase (SOD), glutathione (GSH), and malondialdhyde (MDA) contents and serum nitric oxide (NO), lactate dehydrogenase (LDH), catalase (CAT), and glucose-6-phosphate dehydrogenase (G6PDH) levels were quantified at the end of the experiment. I/R injury caused a significant decrease in the activity of brain SOD, GSH contents and serum CAT level. It caused a significant increase in serum NO, LDH, G6PDH levels, and brain MDA content in comparison with the sham-operated group. Vinpocetine and rosiglitazone reversed all these biochemical indices. Pyritinol reversed all these biochemical indices except serum NO, and G6PDH. Cinnarizine could not affect brain MDA, serum NO and CAT levels. Both vinpocetine and rosiglitazone may be potent neuroprotective agents against experimental brain I/R injury in rats. Cinnarzine and pyritinol showed a marked neuroprotective activity but less than both drugs.

High-protein diet induces oxidative stress in rat brain: protective action of high-intensity exercise against lipid peroxidation.

It is well established that soy protein diets as well as aerobic exercise could promote antioxidant capacity and consequently reduce free radicals overproduction on brain. However, little is know regarding to the high-protein diets and high intensity exercise on oxidative stress production. The aim of this study was to analyse the effects of high-protein diets and high-intensity exercise (HIE) on brain oxidative stress markers. A total of 40 male Wistar rats were randomly distributed in 4 experimental groups (n=10): normal-protein or high-protein diets with or without HIE for an experimental period of 12 weeks. Main oxidative damage markers in brain such as thiobarbituric acid-reactive substances (TBARs) and protein carbonyl content (PCC) were assessed. In addition, brain manganese superoxide dismutase (Mn-SOD), cooper/ zinc superoxide dismutase (CuZn-SOD) and catalase (CAT) antioxidant enzymes activity, and protein level of Nuclear factor erythroid 2 related factor 2 (Nrf2) were measured. Brain TBARs, PCC, tSOD, Mn-SOD, CuZn-SOD and CAT levels were higher in the high-protein compared to the normal-protein groups (all, p.

The effect of ingested sulfite on visual evoked potentials, lipid peroxidation, and antioxidant status of brain in normal and sulfite oxidase-deficient aged rats.

Sulfite, commonly used as a preservative in foods, beverages, and pharmaceuticals, is a very reactive and potentially toxic molecule which is detoxified by sulfite oxidase (SOX). Changes induced by aging may be exacerbated by exogenous chemicals like sulfite. The aim of this study was to investigate the effects of ingested sulfite on visual evoked potentials (VEPs) and brain antioxidant statuses by measuring superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities. Brain lipid oxidation status was also determined via thiobarbituric acid reactive substances (TBARS) in normal- and SOX-deficient aged rats. Rats do not mimic the sulfite responses seen in humans because of their relatively high SOX activity level. Therefore this study used SOX-deficient rats since they are more appropriate models for studying sulfite toxicity. Forty male Wistar rats aged 24 months were randomly assigned to four groups: control (C), sulfite (S), SOX-deficient (D) and SOX-deficient + sulfite (DS). SOX deficiency was established by feeding rats with low molybdenum (Mo) diet and adding 200 ppm tungsten (W) to their drinking water. Sulfite in the form of sodium metabisulfite (25 mg kg(-1) day(-1)) was given by gavage. Treatment continued for 6 weeks. At the end of the experimental period, flash VEPs were recorded. Hepatic SOX activity was measured to confirm SOX deficiency. SOX-deficient rats had an approximately 10-fold decrease in hepatic SOX activity compared with the normal rats. The activity of SOX in deficient rats was thus in the range of humans. There was no significant difference between control and treated groups in either latence or amplitude of VEP components. Brain SOD, CAT, and GPx activities and brain TBARS levels were similar in all experimental groups compared with the control group. Our results indicate that exogenous administration of sulfite does not affect VEP components and the antioxidant/oxidant status of aged rat brains.

