Brain Lipid Peroxidation Research Articles

Biochemical markers to the protective effects of Fructus Piperis Longi extract on Hepatic encephalopathy in rats

The present study was designed to elucidate the protective effect of subsequent pretreatment withFructus Piperis Longi extract in liver and brain tissue of experimental rats exposed to Hepaticencephalopathy induced by intraperitoneal administration of TAA. Plf extract (50 mg/kg) was force-fedto rats every day, 7 days before administration of Thioacetamide. Thioacetamide 200 mg/kg wasintraperitoneally administered to rats twice per week for four weeks. Administration of Plfext wasextended during Thioacetamide. After 4 weeks, animals were sacrificed. Biochemical parameters inserum and homogenized liver and brain were tested. A significant increase in serum transglutaminase,alkaline phosphatase and gamma glutamyl transferase activity and plasma ammonia, a significantdecrease in serum albumin and total protein was recorded in the liver of Thioacetamide-treated rats.Significant increases in liver and brain lipid peroxides associated to significant decreases of liver andbrain reduced glutathione concentration and catalase activities were also recorded. Administration ofPlfext treatment reduced the severity of liver fibrosis and oxidative damage which was substantiated byimprovement of liver function detected by a decrease in serum aspartate amino transaminase, alanineaminotransferase, alkaline phosphatase, gamma glutamyl transferase activities and increase in totalprotein and Albumin. It was concluded that treatment of the ethanolic extract of Fructus Piperis Longienhance Liver and brain parameter and enhanced antioxidant activities of liver and brain.

Interactions between cadmium and decabrominated diphenyl ethers for the effect on lipid peroxidation in brain of Wistar rats

Interactions between cadmium and decabrominated diphenyl ethers for the effect on lipid peroxidation in brain of Wistar rats

Erythropoietin in the treatment of carbon monoxide neurotoxicity in rat

Erythropoietin (EPO) plays a critical role in the development of the nervous system. In this study, the effects of EPO in carbon monoxide (CO) neurotoxicity were examined. Rats were exposed to 3000 ppm CO for 1 h and then different doses of EPO were administrated intraperitoneally. After 24 h, glial fibrillary acidic protein (GFAP) levels in the serum were determined and water content of brain and the extravasation of a tracer (Evans blue) were measured. Brain lipid peroxidation, myeloperoxidase activity Myelin basic protein (MBP) and BAX/BcL2 protein relative expressions were determined. Cation exchange chromatography was used to evaluate MBP alterations. Seven days after exposure, pathological assessment was performed after Klüver–Barrera staining. EPO reduced malondialdehyde levels at all doses (2500, 5000 and 10,000 u/kg). Lower doses of EPO (625, 1250, 2500 u/kg) significantly decreased the elevated serum levels of GFAP. EPO could not reduce the water content of the edematous poisoned brains. However, at 5000 and 10,000 u/kg it protected the blood brain barrier against integrity loss as a result of CO. EPO could significantly decrease the MPO activity. CO-mediated oxidative stress caused chemical alterations in MBP and EPO could partially prevent these biochemical changes. Fewer vacuoles and demyelinated fibers were found in the EPO-treated animals. EPO (5000 u/kg) could restore the MBP density. CO increased brain BAX/Bcl-2 ratio 38.78%. EPO reduced it 38.86%. These results reveal that EPO could relatively prevent different pathways of neurotoxicity by CO poisoning and thus has the potential to be used as a novel approach to manage this poisoning.

Emilia coccinae (SIMS) G Extract improves memory impairment, cholinergic dysfunction, and oxidative stress damage in scopolamine-treated rats.

