scholarly journals Neurodevelopmental Toxic Effects of Food Additives Used in Energy Drinks on Developing Rats

2020 ◽  
Vol 27 (2) ◽  
pp. 183-193
Author(s):  
Revathi Boyina ◽  
Sujatha Dodoala

Background: Food additives are widely used in energy drinks and when taken above acceptable daily intake leads to various neurodevelopmental toxic effects. The present study aimed to evaluate the neurodevelopmental toxic effects in rat pups after pre and postnatal administration of selected food additives in pregnant animals. Methods: Pregnant rats aged 160-180 days were divided into six groups with four animals per group. Group 1 treated with vehicle, group 2 standard (caffeine 25 mg/kg p.o.), groups 3-6 were treated with glucuronolactone (5 mg/kg p.o.), taurine (8 mg/kg p.o.), gluconolactone (84 mg/kg p.o.), and combination of food additives respectively till postnatal day (PND) 15. After PND 21, pups were evaluated for neurobehavioural parameters using the behavioral alteration test, Morris water maze test, locomotor activity test, Y-maze test, hot plate latency and neurobehavioural scoring. Neurotransmitters were estimated in brain tissue extract on PND 30, 45 and 60 and histological observations were examined in the brain cortex region. Results: Food additive treated groups showed an increase in behavioral activity, escape latency, immobility, percentage of alterations, hot plate latency and neurobehavioural scoring at selected dose and combination compared to control (p<0.001). The decrease in neurotransmitter levels in the brain and marked degeneration of neurons in the cortex were observed significantly in group6 pups. Conclusion: The present results corroborate that food additives in combination induced neurodevelopmental toxic effects further mechanistic studies are suggested to understand the synergistic effect.

2018 ◽  
Vol 76 (1) ◽  
pp. 32-40 ◽  
Author(s):  
Yousef Baghcheghi ◽  
Mahmoud Hosseini ◽  
Farimah Beheshti ◽  
Hossein Salmani ◽  
Akbar Anaeigoudari

ABSTRACT In this study, the effect of thymoquinone (TQ) on propylthiouracil (PTU)-induced memory impairment was investigated in juvenile rats. The rats were grouped into control, Hypo, Hypo-TQ5 and Hypo-TQ10. Propylthiouracil increased latency time in the Morris water maze test and decreased delay in entering the dark compartment in the passive avoidance test. Both 5 mg/kg and 10 mg/kg doses of TQ decreased latency time in the Morris water maze test and increased delay in entering the dark compartment in a passive avoidance test. The PTU also increased malondialdehyde and nitric oxide metabolites in the brain while reduced the thiol content and superoxide dismutase and catalase activities and serum T4 level. Both doses of TQ decreased malondialdehyde and nitric oxide metabolites in the brain while enhanced the thiol content and superoxide dismutase and catalase activities and serum T4 level. The results of the present study showed that TQ protected against PTU-induced memory impairments in rats.


2011 ◽  
Vol 39 (03) ◽  
pp. 551-563 ◽  
Author(s):  
Chuan-Sung Chiu ◽  
Yung-Jia Chiu ◽  
Lung-Yuan Wu ◽  
Tsung-Chun Lu ◽  
Tai-Hung Huang ◽  
...  

This study attempted to access the neuroprotective effect of diosgenin on the senescent mice induced by d-galactose (D-gal). The mice in the experiments were orally administered with diosgenin (1, 5, 25 and 125 mg/kg), for four weeks from the sixth week. The learning and memory abilities of the mice in Morris water maze test and the mechanism involved in the neuroprotective effect of diosgenin on the mice brain tissue were investigated. Diosgenin (5, 25 and 125 mg/kg, p.o.) showed significantly improved learning and memory abilities in Morris water maze test compared to D-gal treated mice (200 mg/kg, ten weeks). Diosgenin also increased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and decreased the malondialdehyde (MDA) level in the brain of D-gal treated mice. These results indicated that diosgenin has the potential to be a useful treatment for cognitive impairment. In addition, the memory enhancing effect of diosgenin may be partly mediated via enhancing endogenous antioxidant enzymatic activities.


2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Jiling Huang ◽  
Zhigang Gong ◽  
Yingnan Kong ◽  
Yanwen Huang ◽  
Hui Wang ◽  
...  

