scholarly journals Neuroprotective Effect of α-Mangostin in Ameliorating Propionic Acid-Induced Experimental Model of Autism in Wistar Rats

2021 ◽  
Vol 11 (3) ◽  
pp. 288 ◽  
Author(s):  
Aarti Tiwari ◽  
Rishabh Khera ◽  
Saloni Rahi ◽  
Sidharth Mehan ◽  
Hafiz Antar Makeen ◽  
...  

Several studies have documented the role of hyper-activation of extracellular signal-regulated kinases (ERK) in Autism pathogenesis. Alpha-mangostin (AMG) is a phytoconstituents with anti-oxidants, anti-inflammatory, and ERK inhibition properties in many diseases. Our research aims to investigate the neuroprotective effect of AMG in the rat model of intracerebroventricular-propionic acid (ICV-PPA) induced autism with a confirmation of its effect on the ERK signaling. Autism was induced in Wistar rats (total 36 rats; 18 male/18 female) by multiple doses of PPA through ICV injection for 11 days. Actophotometer and beam walking tasks were used to evaluate animals’ motor abilities, and the Morris water maze task was utilized to confirm the cognition and memory in animals. Long term administration of AMG100 mg/kg and AMG200 mg/kg continued from day 12 to day 44 of the experiment. Before that, animals were sacrificed, brains isolated, morphological, gross pathological studies were performed, and neurochemical analysis was performed in the brain homogenates. Cellular and molecular markers, including ERK, myelin basic protein, apoptotic markers including caspase-3, Bax, Bcl-2, neuroinflammatory markers, neurotransmitters, and oxidative stress markers, have been tested throughout the brain. Thus, AMG reduces the overactivation of the ERK signaling and also restored autism-like behavioral and neurochemical alterations.

2021 ◽  
Vol 15 (4) ◽  
pp. 249-256
Author(s):  
Taiwo Adekemi Abayomi ◽  
◽  
Olorunfemi Samuel Tokunbo ◽  
Moyinoluwa Ajayi ◽  
Olawale Ayobami Abayomi ◽  
...  

Background: Although ethanol exerts its neurotoxic effect on the brain through inflammatory and oxidative processes, the effect of Riboceine on the brain following ethanol neurotoxicity is yet to be elucidated. Therefore, this study was designed to evaluate the effects of riboceine on the cellular, behavioral, and molecular impairments induced by ethanol toxicity in rats. Methods: A total of 24 male Wistar rats weighing between 160-170 grams were used for the study, and were divided into four groups of six rats each. After completion of the administration of ethanol and riboceine, and testing for motor impairment, the rats were sacrificed. The cerebellum was excised and processed for oxidative stress analyses, based on oxidative stress markers and histological examinations. The immunohistochemical expression of astrocytes in the cerebellum was examined, using Glial Fibrillary Acidic Protein (GFAP) stain. Results: This study demonstrated that ethanol-induced neurotoxicity in the cerebellum, characterized by increased oxidative stress profile, astrocyte activation, and neuronal death in the cerebellum, especially the Purkinje layer. Necrosis, significant decrease in Superoxide Dismutase (SOD), Catalase (CAT) and Gluathione (GSH) activities (P<0.05) as well as astrogliosis was associated with ethanol treatment. However, riboceine was observed to significantly increase the cerebellar SOD, CAT and GSH activities with significantly reduced Malondialdehyde (MDA) levels (P<0.05). It also attenuated the histomorphological alteration of the cerebellum and reduced the cerebellar astrocytes activation following ethanol-induced neurotoxicity, thus leading to the attenuation of motor impairment. Conclusion: Riboceine attenuated motor impairment caused by chronic ethanol-induced neurotoxicity, suggestive of its anti-oxidative and anti-inflammatory properties.