BackgroundE. coccinae (SIMS) G. (Asteraceae) is an annual plant commonly found throughout the plain of the Central Africa and widely used in Cameroonian folk medicine for the treatment of fever and convulsions in children. We previously reported that the methanolic extract of this plant improved spatial memory. However no underlying mechanism was explored. The present study was undertaken to investigate the effects of the hydroalcoholic extract of Emilia coccinae on memory in scopolamine treated rats and to propose possible mechanisms of action.MethodsNovel object recognition and Y-maze paradigm were used to test memory while oxidative profile, AChE and ACh level of the whole brain were assessed to outline the mechanism of nootropic activity of the extract. 200 and 400 mg/kg of the extract were chronically administrated during 14 consecutive days in separate groups of scopolamine intraperitoneal treated rats (1.5 mg/kg).ResultsThe hydroalcoholic extract of Emilia coccinae (HEEC) at the dose of 200 mg/kg significantly improved the memory of rats and reversed the amnesia induced by scopolamine. In addition, we showed that this extract is decreasing the acetyl cholinesterase activity while also increasing the acetylcholine levels in the brain. HEEC (200 and 400 mg/kg) significantly increased antioxidant enzyme activities (SOD, GSH and CAT) and reduced lipid peroxidation (MDA level) in the rat whole brain homogenates.ConclusionsTaken together, our results suggested that the hydroalcoholic extract of Emilia coccinae ameliorated the cognitive dysfunction in scopolamine treated rats through the blockage of the oxidative effect of scopolamine and inhibition of AChE activity.

Effect of piracetam, vincamine, vinpocetine, and donepezil on oxidative stress and neurodegeneration induced by aluminum chloride in rats

In this study, we investigated the effects of the memory-enhancing drugs piracetam, vincamine, and vinpocetine or the cholinesterase inhibitor donepezil on the development of oxidative stress, inflammation, and brain damage induced in rat brain by aluminum chloride (AlCl3). Saline (control), piracetam (100 or 300 mg/kg), vincamine (10 or 20 mg/kg), vinpocetine (10 or 20 mg/kg), piracetam 100 mg/kg plus vincamine 10 mg/kg, piracetam 100 mg/kg plus vinpocetine 10 mg/kg, or donepezil 5 mg/kg were administered once daily intraperitoneally for 45 days along with AlCl3 (10 mg/kg, intraperitoneally). Malondialdehyde (MDA), reduced glutathione (GSH), nitric oxide, acetylcholinesterase (AChE), butrylcholinesterase (BChE), paraoxonase (PON1) activities, and prostaglandin E2 (PGE2) concentrations were measured in brain. Histopathology and caspase-3 immunohistochemistry (an apoptotic marker) were also performed. Results indicated that (1) compared to controls, injection of AlCl3 significantly increased brain lipid peroxidation (MDA) and nitric oxide concentrations together with decreased GSH concentrations. PON1 activity in brain was significantly decreased, while AChE and BChE activities were significantly increased compared to control animals. Cortical atrophy, neuronal shrinkage, red neurons, surrounded by vacuolations with cytoplasmic neurofibrillary tangles, intense caspase-3 expression in degenerated neurons, and amyloid deposition were observed; (2) in AlCl3-treated rats, (i) lipid peroxidation was significantly decreased by the lower doses of piracetam, vincamine, and vinpocetine as well as by piracetam plus either vincamine or vinpocetine; (ii) nitric oxide was significantly decreased by the lower doses of piracetam, and vinpocetine, by both doses of vincamine, and by piracetam plus either vincamine or vinpocetine; (iii) nitric oxide also showed significant decrease after treatment with donepezil; (iv) both GSH and PON1 activity showed significant increase following the administration of the test drugs; (v) PGE2 significantly increased by the higher dose of piracetam, vincamine, vinpocetine, and piracetam plus either vincamine or vinpocetine; (vi) AChE and BChE activities decreased after treatment with the lower dose of piracetam, vinpocetine, and piracetam plus either vincamine or vinpocetine; (vii) AChE activity decreased following 20 mg/kg vincamine, and BChE activity decreased following 10 mg/kg vincamine; (viii) AChE but not BChE activity decreased after donepezil; (ix) on histopathology, the low dose of singly used drugs and donepezil had the best improvement in neuronal look, cortical thickness, and degree of vascular congestion. Rats treated with 10 mg/kg vinpocetine showed decreased capsase-3 immunoreactivity in brain and regenerating neurons. These results suggest that while the low therapeutic doses of the nootropic drugs piracetam, vincamine, and vinpocetine display anti-oxidant and neuroptotective effects, their high doses are likely to have prooxidant and proinflammatory properties.