Objective. To investigate the effect of electroacupuncture (EA) on cognitive dysfunction in rats with hepatic encephalopathy and its underlying mechanism. Methods. Fifty Wistar rats were randomly divided into a normal group (n = 10) and model group (n = 40). Rat models of hepatic encephalopathy were established by administration of carbon tetrachloride and thioacetamide for a total of 12 weeks. At the 9th week after modeling, rats with cognitive impairment in the model group were identified by conducting the Morris water maze test, which were then randomly divided into a control group (CCl4) and treatment groups including EA group (CCl4 + EA), lactulose group (CCl4 + Lac), and EA plus lactulose group (CCl4 + CM), with 9 rats in each group. At the end of the 9th week, rats in CCl4 + Lac and CCl4 + CM groups had lactulose gavage at a dose of 10 mL/kg body weight, while normal control and CCl4 groups had gavage with the same volume of normal saline once a day for 21 days until the end of the experiment. Rats in CCl4 + EA and CCl4 + CM groups underwent acupuncture at Baihui (GV[DU]20), Shenting (GV[DU]24), and Zusanli (ST36) acupoints, among which EA at Baihui and Shenting acupoints were given once daily for 30 min lasting for 21 consecutive days. The effect of the treatment was measured by the Morris water maze test for learning and memory ability and magnetic resonance spectroscopy (MRS) for neuronal metabolism in the hippocampus of rats with hepatic encephalopathy. Pathological change in the rat hippocampus was observed by HE staining, while serum ammonia and liver function markers were detected. Western blot and real-time fluorescent quantitative PCR were used to detect the expressions of specific genes and proteins in the brain tissue. Results. Compared with those in the control group, rats undergoing EA had significantly shortened escape latency and increased number of platform crossing. H&E staining confirmed that EA improved brain tissue necrosis and ameliorated nuclear pyknosis in rats with hepatic encephalopathy. Significantly decreased levels of serum ammonia, alanine aminotransferase (ALT), aspartate transaminase (AST), total bilirubin (TBil), and total bile acid (TBA) were observed in rats undergoing EA, as well as improved levels of total protein (TP) and albumin (ALB). In addition, EA inhibited the brain expressions of TNF-α, IL-1β, IL-6, iNOS, TLR4, MyD88, NF-κB, p38MAPK, phosphorylated (p)-p38MAPK, STAT3, and p-STAT3 genes, as well as protein expressions of TNF-α, IL-6, TLR4, MyD88, NF-κB, p38MAPK, p-p38MAPK, STAT3, and p-STAT3. MRS showed increased Glx/Cr and decreased NAA/Cr, Cho/Cr and mI/Cr in the control group, and EA significantly reversed such changes in Glx/Cr and mI/Cr values. Conclusion. EA ameliorated the production of excessive proinflammatory cytokines in the hippocampus of rats with cognitive dysfunction secondary to hepatic encephalopathy, which also gave rise to subsequent changes such as reduced blood ammonia level, brain-protective activated astrocytes, and lower degree of brain tissue injury. The p38MAPK/STAT3 and TLR4/MyD88/NF-κB signaling pathways may be involved. EA can also improve the metabolism of NAA and Cho in the rat hippocampus and thereby improve learning and memory abilities.


2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Xianying Fang ◽  
Yan Jiang ◽  
Hui Ji ◽  
Linguo Zhao ◽  
Wei Xiao ◽  
...  

This study reports the combination of Ginkgo flavonoid (GF) andCoriolus versicolorpolysaccharide (CVP) in the prevention and treatment of a mouse model of Alzheimer’s disease (AD). GF is a traditional health product, and CVP is the main active ingredient of the medicinal fungusCoriolus versicolor. The Morris water maze test, the Y maze, and the step-through test showed that the combinational use of CVP and GF synergistically improved memory in a mouse model of AD. Based on H&E staining analysis, the combination of CVP and GF decreased the severity of the pathological findings in the brain. Given that the expression of IL-1β, IL-6, and TNF-αwas downregulated, the inflammation response in AD mice was considered to be inhibited. The downregulation of GFAP further demonstrated that inflammation was reduced in the brain of AD mice following treatment. Moreover, the expression levels of superoxide dismutase (SOD) and catalase (CAT) were elevated in the brains of treated mice, indicating that oxidation levels were reduced upon the combination treatment. Our results provide new insights into the efficient utilization of traditional medicine for preventing dementia.


Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Xiaomei Xie ◽  
Kangping Song ◽  
Li'an Huang