Brain catalase in the streptozotocin-rat model of sporadic Alzheimer’s disease treated with the iron chelator–monoamine oxidase inhibitor, M30

Low intracerebroventricular (icv) doses of streptozotocin (STZ) produce regionally specific brain neurochemical changes in rats that are similar to those found in the brain of patients with sporadic Alzheimer's disease (sAD). Since oxidative stress is thought to be one of the major pathologic processes in sAD, catalase (CAT) activity was estimated in the regional brain tissue of animals treated intracerebroventricularly with STZ and the multitarget iron chelator, antioxidant and MAO-inhibitor M30 [5-(N-methyl-N-propargylaminomethyl)-8-hydroxyquinoline]. Five-day oral pre-treatment of adult male Wistar rats with 10 mg/kg/day M30 dose was followed by a single injection of STZ (1 mg/kg, icv). CAT activity was measured colorimetrically in the hippocampus (HPC), brain stem (BS) and cerebellum (CB) of the control, STZ-, M30- and STZ + M30-treated rats, respectively, 4 weeks after the STZ treatment. STZ-treated rats demonstrated significantly lower CAT activity in all three brain regions in comparison to the controls (p < 0.05 for BS and CB, p < 0.01 for HPC). M30 pre-treatment of the control rats did not influence the CAT activity in HPC and CB, but significantly increased it in BS (p < 0.05). M30 pre-treatment of STZ-treated rats significantly increased CAT activity in the HPC in comparison to the STZ treatment alone (p < 0.05) and normalized to the control values. These findings are in line with the assumption that reactive oxygen species contribute to the pathogenesis of STZ in a rat model of sAD and indicate that multifunctional iron chelators such as M30 might also have beneficial effects in this non-transgenic sAD model.

The renaissance of acetaldehyde as a psychoactive compound: decades in the making.

The renaissance of acetaldehyde as a psychoactive compound: decades in the making.

Modulation of Transient Receptor Potential Vanilloid Subtype 1 (TRPV&lt;sub&gt;1&lt;/sub&gt;) and Norepinephrine Transporters (NET) Protect Against Oxidative Stress, Cellular Injury, and Vascular Dementia

Chronic cerebral hypoperfusion (CCH) is a risk factor for the development of vascular dementia (VaD). CCH participates in a negative role in cognitive impairments. Transient receptor potential vanilloid subtype 1 (TRPV1) participates in cognition, ischemic damage and neuroprotection. Selective norepinephrine transporter (NET) inhibitors have a role in cognitive dysfunction and oxidative stress. The role of TRPV1 and NET in CCH induced VaD is still unknown. The present study has been structured to investigate the role of vanillin; a selective agonist of TRPV1 as well as atomoxetine; a selective NET inhibitor in CCH induced VaD in mice. Permanent bilateral common carotid arteries ligation or two vessel occlusion (2VO) technique was used to induce a stage of chronic cerebral hypoperfusion in mice. 2VO animals have shown significant impairment of locomotion (Actophotometer), motor coordination (Rota rod), learning and memory (Morris water maze). 2VO animals have shown significant reduction in brain catalase, glutathione, and superoxide dismutase, with significant increase in brain infarct size (TTC staining), malondialdehyde and acetyl cholinesterase-AChE activity. Whereas, administration of vanillin as well as atomoxetine has significantly attenuated 2VO induced impaired locomotion, motor coordination, learning and memory, brain damage, brain oxidative stress and higher AChE activity. It may be concluded that 2VO induced CCH has elicited VaD, which was attenuated by vanillin and atomoxetine. Thus, modulators of vanilloid receptors and norepinephrine transporter may be explored further for their benefits in CCH induced VaD.

Induction of brain cytochrome P450 2E1 boosts the locomotor-stimulating effects of ethanol in mice

In the central nervous system ethanol (EtOH) is metabolized into acetaldehyde by different enzymes. Brain catalase accounts for 60% of the total production of EtOH-derived acetaldehyde, whereas cerebral cytochrome P450 2E1 (CYP 2E1) produces 20% of this metabolite. Acetaldehyde formed by the activity of central catalase has been implicated in some of the neurobehavioral properties of EtOH, yet the contribution of CYP 2E1 to the pharmacological actions of this drug has not been investigated. Here we assessed the possible participation of CYP 2E1 in the behavioral effects of EtOH. Thus, we induced CYP 2E1 activity and expression by exposing mice to chronic acetone intake (1% v/v for 10 days) and examined its consequences on the stimulating and uncoordinating effects of EtOH (0–3.2 g/kg) injected intraperitoneally. Our data showed that 24 h after withdrawal of acetone brain expression and activity of CYP 2E1 was induced. Furthermore, the locomotion produced by EtOH was boosted over the same interval of time. Locomotor stimulation produced by amphetamine or tert-butanol was unchanged by previous treatment with acetone. EtOH-induced motor impairment as evaluated in a Rota-Rod apparatus was unaffected by the preceding exposure to acetone. These results indicate that cerebral CYP 2E1 activity could contribute to the locomotor-stimulating effects of EtOH, and therefore we suggest that centrally produced acetaldehyde might be a possible mediator of some EtOH-induced pharmacological effects.