Local salt substitutes “Obu-otoyo” activate acetylcholinesterase and butyrylcholinesterase and induce lipid peroxidation in rat brain

Evidence has shown that ingestion of heavy metals can lead to neurodegenerative diseases. This study aimed to investigate the neurotoxic potential of salt substitutes (Obu-Otoyo); salt A (made by burning palm kernel shaft then soaked in water overnight and the extract from the resulting residue is used as the salt substitute) and salt B (an unrefined salt mined from a local site at Ilobu town, Osun-State, Nigeria) by assessing their effect on some key enzymes linked with neurodegenerative disease [acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities] as well as on malondialdehyde (MDA) content of the rat brain. Salt substitutes were fed to normal rats as dietary inclusion at doses of 0.5 and 1.0% for 30 days. Thereafter, the effect of the salt substitutes on AChE and BChE activities as well as on MDA level in the rat brain was determined. The results revealed that the salt substitutes caused a significant (p<0.05) increase in both AChE and BChE activity and also induced lipid peroxidation in the brain of rats in vivo as well as under in vitro condition in a dose-dependent manner. The effect of the salt substitutes on AChE and BChE activities could be attributed to the presence of some toxic heavy metals. Therefore, the ability of the salt substitutes to induce lipid peroxidation and activate AChE and BChE activities could provide some possible mechanism for their neurotoxic effect.

Free radical scavenging in vitro and biological activity of diphenyl diselenide-loaded nanocapsules: DPDS-NCS antioxidant and toxicological effects.

Selenium compounds, such as diphenyl diselenide (DPDS), have been shown to exhibit biological activity, including antioxidant effects. However, the use of DPDS in pharmacology is limited due to in vivo pro-oxidative effects. In addition, studies have shown that DPDS-loaded nanocapsules (DPDS-NCS) have greater bioavailability than free DPDS in mice. Accordingly, the aim of this study was to investigate the antioxidant properties of DPDS-NCS in vitro and biological activity in mice. Our in vitro results suggested that DPDS-NCS significantly reduced the production of reactive oxygen species and Fe(II)-induced lipid peroxidation (LPO) in brain. The administration of DPDS-NCS did not result in death or change the levels of endogenous reduced or oxidized glutathione after 72 hours of exposure. Moreover, ex vivo assays demonstrated that DPDS-NCS significantly decreased the LPO and reactive oxygen species levels in the brain. In addition, the highest dose of DPDS-NCS significantly reduced Fe(II)- and sodium nitroprusside-induced LPO in the brain and Fe(II)-induced LPO in the liver. Also, δ-aminolevulinate acid dehydratase within the brain was inhibited only in the highest dose of DPDS-NCS. In conclusion, our data demonstrated that DPDS-NCS exhibited low toxicity in mice and have significant antioxidant characteristics, indicating that nanoencapsulation is a safer method of DPDS administration.

Melatonin and selenium reduce plasma cytokine and brain oxidative stress levels in diabetic rats

Background: Hyperglycaemia-induced progression of brain and erythrocyte oxidative injuries might be modulated by melatonin and selenium as potent antioxidants. The present study was conducted to explore whether melatonin and selenium protect against diabetic brain and erythrocyte oxidative stress levels in streptozotocin (STZ)-induced diabetic rats.Materials and methods: Seventy rats were equally divided into seven groups. The first and second groups were used as untreated and placebo treated controls. The third group was treated with STZ to induce diabetes. The fourth and sixth groups received 10 mg kg−1 melatonin. The fifth and seventh groups were treated with 1.5 mg kg−1 selenium (sodium selenite). The sixth and seventh groups were treated with STZ administered with melatonin and selenium as described for the fourth and fifth groups.Results: Brain and erythrocyte lipid peroxidation levels and plasma IL-1β and IL-4 levels were high in the STZ group, although they were low in melatonin and selenium treatments. Decreased glutathione peroxidase, reduced glutathione, total antioxidant status, vitamins A and vitamin E values in brain and erythrocyte of STZ group were increased by melatonin and selenium treatments.Discussion: Melatonin and selenium induced protective effects against diabetes-induced brain and erythrocyte oxidative injuries through regulation of the antioxidant level and cytokine production.