2020 ◽  
Vol 2020 ◽  
pp. 1-7 ◽  
Author(s):  
Samuel Bolaji Mesole ◽  
Okpanachi Omachonu Alfred ◽  
Uthman Ademola Yusuf ◽  
Lwiindi Lukubi ◽  
Dailesi Ndhlovu

Aluminium is known to accelerate oxidative stress, amyloid beta (Aβ) deposition, and plaque formation in the brain of rats. Objective. The present study is aimed at studying the neuroprotective effects of eugenol following aluminium-induced neurotoxicity on caspase-3, apoptotic proteins (Bcl-2 and Bax), and oxidative stress markers in Wistar rats such as superoxide dismutase (SOD), glutathione peroxidase (GPx), nitric oxide (NO), and assay oxidative stress to mitochondrial DNA (mtDNA) by measuring the levels of 8-hydroxy-2-deoxyguanosine (8-OHdG). Materials and methods. Twenty (20) adult Wistar rats were randomly divided into four (4) groups with five animals in each group. Route of administration was oral throughout the duration of this study and this study lasted for 21 days. Rats were sacrificed 24 hours after administration of the last dose (i.e., day 22) with 0.8 mg/kg ketamine as an anaesthetic agent. Results. Exposure to AlCl3 resulted in a significant (p<0.01) elevation in the levels of nitric oxide and 8-hydroxy-2-deoxyguanosine (8-OHdG), enhanced the activity of caspase-3, increased the level of proapoptotic protein Bax and reduced the levels of antiapoptotic protein Bcl-2, and significantly (p<0.01) reduced the levels of SOD and GPx. However, treatment with eugenol resulted in a significant reduction (p<0.01) in the levels of nitric oxide (NO) and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels, inhibited the activity of caspase-3, increased levels of Bcl-2 and significantly (p<0.05) reduced levels of Bax protein, respectively, and also significantly (p<0.05) increased the levels of SOD and GPx. Our results would hereby suggest that eugenol would provide a therapeutic value against aluminium-induced oxidative stress as related to antioxidant and antiapoptotic activities.


2016 ◽  
Vol 33 (5) ◽  
pp. 454-468 ◽  
Author(s):  
Kalist Shagirtha ◽  
Nazima Bashir ◽  
Selvaraj MiltonPrabu

The present study was designed to investigate the neuroprotective effect of hesperetin (Hp) against cadmium (Cd)-induced neurotoxicity in rats. Cadmium (3 mg/kg body weight (b.w.), subcutaneous) administration for 3 weeks demonstrated neurotoxicity in rats by the decreased activity of acetylcholinesterase in the brain. The oxidative stress markers (thiobarbituric acid reactive substances and protein carbonyls) were significantly increased with decreased enzymatic (superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase) and non-enzymatic antioxidants (reduced glutathione, total sulphydryl groups and vitamin C). The proteolytic and membrane-bound enzymes (Na+ K+-ATPase, Mg2+-ATPase and Ca2+-ATPase) were also decreased with increased apoptotic markers (Bcl2 Associated X Protein (Bax), cytochrome C, caspase 3 and 9) and decreased anti-apoptotic marker (B-cell lymphoma 2 (Bcl2)) in the brain of Cd-treated rats. Moreover, Cd administration significantly decreased the mitochondrial electron transport chain complexes (I, II, III and IV) in the brain of rats. Preadministration of Hp (40 mg/kg b.w., oral) significantly attenuated the Cd-induced oxidative stress and mitochondrial dysfunction, restored the antioxidant and membrane-bound enzyme activities and decreased apoptosis in the brain of rats.


Author(s):  
D.N. Collins ◽  
J.N. Turner ◽  
K.O. Brosch ◽  
R.F. Seegal

Polychlorinated biphenyls (PCBs) are a ubiquitous class of environmental pollutants with toxic and hepatocellular effects, including accumulation of fat, proliferated smooth endoplasmic recticulum (SER), and concentric membrane arrays (CMAs) (1-3). The CMAs appear to be a membrane storage and degeneration organelle composed of a large number of concentric membrane layers usually surrounding one or more lipid droplets often with internalized membrane fragments (3). The present study documents liver alteration after a short term single dose exposure to PCBs with high chlorine content, and correlates them with reported animal weights and central nervous system (CNS) measures. In the brain PCB congeners were concentrated in particular regions (4) while catecholamine concentrations were decreased (4-6). Urinary levels of homovanillic acid a dopamine metabolite were evaluated (7).Wistar rats were gavaged with corn oil (6 controls), or with a 1:1 mixture of Aroclor 1254 and 1260 in corn oil at 500 or 1000 mg total PCB/kg (6 at each level).


