Brain Antioxidant Defense System Research Articles

Neurotoxic Effect of Fipronil in Male Wistar Rats: Ameliorative Effect of L-Arginine and L-Carnitine.

Simple SummaryInsecticides are widely used in agricultural and household environments. They induce wide range of deleterious effects. Fipronil is one of the most widely used phenylpyrazoles insecticides. The neurotoxic effect of such insecticide was tested in the present study with special emphasis on cognitive deficit as well as testing the possible ameliorative impacts of L-arginine and L-carnitine. The study proposed fipronil-induced cognitive deficit as a reflection to oxidative stress and neuro-inflammation. Moreover, L-arginine and L-carnitine exerted ameliorative influence on fipronil induced oxidative stress and neuro-inflammation. Therefore, L-arginine and L-carnitine can be considered as prospective candidates for mitigation of pesticide induced neurotoxicity especially in people with high-risk exposure to pesticide.The ameliorative effect of L-arginine (LA) and L-carnitine (LC) against fipronil (FPN)-induced neurotoxicity was explored. In this case, 36 adult male rats were randomly divided into six groups: group I received distilled water, group II received 500 mg/kg LA, group III received 100 mg/kg LC, group IV received 4.85 mg/kg FPN, group V received 4.85 mg/kg FPN and 500 mg/kg LA and group VI received 4.85 mg/kg FPN and 100 mg/kg LC for 6 weeks. Cognitive performance was assessed using Barnes maze (BM). Serum corticosterone, brain total antioxidant capacity (TAC), malondialdehyde (MDA) and dopamine were measured. Histopathology and immunohistochemistry of ionized calcium-binding adaptor (Iba-1), doublecortin (DCX) and serotonin (S-2A) receptors were performed. Fipronil induced noticeable deterioration in spatial learning and memory performance. In addition, FPN significantly (p < 0.05) diminished brain antioxidant defense system and dopamine coincide with elevated serum corticosterone level. Histopathological examination revealed degenerative and necrotic changes. Furthermore, Iba-1 and DCX were significantly expressed in cortex and hippocampus whereas S-2A receptors were significantly lowered in FPN group. However, administration of LA or LC alleviated FPN-induced deteriorations. In conclusion, LA and LC could be prospective candidates for mitigation of FPN-induced neurotoxicity via their antioxidant, anti-inflammatory and neuropotentiating effects.

An in silico investigation on the inhibitory potential of the constituents of Pomegranate juice on antioxidant defense mechanism: Relevance to neurodegenerative diseases

Elevation in the levels of reactive oxygen and nitrogen species (RONS), and downregulation of cellular antixoidants, have ubiquitously been reported from studies in animal models of neurodegenerative diseases, including Parkinson’s disease (PD) and Alzheimer’s disease (AD). Thus, plant-derived compounds are widely being investigated for their beneficial effects in these models. However, while studies have reported antioxidant potentials of several phytochemicals, a large number of studies have demonstrated different phytochemicals to be rather pro-oxidant and exaggerate oxidative stress (OS). One such study aimed to investigate possible ameliorative effect of Pomegranate juice (PJ) in rat model of toxin-induced parkinsonism revealed that PJ exacerbates OS, inflammation and promotes neurodegeneration. Thus, it remains to be investigated whether different constituents and metabolites of PJ are pro-oxidant or anti-oxidant. Using computational modeling, we investigated possible inhibitory potential of different constituents of PJ and their metabolites viz. delphinidin-3-glucoside, dimethylellagic acid-glucuronide, ellagic acid, ellagitannin, gallic acid, gallotannin 23, pelargonidin, punicalagin, urolithin A, urolithin A-glucuronide and urolithin B, on anti-oxidant defense system of the brain. The results indicate that the constituents of PJ have the potential to inhibit five key enzymes of the neuronal antioxidant defense system, viz. catalase, superoxide dismutase, glutathione peroxidase 4, glutathione reductase and glutathione-S-transferase. Thus, it is surmised that the constituents of PJ may contribute to OS and neurodegeneration by way of affecting antioxidant defense mechanism. This may particularly be more pronounced in neurodegenerative diseases, since neurons are known to be more vulnerable to OS. Thus, the present findings caution the use of PJ in patients prone to OS, especially those suffering from neurodegenerative diseases, and warrant further experimental studies to unveil the effects of individual components and metabolites of PJ on antioxidant defense system of brain.