Neuroprotective mechanism of losartan and its interaction with nimesulide against chronic fatigue stress.

Potential role of angiotensin-II and cyclooxygenase have been suggested in the pathophysiology of chronic fatigue stress. The present study has been designed to evaluate the neuroprotective effect of losartan and its interaction with nimesulide against chronic fatigue stress and related complications in mice. In the present study, male Laca mice (20-30 g) were subjected to running wheel activity test session (RWATS) for 6 min daily for 21 days. Losartan, nimesulide and their combinations were administered daily for 21 days, 45 min before being subjected to RWATS. Various behavioral and biochemical and neuroinflammatory mediators were assessed subsequently. 21 days RWATS treatment significantly decreased number of wheel rotations/6 min indicating fatigue stress like behaviors as compared to naive group. 21 days treatment with losartan (10 and 20 mg/kg, ip), nimesulide (5 and 10 mg/kg, po) and their combinations significantly improved behavior [increased number of wheel rotations, reversal of post-exercise fatigue, locomotor activity, antianxiety-like behavior (number of entries, latency to enter and time spent in mirror chamber), and memory performance (transfer latency in plus-maze performance task)], biochemical parameters (reduced serum corticosterone, brain lipid peroxidation, nitrite concentration, acetylcholinesterase activity, restored reduced glutathione levels and catalase activity) as compared to RWATS control. Besides, TNF-α, CRP levels were significantly attenuated by these drugs and their combinations as compared to control. The present study highlights the role of cyclooxygenase modulation in the neuroprotective effect of losartan against chronic fatigue stress-induced behavioral, biochemical and cellular alterations in mice.

Olive oil-enriched diet reduces brain oxidative damages and ameliorates neurotrophic factor gene expression in different life stages of rats

Our aim was to assess the influence of maternal diet rich in monounsaturated fatty acids on oxidative and molecular parameters in brains of mouse pups as well as their body weight during their lifetime. Female rats received a diet containing 20% of olive oil-enriched diet (OOED) and a standard diet control diet (CD) in different periods: pregnancy, lactation and after weaning until pups' adulthood. On the last prenatal day (Group 1), embryos from OOED group showed smaller body weight, brain weight and lower levels of sulphydryl groups glutathione reduced (GSH) in the brain. On postnatal delay-21 (PND21) (Group 2), pups from OOED group showed higher body weight and brain weight, reduced brain weight/body weight ratio and lower brain lipid peroxidation (LP). On PND70 (Group 3), pups from OOED group showed lower brain LP and higher levels of GSH in prefrontal cortex and lower brain levels of reactive species in the hippocampus. Interestingly, the group of animals whose diet was modified from OOED to CD on PND21 showed greater weight gain compared to the group that remained in the same original diet (OOED) until adulthood. Furthermore, OOED consumption during pregnancy and lactation significantly increased BDNF only, as well as its main transcripts exon IV and VI mRNA levels in the prefrontal cortex. In addition, OOED significantly up-regulated FGF-2 mRNA levels in the prefrontal cortex. These findings open a pioneering line of investigation about dietary adjunctive therapeutic strategies and the potential of healthy dietary habits to prevent neonatal conditions and their influence on adulthood.