Molecules ◽  
2021 ◽  
Vol 26 (10) ◽  
pp. 2954
Author(s):  
Justyna Gorzkiewicz ◽  
Grzegorz Bartosz ◽  
Izabela Sadowska-Bartosz

Phytoestrogens are naturally occurring non-steroidal phenolic plant compounds. Their structure is similar to 17-β-estradiol, the main female sex hormone. This review offers a concise summary of the current literature on several potential health benefits of phytoestrogens, mainly their neuroprotective effect. Phytoestrogens lower the risk of menopausal symptoms and osteoporosis, as well as cardiovascular disease. They also reduce the risk of brain disease. The effects of phytoestrogens and their derivatives on cancer are mainly due to the inhibition of estrogen synthesis and metabolism, leading to antiangiogenic, antimetastatic, and epigenetic effects. The brain controls the secretion of estrogen (hypothalamus-pituitary-gonads axis). However, it has not been unequivocally established whether estrogen therapy has a neuroprotective effect on brain function. The neuroprotective effects of phytoestrogens seem to be related to both their antioxidant properties and interaction with the estrogen receptor. The possible effects of phytoestrogens on the thyroid cause some concern; nevertheless, generally, no serious side effects have been reported, and these compounds can be recommended as health-promoting food components or supplements.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ruiqing Zhu ◽  
Hui Wang ◽  
Xinping Xu ◽  
Li Zhao ◽  
Jing Zhang ◽  
...  

AbstractPrevious studies have shown that single-frequency microwave radiation can lead to cognitive decline in rats. However, few studies have focused on the combined effects of irradiation with different frequencies of microwaves. Our research aimed to investigate the effects of 1.5 GHz and 4.3 GHz microwave radiation, singly and in combination, on cognitive function and hippocampal tissue structure in rats. A total of 140 male Wistar rats were randomly divided into 4 groups: the S group (sham radiation group), L10 group (10 mW/cm2 1.5 GHz group), C10 group (10 mW/cm2 4.3 GHz band group) and LC10 group (10 mW/cm2 1.5 and 4.3 GHz multi-frequency radiation group). For 1–28 days after microwave radiation, we analyzed the average escape latency for the Morris water maze task, electroencephalograms, change in hippocampal tissue structure and ultrastructure, content of the Nissl body in the hippocampus, and activities of lactate dehydrogenase and succinate dehydrogenase. Compared to the S group, all exposure groups showed varying degrees of learning and memory decline and hippocampal structural damage. The results showed that 1.5 GHz and 4.3 GHz microwave radiation was able to induce cognitive impairment and hippocampal tissue damage in rats and combined radiation with both frequencies caused more serious injuries, but none of these damaging effects varied with microwave frequency.


2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Jintanaporn Wattanathorn ◽  
Jinatta Jittiwat ◽  
Terdthai Tongun ◽  
Supaporn Muchimapura ◽  
Kornkanok Ingkaninan

Cerebral ischemia is known to produce brain damage and related behavioral deficits including memory. Recently, accumulating lines of evidence showed that dietary enrichment with nutritional antioxidants could reduce brain damage and improve cognitive function. In this study, possible protective effect ofZingiber officinale, a medicinal plant reputed for neuroprotective effect against oxidative stress-related brain damage, on brain damage and memory deficit induced by focal cerebral ischemia was elucidated. Male adult Wistar rats were administrated an alcoholic extract of ginger rhizome orally 14 days before and 21 days after the permanent occlusion of right middle cerebral artery (MCAO). Cognitive function assessment was performed at 7, 14, and 21 days after MCAO using the Morris water maze test. The brain infarct volume and density of neurons in hippocampus were also determined. Furthermore, the level of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in cerebral cortex, striatum, and hippocampus was also quantified at the end of experiment. The results showed that cognitive function and neurons density in hippocampus of rats receiving ginger rhizome extract were improved while the brain infarct volume was decreased. The cognitive enhancing effect and neuroprotective effect occurred partly via the antioxidant activity of the extract. In conclusion, our study demonstrated the beneficial effect of ginger rhizome to protect against focal cerebral ischemia.