Objective: Chronic cerebral hypoperfusion (CCH) is a common consequence of various cerebral vascular disorders, hemodynamics and blood composition changes, which can lead to neurodegenerative injury and cognitive dysfunction. Therefore, it is important to take measures to prevent or reverse its development. Methods: Eighty Sprague-Dawley rats were randomly divided into five groups: Sham group, Vehicle groups (2-week group and 4-week group), Rosuvastatin-treated groups (2-week group and 4-week group). Both vehicle and treated group rats were treated with bilateral common carotid artery occlusion (BCCAO). Then rats in the treated group were intravenously injection with rosuvastatin (0.2 mg/kg/day) daily for 14 days beginning 24 hours after BCCAO. The vehicle groups were given the same amount of saline. The MRI ASL technique was used to scan cerebral blood flow (CBF) at pre-occlusion, BCCAO, 1, 2, 3, and 4 weeks after operation. Morris water maze test detected spatial memory abilities of the treated and vehicle rats after BCCAO. Immunofluorescence staining was used to detect the expression of CD34, GFAP, NeuN and Caspase-3 positive cells in hippocampus. Results: CBF decreased significantly after BCCAO in both rosuvastatin-treated and vehicle groups and then increased gradually. The CBF of the treated group was basically recovered to baseline levels at 1 or 2 weeks after BCCAO. But it took the vehicle group 4 weeks to restore to baseline. The vertebral artery (VA) diameter of the treated group was greater than that of the vehicle group (p<0.05), and the recovery of CBF and the dilation of VA were more evident during the administration period. Similarly, the escape latency of the treated group rats was also less than the vehicle group in Morris Water Maze test. In addition, the number of CD34 + and NeuN + cells in the hippocampus of the treated group was more than that in the vehicle group (p<0.01), while the number of GFAP + and Caspase-3 + cells was less than in the vehicle group (p<0.01). Conclusion: Rosuvastatin can accelerate the recovery of cerebral blood flow in CCH rats, which may be related to the dilation of VAs and angiogenesis; and its effects on reducing astrocyte activation and neuroprotection may help to ameliorate cognitive dysfunction in CCH rats.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5067-5067
Author(s):  
Qin Yu ◽  
Deju Lin ◽  
Liping Zhou ◽  
Biao Wang ◽  
Lizhen Liu ◽  
...  

Abstract Introduction: Preclinical researches on the use of mesenchymal stem cells (MSCs) transplantation to treat hypoxic-ischemic (HI) brain damage have received some encouraging results. However, the insufficient migration of active cells to damaged tissues has limited their potential therapeutic effects. There is a good evidence that hypoxia inducible factor-1 alpha (HIF-1α) promotes the viability and migration of cells. This study was designed to investigate whether overexpression of HIF-1α in MSCs could be effective to enhance the therapeutic efficiency. Methods: MSCs were obtained from rat femoral and tibial bone marrow, and cells with HIF-1α overexpression were gained by recombinant lentiviral vector. The proliferation and migration of MSCs were assessed by 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and transwell culture system. Additionally, the therapeutic efficiency of MSCs after transplantion on HI brain damage in rats were investigated by Morris water maze test and histological examination to analyse the cognitive and pathological changes, and the recruitment in the hippocampus was also observed microscopically. Results: (1) As evidenced by phase contrast and fluorescence microscopy, more than 90% of the cells were GFP-positive when infected with the HIF-1α or GFP lentiviral, and the protein expression of HIF-1α in HIF-1α transduced MSCs was approximately 2-fold that in normal MSCs and GFP transduced MSCs (P<0.01). The results of MTT assay showed that overexpression of HIF-1α promoted the viability and proliferation of MSCs (P<0.01). (2) Meantime, we found MSCs were enhanced the migration both in vitro and in vivo experiments. According to transwell assay, the number of cells migrating to the lower compartment in HIF-1α overexpression group was more than other two groups (P<0.01). In vivo experiments in HI-induced rats, the number of MSCs in the hippocampus increased gradually in a time-dependent manner from day 7 to day 21 after transplantation. And a remarkably increased in the recruitment of HIF-1α transduced MSCs was observed in the hippocampus at every time point compared with GFP transduced MSCs (P<0.01). (3) HIF-1α overexpression also elevated the therapeutic efficiency of MSCs on behavioral and histological aspect in HI-induced brain damaged rats. Morris water maze test suggested that the rats suffered from cognitive dysfunction due to HI treatment. There were a significantly increased of time in the target quadrant in both MSCs transplanted groups compared with HI-vehicle group, but a more increase in the amount of time have been found in HIF-1α overexpressed MSCs group (P<0.01). In contrast with sham group, the pathological changes of the hippocampus in the HI-vehicle group revealed serious injury, and the cells were disordered and cavitation was visible by hematoxylin and eosin staining, but the damages were partly mitigated in HIF-1α overexpressed MSCs transplanted group as compared to other groups. Conclusion: Taken together, these data indicated that overexpression of HIF-1α could improve the therapeutic efficiency of MSCs, and transplantation of MSCs with HIF-1α overexpression may represent an attractive therapeutic option to treat HI brain damage in the future. Footnotes: This work was financially supported by National Natural Science Foundation of China (Gant No. 81270566, Gant No. 81500114). Disclosures No relevant conflicts of interest to declare.


2020 ◽  
Vol 23 (5) ◽  
pp. 402-410 ◽  
Author(s):  
Lin-Zi Li ◽  
Shan-Shan Lei ◽  
Bo Li ◽  
Fu-Chen Zhou ◽  
Ye-Hui Chen ◽  
...  