Arsenic induced oxidative stress and mitochondrial dysfunction in rat brain

The present study was undertaken to reveal the effects of chronic arsenic exposure (25ppm intragastrically for 12 weeks) on mitochondrial functions and oxidative stress in male Wister rats. Chronic arsenic exposure resulted in decrease in the activities of the mitochondrial complexes. There was increased generation of ROS followed by decrease in MnSOD activity. The generation of oxidative stress was associated with increased protein oxidation and lipid peroxidation in rat brain as evident by FTIR spectra. The RT-PCR analysis of NRF 1, NRF 2 and PGC 1α revealed decrease in gene expression suggesting decreased biogenesis following chronic exposure in rat brain. Thus, the findings of the present study reveal that arsenic induced decrease in mitochondrial biogenesis may be responsible for the decreased metabolic response that may be further involved in the generation of oxidative stress and neurodegeneration in rat brain.

Influence of electromagnetic field (1800 MHz) on lipid peroxidation in brain, blood, liver and kidney in rats.

The aim of this study is the evaluation of the influence of repeated (5 times for 15 min) exposure to electromagnetic field (EMF) of 1800 MHz frequency on tissue lipid peroxidation (LPO) both in normal and inflammatory state, combined with analgesic treatment. The concentration of malondialdehyde (MDA) as the end-product of the lipid peroxidation (LPO) was estimated in blood, liver, kidneys, and brain of Wistar rats, both healthy and those with complete Freund's adjuvant (CFA)-induced persistent paw inflammation. The slightly elevated levels of the MDA in blood, kidney, and brain were observed among healthy rats in electromagnetic field (EMF)-exposed groups, treated with tramadol (TRAM/EMF and exposed to the EMF). The malondialdehyde remained at the same level in the liver in all investigated groups: the control group (CON), the exposed group (EMF), treated with tramadol (TRAM) as well as exposed to and treated with tramadol (TRAM/EMF). In the group of animals treated with the complete Freund's adjuvant (CFA) we also observed slightly increased values of the MDA in the case of the control group (CON) and the exposed groups (EMF and TRAM/EMF). The MDA values concerning kidneys remained at the same levels in the control, exposed, and not-exposed group treated with tramadol. Results for healthy rats and animals with inflammation did not differ significantly. The electromagnetic field exposure (EMF), applied in the repeated manner together with opioid drug tramadol (TRAM), slightly enhanced lipid peroxidation level in brain, blood, and kidneys.

Effect of anthocyanins from rabbit-eye blueberry (Vaccinium virgatum) on cognitive function in mice under trimethyltin-induced neurotoxicity

Extracts of rabbit-eye blueberries (Vaccinium virgatum) were investigated for in vitro neuroprotective and in vivo learning and memory effects in mice under trimethyltin (TMT)-induced neurotoxicity. Blueberry anthocyanins showed high in vitro antioxidant activities in ABTS and 2’,7’-dichlorofluorescein diacetate (DCF-DA) assays. In a cell viability assay using MTT, anthocyanins showed protective effects, and lactate dehydrogenase release into the medium was effectively inhibited. Drug-induced cognitive deficits, examined in vivo using Y-maze and passive avoidance testing, were ameliorated by the anthocyanin fraction. HPLC analysis showed that delphinidin was the predominant anthocyanin. After behavioral testing, acetylcholinesterase (AChE) activities and lipid peroxidation in the mouse brain were investigated for biochemical changes. Administration of blueberry anthocyanins reduced the level of TMT-induced memory injury via inhibition of the AChE activity and lipid peroxidation.

Antioxidant properties of Elaeagnus umbellata berry solvent extracts against lipid peroxidation in mice brain and liver tissues

Elaeagnus umbellata is a plant that grows in the hilly areas of Pakistan. Free radical scavenging activities and anti-lipid peroxidative properties of hot water, methanol, n-hexane, and acetone extracts of E. umbellata berries were evaluated. Extracts showed inhibition against thiobarbituric acid reactive species (TBARS) induced using the pro-oxidants iron (10 μM FeSO4) and sodium nitroprusside (5 μM) in brain and liver homogenates of mice. Extracts also showed metal chelating activities of IC50 (extract concentration that causes 50% scavenging)=40–43 μg/mL and DPPH radical scavenging activities of IC50=45.4–49 μg/mL. HPLC analysis revealed the presence of gallic, vanillic, coumaric, ferulic, sinapic, and caffeic acids in berries. The fruit of E. umbellata is a potential source of antioxidants with therapeutic importance.