Effect of adipose tissue-derived mesenchymal stem cell treatment on oxidative stress and inflammatory response following Escherichia coli lipopolysaccharide

Stem cells are the focus of extensive experimental and clinical research with the aim of replacing lost or damaged tissues. This paper studies the effect of systemic stem cell injections on the redox status of the brain and liver in a model of systemic inflammatory illness. Mice were treated with intraperitoneal (i.p.) injection of adipose tissue-derived mesenchymal stem cell (AT-MSCs) suspension, or saline at time of lipopolysaccharide (LPS; 200 mg/kg, i.p.) administration and euthanized 4 h later. Results show that the administration of LPS increased the oxidative stress in the brain and liver tissues. Malondialdehyde (MDA) increased by 53 and 68.9 %, reduced glutathione (GSH) decreased by 44.4 and 50.6 %, and nitric oxide increased by 47.7 and 87.2 % in the brain and liver, respectively. Total antioxidant capacity (TAC) decreased by 37.8 and 76.2 %, catalase activity decreased by 58.2 and 29.2 %, and paraoxonase 1 (PON1) activity decreased by 53.1 and 22.5 % in the brain and liver, respectively. In addition, nuclear factor kappa B (NF-κB) and the monocyte chemoattractant protein-1 (MCP-1) increased in the brain and liver, respectively, after endotoxin injection. Mice treated with AT-MSCs showed unchanged MDA, increased brain GSH (45.5 %), TAC (171.1 %), catalase activity (58.4 %), and PON1 activity (110.4 %). In the liver, MDA and catalase activity were unchanged, but TAC decreased by −36.7 % and PON1 activity decreased by −22.8 %. NF-κB decreased in the liver, while MCP-1 decreased in the brain and liver by AT-MSCs treatment. AT-MSCs reduced inflammatory cell infiltration and necrotic damage in the liver and markedly decreased the number of degenerated neurons in the cortex and striatum in LPS-treated mice. Stem cell treatment was associated with lower tumor necrosis factor-alpha (TNF-α), inducible nitric oxide synthase (iNOS), and caspase-3 immunoreactivity in the brain (cortex and striatum) and liver tissues compared to that in the LPS control group. Thus, the systemic administration of AT-MSCs suspension in a model of mild systemic illness modulates the cellular oxidative response and exerts anti-inflammatory effect. AT-MSCs prevent tissue injury via decreased nitric oxide generation due to iNOS expression and decreased activation of caspase-3, TNF-α, and MCP-1.

Protective effects of boron on cyclophosphamide induced lipid peroxidation and genotoxicity in rats

The aim of the present study was to evaluate the possible protective effect of boron (B) on cyclophosphamide (CYC) induced oxidative stress in rats. Totally, thirty Wistar albino male rats were fed standard rodent diet and divided into 5 equal groups: physiological saline was given intraperitoneally (i.p.) to the control group (vehicle treated), to the second group only 75mgkg−1 CYC was given i.p. on the 14th d, and boron was administered (5, 10, and 20mgkg−1, i.p.) to the other groups for 14 d and CYC (75mgkg−1, i.p.) on the 14th d. CYC caused increase of malondialdehyde and decrease of glutathione levels, decrease of superoxide dismutase activities in erythrocyte and tissues, decrease of erythrocyte, heart, lung, and brain catalase, and plasma antioxidant activities. Also, CYC treatment caused to DNA damage in mononuclear leukocytes. Moreover, B exhibited protective action against the CYC-induced histopathological changes in tissues. However, treatment of B decreased severity of CYC-induced lipid peroxidation and genotoxicity on tissues. In conclusion, B has ameliorative effects against CYC-induced lipid peroxidation and genotoxicity by enhancing antioxidant defence mechanism in rat.