Steroid-Enriched Fraction of Achyranthes bidentata Protects Amyloid β Peptide 1-40-Induced Cognitive Dysfunction and Neuroinflammation in Rats.

The roots of Achyranthes bidentata Blume (AB) is commonly used in the treatment of osteoporosis and dementia in traditional Chinese medicine. Pharmacological reports evidenced that AB possessed anti-osteoarthritis effects. However, there is little literature about the anti-dementia activities of AB. The present study was designed to prepare steroid-enriched fraction of AB (ABS) and investigate whether ABS can protect from cognitive dysfunction and neuroinflammation against Aβ 1-40-induced Alzheimer's disease (AD) model in rats. ABS only contained 135.11 ± 4.28mg of ecdysterone per gram. ABS (50mg/kg) reversed the dysfunction of exploratory activity and memory function on plus-maze and Morris water maze caused by Aβ 1-40 in rats. ABS (50mg/kg) also decreased amyloid deposition, neurofibrillary tangle, neural damage, activated astrocyte, and microglial caused by Aβ 1-40. Furthermore, ABS reversed the phenomenon of neural oxidative damage and neuroinflammation, including the higher levels of MDA and cytokines, and the lower activities of antioxidant enzymes and GSH levels caused by Aβ 1-40 in rat cortex and hippocampus. Finally, ABS restored the activation of ERK pathway and decreased NF-κB phosphorylation and translocation altered by Aβ 1-40. ABS alone (50mg/kg) promoted cognitive function, activated brain antioxidant defense system, and decreased brain TNF-α levels in sham group. Therefore, ABS has the cognition-promoting and antidementia potential. Steroids especial ecdysterone are major active components of AB. The action mechanism is due to decreasing oxidative stress and neuroinflammation through modulating ERK pathway, NF-κB phosphorylation, and translocation in Aβ 1-40-induced AD rat model.

Hydroalcoholic extract of Dorema aucheri leaves prevents weakening of the brain antioxidant defense system and inhibits oxidative damage in rat model of ischemic stroke

Hydroalcoholic extract of Dorema aucheri leaves prevents weakening of the brain antioxidant defense system and inhibits oxidative damage in rat model of ischemic stroke

Fullerol potentiates the brain antioxidant defense system and decreases γ-glutamyl transpeptidase (GGT) mRNA during cerebral ischemia/reperfusion injury

AbstractFullerol compounds have potent antioxidant effects on biological systems. Therefore, we examined whether fullerol pretreatment potentiates the brain antioxidant defense system and decreases

Acute and Subchronic Toxicity Study of the Median Septum of Juglans regia in Wistar Rats.

Purpose: Median septum of Juglans regia L. (Juglandaceae) with anti-diabetic effects has been used in Iranian traditional medicine. The present study estimates both oral acute and subchronic toxicities. Methods: In the oral acute toxicity study, female Wistar rats were treated with doses of 10, 100, 1000, 1600, 2900 and 5000 mg/ kg of the Juglans regia septum of methanol extract (JRSME), and were monitored for 14 days. In subchronic study, JRSME was administered by gavage at dose of 1000 mg/kg daily in Wistar rats for 28 days. Antioxidant status and biochemical examinations were fulfilled, and the vital organs were subjected to pathological analyses. Results: The extract did not produce any toxic signs or deaths; the medium lethal dose must be higher than 5000 mg/kg. In subchronic study, No significant morphological and histopathological changes were observed in the studied tissues. There was a significant increase in serum malondialdehyde (MDA) level in treated group compared to control after 4 weeks of JRSME intake. The treatment of rats resulted in a significant reduction of serum urea level (p<0.05), kidney's xanthine dehydrogenase (XDH) activity (p<0.001) and elevation of aldehyde oxidase (AO) activity (p<0.05) in kidney. In the treated group, the mean diameter of glomerulus and proximal urine tube epithelium stature was slightly greater than control group. A significant increase in serum MDA level is subject for further studies. Conclusion: This study showed that the extract has no acute or subacute adverse effects with dose of 1000 mg/kg. The administration of JRSME may improve kidney structure and function and help in treatment of some chronic diseases.