Inhibitory Effect of Phragmanthera Incana (Schum.) Harvested from Cocoa (Theobroma Cacao) and Kolanut (Cola Nitida) Trees on Fe2+ induced Lipid Oxidative Stress in Some Rat Tissues - In Vitro

Evidence in both experimental and clinical studies has shown the participation of oxidative stress in the development and progression of diabetes mellitus. This study therefore, sought to investigate the inhibitory effect of methanolic extract of Phragmanthera incana leaves, a mistletoe species harvested from Cocoa (Theobroma cacao) and Kolanut (Cola nitida) on FeSO4 induced lipid peroxidation in rat pancreas, liver, kidney, heart and brain in vitro. The methanolic extract was prepared with 90% methanol (v/v); subsequently, the antioxidant properties and inhibitory effect of the extract on Fe2+ induced lipid peroxidation in some rat tissues were determined in vitro. Incubation of the different rat tissues homogenate in the presence of Fe caused a significant increase in the malondialdehyde (MDA) contents of the tissues. However, the methanolic extracts of Phragmanthera incana leaves harvested from both Cocoa and Kolanut trees caused a significant decrease in the MDA contents of all the tissues tested in a dose-dependent manner. However, the extract of Phragmanthera incana leaves harvested from kolanut trees had a better inhibitory effect on Fe2+- induced lipid peroxidation in the rat tissues homogenates than that of Phragmanthera incana leaves harvested from cocoa trees. This higher inhibitory effect could be attributed to its significantly higher antioxidant properties as typified by their phenolic content, DPPH radical scavenging ability and reducing power. Therefore, oxidative stress associated with diabetes and its other complications could be potentially managed/prevented by harnessing Phragmanthera incana leaves as cheap nutraceuticals. However, Phragmanthera incana leaves harvested from kolanut trees exhibited better antioxidant properties.

Beneficial antioxidant properties of betaine against oxidative stress mediated by levodopa/benserazide in the brain of rats.

The present study was designed to evaluate antioxidant effects of betaine in the brain following administration of levodopa and benserazide, which are routinely used in the treatment of Parkinson's disease. Sprague-Dawley male rats were divided into levodopa (LD), Betaine (Bet.), levodopa plus betaine (LD/Bet.), levodopa plus benserazide (LD/Ben.), levodopa plus betaine-benserazide (LD/Bet.-Ben.) and control groups. The experimental groups received LD 300mg/kg, Bet. 1.5% w/w of the total diet, Ben. 75mg/kg and distilled water to controls for 10 consecutive days, orally. The concentration of plasma total homocysteine significantly increased in LD/Ben.-treated rats when compared to the other groups. Brain glutathione peroxidase (GPx) activity and glutathione content both elevated with betaine treatment in LD/Bet. and LD/Bet.-Ben groups. Superoxide dismutase activity was also higher in controls and betaine-treated rats in comparison with LD and LD/Ben. groups. Likewise, catalase activity significantly increased in control and betaine groups when compared to LD- and LD/Ben.-treated rats. In contrast, brain lipid peroxidation significantly increased in response to LD and LD/Ben. Regarding metabolism of LD in peripheral tissues, serumic dopamine concentration significantly increased in LD-treated rats in comparison with LD/Ben. group. The present results show beneficial antioxidant and methyl donor properties of betaine versus oxidative stress and hyperhomocysteinemia induced by levodopa and benserazide in an animal model.