Antidepressant-like activity of beta-carotene in unstressed and chronic unpredictable mild stressed mice

The antidepressant-like activity of beta-carotene in Swiss young male albino mice subjected to chronic unpredictable mild stress was evaluated. Beta-carotene (50 and 100mg/kg, p.o.) and imipramine (15mg/kg, p.o.) per se were administered for 21 successive days to separate groups of unstressed and stressed mice. Higher dose (100mg/kg) of beta-carotene and imipramine significantly decreased immobility period of mice in tail suspension test. These compounds significantly restored the reduced sucrose preference in stressed mice. There was no significant effect on locomotor activity of mice by the drugs. Beta-carotene significantly reversed stress-induced increase in brain catalase, monoamine oxidase (MAO-A), thiobarbituric acid-reactive substances (TBARS); and plasma nitrite and corticosterone levels; and increased stress-induced decrease in reduced glutathione levels. Thus, beta-carotene showed significant antidepressant-like activity in unstressed and stressed mice probably through inhibition of MAO-A and oxidative stress. Its antidepressant-like activity in stressed mice might also be due to decrease in plasma corticosterone levels.

Possible involvement of nitric oxide mechanism in the neuroprotective effect of rutin against immobilization stress induced anxiety like behaviour, oxidative damage in mice

Dietary supplements are widely used to manage stress and related consequences. However, the exact pathological mechanism and cellular cascades involved in the action of these supplements are not properly understood so far. Therefore, the present study has been designed to explore the neuroprotective mechanism of rutin against immobilization stress-induced anxiety-like behavioural and oxidative damage in mice. Laboratory Animal Centre A-strain (laca) mice were used in the present study. Rutin (20, 40, and 80mg/kg), l-arginine (100mg/kg), l-nitroarginine methyl ester (l-NAME) (5mg/kg) and vitamin-E (50mg/kg) were administered for 5 days before 6h immobilization stress on 6th day. Various behavioural parameters (mirror chamber test, locomotor activity) followed by biochemical parameters (lipid peroxidation, nitrite concentration, reduced glutathione and catalase) in brain and then serum corticosterone level were assessed. 6h immobilization stress produced anxiety-like behavioural in mirror chamber test, raised corticosterone level and oxidative stress (as evidenced by rise in lipid peroxidation, nitrite concentration, depletion of reduced glutathione and catalase activity) significantly as compared to naive group. 5 days pre-treatment with rutin (40 and 80mg/kg) causes a significant attenuation of locomotor activity, corticosterone level, oxidative stress as compared to control. Further, l-arginine (100mg/kg) pre-treatment significantly reversed the protective effect of rutin (40mg/kg) in 6h immobilized animals. However, l-NAME (5mg/kg) pre-treatment with rutin (40mg/kg) potentiated their protective effect which was significant as compared to their effect per se. The present study suggests the involvement of nitric oxide mechanism in the neuroprotective effect of rutin against immobilization stress-induced anxiety-like behaviour and oxidative damage in mice.

Behavioral and biochemical evidences for antidepressant-like activity of palmatine in mice subjected to chronic unpredictable mild stress

BackgroundIn the present study, antidepressant-like activity of palmatine was evaluated in unstressed and stressed young male Swiss albino mice. MethodsThe animals were subjected to unpredictable mild stress daily for 21 successive days to induce depression-like behavior. Palmatine (0.25, 0.5, 1mg/kg, ip) was administered for 21 successive days to unstressed and stressed mice. The antidepressant-like activity was evaluated using the tail suspension test, forced swim test and sucrose preference test. ResultsPalmatine (0.5 and 1mg/kg, ip) significantly decreased immobility periods of unstressed and stressed mice in the forced swim test and tail suspension test, thus indicating its significant antidepressant-like activity. Only the highest dose (1mg/kg) of palmatine significantly reversed the stress-induced decrease in sucrose preference. There was no significant effect on locomotor activity of the mice by palmatine and fluoxetine. The antidepressant-like activity of palmatine was found to be comparable to fluoxetine (10mg/kg) administered for successive 21 days. Palmatine (0.5 and 1mg/kg, ip) significantly reversed the stress-induced increase in brain catalase levels, MAO-A activity, lipid peroxidation, plasma nitrite and corticosterone levels. ConclusionsPalmatine showed significant antidepressant-like activity in unstressed and stressed mice probably through inhibition of MAO-A activity, decrease in plasma nitrite levels and due to its antioxidant activity. In addition, palmatine also showed antidepressant-like activity in stressed mice probably through decrease in plasma corticosterone levels.

Neuro, cardio, and reno protective activities of rosuvastatin in streptozotocin-induced type 2 diabetic rats undergoing treatment with metformin and glimepiride.