Acute hypertension induces brain injury and blood–brain barrier disruption through reduction of claudins mRNA expression in rat

The present study examined genes transcription of tight junction (TJs) proteins of the blood–brain barrier (BBB) and detrimental effects on the brain tissue after acute hypertension.The experiment was performed in two groups of rats, sham and hypertensive. Rats were made acutely hypertensive by aortic constriction above the renal arteries. After 8 days, arterial pressure was recorded and BBB permeability was evaluated by the Evans blue dye extravasations (EBE) technique. Quantitative RT-PCR was used for assessment of mRNA expression of claudins (claudin-3, 5 & 12). Superoxide dismutase (SOD) and catalase activity, as well as glutathione and malondialdehyde content were determined by biochemical methods. Aortic constriction significantly enhanced arterial pressure and EBE of hypertensive rats by 35% and 76%, respectively. Enzyme activity of SOD and catalase were significantly lower in hypertensive rats. Hypertension significantly decreased the brain glutathione content and increased the brain malondialdehyde level. Also, the mRNA levels of claudins (3, 5 & 12) proteins significantly decreased in response to hypertension. Our findings indicated that acutely elevated arterial pressure provokes brain microvascular permeability by diminution of claudins genes transcription in the endothelial cells of BBB. Our results also showed that short-term hypertension impairs the antioxidant defense system of brain and induces brain injury through oxidative stress.

Influence of Punica granatum L. on region specific responses in rat brain during Alloxan-Induced diabetes

ObjectiveThe present study was carried out to investigate the effects of Punica granatum peel methanolic extract (PGPE) on cerebral cortex (CC) and Hippocampus (HC) brain antioxidant defense system and markers of lipid and protein oxidation in alloxan induced diabetic rats. MethodsOral administration of PGPE (75 and 150 mg of kg body weight) for 45 days resulted in significant reduction in blood glucose levels. ResultsSupplementation of diabetic rats with PGPE showed increased activities of SOD and GPx with concomitant decrease in MDA and PC content. Region-specific changes were more evident in the HC when compared to CC. ConclusionsThe present study indicated that PGPE can ameliorate brain oxidative stress in alloxan induced diabetic rats by up regulating antioxidant defense mechanism by attenuating lipid and protein oxidation. PGPE thus may be used as a potential therapeutic agent in preventing diabetic complications in the brain.

Nootropic activity of acetaminophen against colchicine induced cognitive impairment in rats

Alzheimer’s disease is a devastating neurodegenerative disorder, the most common among the dementing illnesses. Acetaminophen has gaining importance in neurodegenerative diseases by attenuating the dopaminergic neurodegeneration in Caenorhabditis elegans model, decreasing the chemokines and the cytokines and increasing the anti apoptotic protein such as Bcl-2 in neuronal cell culture. The low concentration acetaminophen improved the facilitation to find the hidden platform in Morris Water Maze Test. Also some data suggest that acetaminophen could contribute in neurodegeneration. The present study was aimed to evaluate the effect of acetaminophen against colchicine induced cognitive impairment and oxidative stress in wistar rats. The cognitive learning and memory behaviour was assessed using step through passive avoidance paradigm and acetylcholine esterase activity. The parameters of oxidative stress were assessed by measuring the malondialdehyde, reduced glutathione and catalase levels in the whole brain homogenates. There was a significant memory improvement in the rats received acetaminophen treatment and it has also decreased the acetylcholine esterase enzyme level, confirming its nootropic activity. Acetaminophen neither increases nor decreases the reduced glutathione and catalase in the whole brain homogenates, showing that acetaminophen is devoid of any adverse effect on brain antioxidant defense system.

Carnosine Protects the Brain of Rats and Mongolian Gerbils against Ischemic Injury: After-Stroke-Effect

Carnosine, a specific constituent of excitable tissues of vertebrates, exhibits a significant antioxidant protecting effect on the brain damaged by ischemic-reperfusion injury when it was administered to the animals before ischemic episode. In this study, the therapeutic effect of carnosine was estimated on animals when this drug was administered intraperitoneally (100 mg/kg body weight) after ischemic episode induced by experimental global brain ischemia. Treatment of the animals with carnosine after ischemic episode under long-term (7-14 days) reperfusion demonstrated its pronounced protective effect on neurological symptoms and animal mortality. Carnosine also prevented higher lipid peroxidation of brain membrane structures and increased a resistance of neuronal membranes to the in vitro induced oxidation. Measurements of malonyl dialdehyde (MDA) in brain homogenates showed its increase in the after brain stroke animals and decreased MDA level in the after brain stroke animals treated with carnosine. We concluded that carnosine compensates deficit in antioxidant defense system of brain damaged by ischemic injury. The data presented demonstrate that carnosine is effective in protecting the brain in the post-ischemic period.