Prenatal malnutrition and lead intake produce increased brain lipid peroxidation levels in newborn rats

Objectives: Prenatal malnutrition (M) and lead intoxication (Pb) have adverse effects on neuronal development; one of the cellular mechanisms involved is a disruption of the pro- and anti-oxidant balance. In the developing brain, the vulnerability of neuronal membrane phospholipids is variable across the different brain areas. This study assesses the susceptibility of different brain regions to damage by quitar tissue oxidative stress and lead quitar concentrations to determine whether the combined effect of prenatal malnutrition (M) and lead (Pb) intoxication is worse than the effect of either of them individually.Methods: M was induced with an isocaloric and hypoproteinic (6% casein) diet 4 weeks before pregnancy. Intoxication was produced with lead acetate in drinking water, from the first gestational day. Both the M and Pb models were continued until the day of birth. Four brain regions (hippocampus, cortex, striatum, and cerebellum) were dissected out to analyze the lipid peroxidation (LP) levels in four groups: normally nourished (C); normally nourished but intoxicated with lead (CPb); malnourished (M); and M intoxicated with lead (MPb).Results: Dam body and brain weights were significantly reduced in the fourth gestational week in the MPb group. Their pups had significantly lower body weights than those in the C and CPb groups. The PbM group exhibited significant increases of lead concentration and LP in all areas evaluated. A potentiation effect of Pb and M on LP was found in the cerebellum.Discussion: This study provides information on how environmental conditions (intoxication and malnutrition) during the intrauterine period could differentially affect the development of neuronal plasticity and, in consequence, alter adult brain functions such as learning and memory.

A high dose of short term exogenous d-galactose administration in young male rats produces symptoms simulating the natural aging process

Aimsd-Galactose (d-gal) induced accelerated senescence has been used to develop an aging model for brain. Previously, long term administration of a wide range of doses has been used for this purpose. In the present study we investigate whether short term administration of a high dose of d-gal in rats induces significant signs and symptoms similar to natural aging. Main methodsYoung rats were injected intraperitoneally with d-gal at a dose of 300mg/ml/kg for one week. Behavioral analysis for depression and anxiety like symptoms were monitored by forced swim test (FST) and light/dark transition (LDT) test. Assessment of memory was done using the Morris water maze (MWM), passive avoidance test (PAT) and elevated plus maze (EPM) test. Biochemical analysis was done for estimation of antioxidant enzymes and acetylcholinesterase. Determination of brain biogenic amines was performed by HPLC–EC. Key findingsShort term administration of d-gal significantly altered behavioral, biochemical and neurochemical responses in rats. d-Gal injected rats exhibited depressogenic and anxiogenic behaviors while memory was also significantly impaired in these rats. Brain lipid peroxidation and superoxide dismutase activity were significantly increased while catalase and glutathione peroxidase decreased. Increased activity of acetylcholinesterase was also exhibited by d-gal injected rats while brain biogenic amines were significantly decreased. Food intake and growth rate were however comparable in both groups. SignificanceTogether the behavioral, biochemical and neurochemical impairments following the high dose of d-gal suggest that symptoms similar to natural aging may be developed in rats in as early as one week.

Lipid peroxidation in brain or spinal cord mitochondria after injury.

Extensive evidence has demonstrated an important role of oxygen radical formation (i.e., oxidative stress) as a mediator of the secondary injury process that occurs following primary mechanical injury to the brain or spinal cord. The predominant form of oxygen radical-induced oxidative damage that occurs in injured nervous tissue is lipid peroxidation (LP). Much of the oxidative stress in injured nerve cells initially begins in mitochondria via the generation of the reactive nitrogen species peroxynitrite (PN) which then can generate multiple highly reactive free radicals including nitrogen dioxide (•NO2), hydroxyl radical (•OH) and carbonate radical (•CO3). Each can readily induce LP within the phospholipid membranes of the mitochondrion leading to respiratory dysfunction, calcium buffering impairment, mitochondrial permeability transition and cell death. Validation of the role of LP in central nervous system secondary injury has been provided by the mitochondrial and neuroprotective effects of multiple antioxidant agents which are briefly reviewed.

Mercury-induced neurotoxicity and neuroprotective effects of berberine.

Mercury-induced neurotoxicity and neuroprotective effects of berberine.