Diabetes is associated with complications like neuropathy, nephropathy, cardiomyopathy, and retinopathy due to increased oxidative stress and serum lipids. In the present study, rosuvastatin, a HMG-CoA inhibitor, was investigated for its protective effect in neuropathy, nephropathy, and cardiomyopathy based on the lipid-lowering property along with its pleiotropic effects such as improved blood flow to the organ and antioxidant defense. Type 2 diabetes was induced in Wistar rats by single i.p. administration of streptozotocin (50 mg/kg). These diabetic rats were treated with daily doses of rosuvastatin (10 mg/kg) alone, metformin (120 mg/kg) and glimepiride (1 mg/kg) and rosuvastatin in combination with metformin (120 mg/kg) and glimepiride (1 mg/kg) for a period of 6 weeks. The biochemical parameters involved in neuropathy, renopathy, and cardiopathy were estimated. Treatment resulted in significant (P < 0.05) decrease in thiobarbituric acid reactive substances (TBARS) and increase in levels of glutathione peroxidise and catalase in brain and kidney homogenates. Significant (P < 0.05) increase in high-density lipoproteins and decrease in creatinine kinase, triglycerides, total serum cholesterol represents the cardioprotective action, whereas significant (P < 0.05) increase in the latency in the hotplate model shows the neuroprotective activity, and significant (P < 0.05) decrease in blood urea nitrogen, creatinine levels and increase in serum total protein levels suggested the renoprotective actions. The unique properties of rosuvastatin such as antioxidant defense and lipid-lowering nature might have resulted in cardio, neuro, and renoprotective activity in type 2 diabetic rats treated with metformin and glimepiride.

Neurotoxic effect of cypermethrin and protective role of resveratrol in Wistar rats

Background: Cypermethrin is a synthetic pyrethroid commonly used in agriculture, veterinary, and household insects/pests management. Resveratrol a polyphenolic phytoalexin abundantly found in grapes and red wine is a potent antioxidant and cytoprotective agent. Objectives: Neurotoxicity of cypermethrin is well-known. The aim of this study was to evaluate neurotoxic effects of cypermethrin and protective role of resveratrol in Wistar rats. Materials and Methods: Thirty male Wistar rats were divided into five groups. Group A served as control. Rats of Group B were treated with cypermethrin at the dose of 3.83 mg/kg body weight (bw) for 7 days. Group C and D were post- and pretreatment of resveratrol (20 mg/kg bw) along with cypermethrin exposure. In Group E, resveratrol served as control. Results: Cypermethrin treated group showed elevation in lipid peroxidation (LPO 83.99%) and inhibition in glutathione (GSH 12.81%), superoxide dismutase (SOD 17.08%), catalase (CAT 11.51%), glutathione-S-transferase (GST 12.12%), glutathione reductase (GR 77.55%), glutathione peroxidase (GPX 23.78 %), total protein (42.95%), and acetylcholinesterase (AChE) activity (47.64%) in rat brain. Posttreatment, pretreatment, and treatment with resveratrol reversed the toxic effect induced by cypermethrin. Conclusion: Our findings strongly suggest that cypermethrin-induced neurotoxicity may be mediated through free radical formation, reduced antioxidant defense mechanism, and inhibition of acetylcholinestrase (AChE) activity. Cypermethrin may be showing AChE inhibitory activity by interacting with the anionic substrate binding site. Administration of resveratrol increased AChE activity and ameliorated cypermethrin-induced brain damage in Wistar rats.

Milk lipids and sardine oil intake modulate differently enzymatic antioxidant defense in rats fed an atherogenic diet