Aim and Objective: The Dendrobium officinalis flower (DOF) is popular in China due to common belief in its anti-aging properties and positive effects on “nourish yin”. However, there have been relatively few confirmatory pharmacological experiments conducted to date. The aim of this work was to evaluate whether DOF has beneficial effects on learning and memory in senescent rats, and, if so, to determine its potential mechanism of effect. Materials and Methods: SD rats were administrated orally DOF at a dose of 1.38, or 0.46 g/kg once a day for 8 weeks. Two other groups included a healthy untreated control group and a senescent control group. During the 7th week, a Morris water maze test was performed to assess learning and memory. At the end of the experiment, serum and brain samples were collected to measure concentrations of antioxidant enzymes, including malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GSH-Px) in serum, and the neurotransmitters, including γ-aminobutyric acid (γ-GABA), Glutamic (Glu), and monoamine oxidase B (MAO-B) in the brain. Histopathology of the hippocampus was assessed using hematoxylin-eosin (H&E) staining. Results: The results suggested that treatment with DOF improved learning as measured by escape latency, total distance, and target quadrant time, and also increased levels of γ-GABA in the brain. In addition, DOF decreased the levels of MDA, Glu, and MAO-B, and improved SOD and GSHPx. Histopathological analysis showed that DOF also significantly reduced structural lesions and neurodegeneration in the hippocampus relative to untreated senescent rats. Conclusion: DOF alleviated brain aging and improved the spatial learning abilities in senescent rats, potentially by attenuating oxidative stress and thus reducing hippocampal damage and balancing the release of neurotransmitters.


2019 ◽  
Vol 16 (8) ◽  
pp. 710-722 ◽  
Author(s):  
Xiao-Ying Sun ◽  
Quan-Xiu Dong ◽  
Jie Zhu ◽  
Xun Sun ◽  
Li-Fan Zhang ◽  
...  

Background: Alzheimer’s Disease (AD) is characterized by the presence of extracellular amyloid-β (Aβ) plaques and intraneuronal neurofibrillary tangles assembled by the microtubuleassociated protein tau. Increasing evidence demonstrated that tau pathology played an important role in AD progression. Resveratrol (RSV) has previously proved to exert neuroprotective effect against AD by inhibiting Aβ generation and Aβ-induced neurocytotoxicity, while its effect on tau pathology is still unknown. Method: The effect of RSV on tau aggregation was measured by Thioflavin T fluorescence and Transmission electron microscope imaging. The effect of RSV on tau oligomer-induced cytotoxicity was assessed by MTT assay and the uptake of extracellular tau by N2a cells was determined by immunocytochemistry. 6-month-old male PS19 mice were treated with RSV or vehicle by oral administration (gavage) once a day for 5 weeks. The cognitive performance was determined using Morris water maze test, object recognition test and Y-maze test. The levels of phosphorylated-tau, gliosis, proinflammatory cytokines such as TNF-α and IL-1β, and synaptic proteins including synaptophysin and PSD95 in the brains of the mice were evaluated by immunoblotting, immunostaining and ELISA, respectively. Results: RSV significantly inhibited tau aggregation and tau oligomer-induced cytotoxicity, and blocked the uptake of extracellular tau oligomers by N2a cells. When applied to PS19 mice, RSV treatment effectively rescued cognitive deficits, reducing the levels of phosphorylated tau, neuroinflammation and synapse loss in the brains of mice. Conclusion: These findings suggest that RSV has promising therapeutic potential for AD and other tauopathies.


Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3442
Author(s):  
Yaowared Chulikhit ◽  
Wichitsak Sukhano ◽  
Supawadee Daodee ◽  
Waraporn Putalun ◽  
Rakvajee Wongpradit ◽  
...  

The effects of the phytoestrogen-enriched plant Pueraria mirifica (PM) extract on ovari-ectomy (OVX)-induced cognitive impairment and hippocampal oxidative stress in mice were investigated. Daily treatment with PM and 17β-estradiol (E2) significantly elevated cognitive behavior as evaluated by using the Y maze test, the novel object recognition test (NORT), and the Morris water maze test (MWM), attenuated atrophic changes in the uterus and decreased serum 17β-estradiol levels. The treatments significantly ameliorated ovariectomy-induced oxidative stress in the hippocampus and serum by a decrease in malondialdehyde (MDA), an enhancement of superoxide dismutase, and catalase activity, including significantly down-regulated expression of IL-1β, IL-6 and TNF-α proinflammatory cytokines, while up-regulating expression of PI3K. The present results suggest that PM extract suppresses oxidative brain damage and dysfunctions in the hippocampal antioxidant system, including the neuroinflammatory system in OVX animals, thereby preventing OVX-induced cognitive impairment. The present results indicate that PM exerts beneficial effects on cognitive deficits for which menopause/ovariectomy have been implicated as risk factors.


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