2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Felipe Ornell ◽  
Samira S. Valvassori ◽  
Amanda V. Steckert ◽  
Pedro F. Deroza ◽  
Wilson R. Resende ◽  
...  

The effects of modafinil (MD) on behavioral and oxidative damage to protein and lipid in the brain of rats were evaluated. Wistar rats were given a single administration by gavage of water or MD (75, 150, or 300 mg/kg). Behavioral parameters were evaluated in open-field apparatus 1, 2, and 3 h after drug administration. Thiobarbituric acid reactive substances (TBARS) and protein carbonyl formation were measured in the brain. MD increased locomotor activity at the highest dose 1 and 3 h after administration. MD administration at the dose of 300 mg/kg increased visits to the center of open-field 1 h after administration; however, 3 h after administration, all administered doses of MD increased visits to the open-field center. MD 300 mg/kg increased lipid damage in the amygdala, hippocampus, and striatum. Besides, MD increased protein damage in the prefrontal cortex, amygdala, and hippocampus; however, this effect varies depending on the dose administered. In contrast, the administration of MD 75 and 300 mg/kg decreased the protein damage in the striatum. This study demonstrated that the MD administration induces behavioral changes, which was depending on the dose used. In addition, the effects of MD on oxidative damage parameters seemed to be in specific brain region and doses.


2021 ◽  
pp. 13-19
Author(s):  
Amita Singh ◽  
Raj Kumar ◽  
S. K. Kannaujia ◽  
Manikrishna Manikrishna ◽  
N. P. Singh

Abhrak bhasma (AB) is a type of bhasma prepared from repeated incineration of mineral mica with decoctions of about 72 herbs. The particle size of Abhrak bhasm has been shown to be in the range of 29-88 nanometers and Fe, Ca, Si, Mg and K are found to be as major constituent. Many drugs developed to treat Central Nervous System (CNS) disorders are unable to reach the brain parenchyma in therapeutically relevant concentrations. The blood brain barrier protects brain parenchyma from the uctuation of plasma composition, from pathogenic agents and maintains homeostasis of the brain parenchyma by restricting non-specic ux of ions, peptides, proteins and even cells into and out the brain. Immunohistochemistry is being widely employed as a tool for biological studies. This study is conducted to examine the change in the continuity of Blood brain barrier by using immunohistochemistry, once Abhrak bhasm drug is given in experimental animal and also to examine the histology of organs. In this study a total of 30 adult albino Wistar rats of approximately 4 months age (approx. 150-200 gms) of either sex selected randomly to see the effect of Abhrak bhasm, an ayurvedic drug on Wistar rats. The rats were weighed, marked and divided into 5 groups each consisting of six animals. In normal control group (Group E), no drug was administered and in rest of the four treated groups (Group-A,B,C,D), Abhrak bhasm @ 36 mg/kg B.wt. was administered orally once in each rat. Brain, liver, kidneys,spleen and blood samples were collected in 10% formalin solution after euthanizing the rats at 0.5,2,6 & 12 hours of Abhrak bhasma drug intervention. The alterations in any of the biochemical parameters are within the tolerable limits of liver and kidney since the dose of abhrak bhasm did not affect liver and kidneys. In the present study, the increase in ALP level may be the result of alterations in metabolisms that occurred without any signicant alteration in histology of liver. After applying the immunohistochemistry with the research markers GFAP, CD 34, S 100, GLUT-1 and RECA-1 on the rats in groups A,B,C and D, there was no change in the intensity of immunohistochemistry, with respect to control. While on applying the Occludin, the intensity of immunohistochemistry was reduced in all the treatment groups as compared to the control group. On the basis of ndings of present study it can be concluded that the therapeutic dose of Abhrak bhasma causes changes at the level of tight junctions present in blood brain barrier in rats which is shown by immunohistochemistry with occludin research marker. There is no toxic effect of drug on different organs of rats as no signicant changes in histology of organs are seen. More studies need to be done to check the permeability of blood brain barrier for Abhrak bhasma drug, like calculating its concentration in brain tissues and other vital organs of rat.


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