Objective: The effect of milk lipids compared to sardine oil on antioxidant enzymes activities was evaluated in rats fed an atherogenic diet. Methods: Male Wistar rats were divided into three groups (n = 8 for each). Two experimental groups received a 20% casein diet combined with 5% milk lipids or sardine oil and 1% cholesterol for 4 weeks. The control group was fed a standard diet without cholesterol. Results: In red blood cells, superoxide dismutase (SOD) activity was 1.4- and 1.3-fold higher in the milk lipids group compared to the sardine oil and control groups, respectively. In tissues, SOD activity was respectively 2.5- and 1.8-fold lower in heart and aorta, but 1.2- fold higher in liver of rats fed milk lipids compared to those fed sardine oil. In milk lipids group, liver glutathione reductase (GR) and catalase (CAT) activities were respectively 2.5- and 1.2- fold lower compared to sardine oil group. In contrast, liver and heart glutathione peroxidase (GSH-Px) activities were respectively 1.2- and 2.3-fold higher. In aorta, milk lipids decreased SOD, GR, GSH-Px, and CAT activities and the values were respectively 1.8-, 1.7-, 1.2- and 1.5-fold lower than those found in the sardine oil group. Brain GSH-Px and CAT activities were respectively increased by 1.2- and 1.9-fold in the milk lipids group compared with the sardine oil. Milk lipids improved lecithin:cholesterol acyltransferase (LCAT) activity (2.5-fold) when compared with sardine oil. However, serum paraoxonase (PON)1 activity was 2-fold lower in milk lipids group vs control whereas, compared with the sardine oil group, PON1 activity had a tendency to decrease, but not significantly. Conclusion: This study shows that milk lipids and sardine oil intake modulate differently enzymatic antioxidant defense in hypercholesterolemic rats. Milk lipids improve reverse cholesterol transport from peripheral tissues to the liver by enhancing LCAT activity, leading to anti-atherogenic effects.

Pharmacological modulation of I1-imidazoline and α2-adrenoceptors in sub acute brain ischemia induced vascular dementia

Sub-acute brain ischemia is a risk factor for the development of vascular dementia (VaD). Sub-acute brain ischemia induced VaD, participates in a negative role in impaired cognition. Imidazoline receptors are widely expressed in the central nervous system. But the role of I1-imidazoline and α2-adrenoceptors in VaD are still unknown. The present study has been designed to investigate the role of selective I1-imidazoline receptor modulator; moxonidine as well as α2-adrenoceptor modulator; clonidine in sub-acute brain ischemia induced VaD in mice (n=8). Permanent bilateral common carotid arteries ligation (2VO) technique was used to induce sub-acute brain ischemia in mice. Assessment of spatial learning and memory was done by using Morris water maze. Brain damage was assessed as percent infarct, using TTC staining of brain coronal sections. Oxidative stress was assessed by estimating brain malondialdehyde (MDA), catalase (CAT), glutathione (GSH) and superoxide dismutase (SOD). Cholinergic status was assessed by brain acetylcholinesterase (AChE) activity. 2VO animals have shown significant reduction in learning and memory as well as brain CAT, GSH and SOD, with significant increase in brain infarct size, MDA and AChE activity. Whereas, administration of moxonidine and clonidine significantly attenuated 2VO induced learning and memory deficits, brain damage, brain oxidative stress and higher AChE activity. It may be concluded that 2VO induced sub-acute brain ischemia has elicited dementia, which was attenuated by moxonidine and clonidine. Thus, modulators of I1-imidazoline receptors may be explored further for their benefits in sub-acute brain ischemia induced vascular dementia.

Protective effects of caffeic acid phenethyl ester on ifosfamide-induced central neurotoxicity in rats

The aim of this study was to establish the protective effect of caffeic acid phenethyl ester (CAPE) against the ifosfamide (IFOS)-induced central neurotoxicity in rats and to determine the changes in oxidant-antioxidant status of brain tissue. A total of 35 Wistar rats (aged 7-12 days) were used in the experiments. The study comprised of five groups. Control untreated rats (n = 7) belonged to group 1; group 2 was given intraperitoneal (IP) injection of CAPE alone (10 µmol/kg; n = 7); group 3 was treated with single IP injection of IFOS (500 mg/kg; n = 7); group 4 was treated for 2 days with IP administration of CAPE (10 µmol/kg) beginning from one day before single IP injection of IFOS (n = 7); and group 5 was treated with saline and 10% ethanol. At the 24th hour of IFOS treatment, brain tissues were removed for analysis. The brain catalase activity was lower in IFOS group than the other groups (p < 0.05). The levels of malondialdehyde (MDA) and protein carbonyl content in brain tissue were higher in IFOS group than the control, CAPE, ethanol, and IFOS + CAPE groups (p < 0.05). There was no significant difference between MDA and protein carbonyl content of control, CAPE, ethanol, and IFOS + CAPE groups. Immunohistochemistry showed marked activation of caspase 3 in the IFOS group at 24 h after treatment. This study revealed that pretreatment with CAPE might protect brain tissue against IFOS-induced central neurotoxicity. CAPE could be an effective course of therapy to enhance therapeutic efficacy and to lessen IFOS toxicity in clinical chemotherapy.