scholarly journals Restorative potential of (−)-epicatechin in a rat model of Gulf War illness muscle atrophy and fatigue

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Israel Ramirez-Sanchez ◽  
Viridiana Navarrete-Yañez ◽  
Alejandra Garate-Carrillo ◽  
Modesto Lara-Hernandez ◽  
Judith Espinosa-Raya ◽  
...  
Keyword(s):  
Muscle Atrophy ◽  
Rat Model ◽  
Inflammatory Cytokine ◽  
Gulf War ◽  
Plasma Metabolites ◽  
Control Group ◽  
Loss Of Function ◽  
Gulf War Illness ◽  
Mediators Of Inflammation ◽  
Male Wistar Rats

AbstractWe examined in a rat model of Gulf War illness (GWI), the potential of (−)-epicatechin (Epi) to reverse skeletal muscle (SkM) atrophy and dysfunction, decrease mediators of inflammation and normalize metabolic perturbations. Male Wistar rats (n = 15) were provided orally with pyridostigmine bromide (PB) 1.3 mg/kg/day, permethrin (PM) 0.13 mg/kg/day (skin), DEET 40 mg/kg/day (skin) and were physically restrained for 5 min/day for 3 weeks. A one-week period ensued to fully develop the GWI-like profile followed by 2 weeks of either Epi treatment at 1 mg/kg/day by gavage (n = 8) or water (n = 7) for controls. A normal, control group (n = 15) was given vehicle and not restrained. At 6 weeks, animals were subjected to treadmill and limb strength testing followed by euthanasia. SkM and blood sampling was used for histological, biochemical and plasma pro-inflammatory cytokine and metabolomics assessments. GWI animals developed an intoxication profile characterized SkM atrophy and loss of function accompanied by increases in modulators of muscle atrophy, degradation markers and plasma pro-inflammatory cytokine levels. Treatment of GWI animals with Epi yielded either a significant partial or full normalization of the above stated indicators relative to normal controls. Plasma metabolomics revealed that metabolites linked to inflammation and SkM waste pathways were dysregulated in the GWI group whereas Epi, attenuated such changes. In conclusion, in a rat model of GWI, Epi partially reverses detrimental changes in SkM structure including modulators of atrophy, inflammation and select plasma metabolites yielding improved function.

scholarly journals Restorative Effects of (-)-Epicatechin in a Rat Model of Gulf War Illness Muscle Atrophy and Fatigue

2021 ◽  
Author(s):  
Israel Ramirez-Sanchez ◽  
Viridiana Navarrrete ◽  
Alejandra Garate-Carrillo ◽  
Modesto Lara-Hernandez ◽  
Judith Espinosa-Raya ◽  
...  
Keyword(s):  
Muscle Atrophy ◽  
Rat Model ◽  
Inflammatory Cytokine ◽  
Gulf War ◽  
Plasma Metabolites ◽  
Control Group ◽  
Loss Of Function ◽  
Gulf War Illness ◽  
Mediators Of Inflammation ◽  
Male Wistar Rats

Abstract We examined in a rat model of Gulf War illness (GWI), the potential of (-)-epicatechin (Epi) to reverse skeletal muscle (SkM) atrophy and dysfunction, decrease mediators of inflammation and normalize metabolic perturbations. Male Wistar rats (n = 15) were provided orally with pyridostigmine bromide (PB) 1.3 mg/kg/day, permethrin (PM) 0.13 mg/kg/day (skin), DEET 40 mg/kg/day (skin) and were physically restrained for 5 min/day for 3 weeks. A one-week period ensued to fully develop the GWI-like profile followed by 2 weeks of either Epi treatment at 1 mg/kg/day by gavage (n = 8) or water (n = 7) for controls. A normal, control group (n = 15) was given vehicles and not restrained. At 6 weeks, animals were subjected to treadmill and limb strength testing followed by euthanasia. SkM and blood sampling was used for histological, biochemical and plasma pro-inflammatory cytokine and metabolomics assessments. GWI animals developed an intoxication profile characterized SkM atrophy and loss of function accompanied by increases in modulators of muscle atrophy, degradation markers and plasma pro-inflammatory cytokine levels. Treatment of GWI animals with Epi yielded either a significant partial or full normalization of the above stated indicators relative to normal controls. Plasma metabolomics revealed that metabolites linked to inflammation and SkM waste pathways were dysregulated in the GWI group whereas Epi, attenuated such changes. In conclusion, in a rat model of GWI, Epi reverses detrimental changes in SkM structure including modulators of atrophy, inflammation and select plasma metabolites yielding improved function.

scholarly journals Development of muscle atrophy and loss of function in a Gulf-War illness model: underlying mechanisms

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Israel Ramirez-Sanchez ◽  
Viridiana Navarrete-Yañez ◽  
Alejandra Garate-Carrillo ◽  
Maria Loredo ◽  
Esmeralda Lira-Romero ◽  
...  
Keyword(s):  
Muscle Atrophy ◽  
Gulf War ◽  
Loss Of Function ◽  
Gulf War Illness ◽  
Underlying Mechanisms ◽  
Illness Model

scholarly journals A Subpressor Dose of Angiotensin II Elevates Blood Pressure in a Normotensive Rat Model by Oxidative Stress

2015 ◽  
pp. 153-159 ◽  
Author(s):  
M. M. GOVENDER ◽  
A. NADAR
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Angiotensin Ii ◽  
Mrna Expression ◽  
Rat Model ◽  
Wistar Rat ◽  
Control Group ◽  
Sod Activity ◽  
Male Wistar Rats ◽  
Experimental Group

Oxidative stress is an imbalance between free radicals and antioxidants, and is an important etiological factor in the development of hypertension. Recent experimental evidence suggests that subpressor doses of angiotensin II elevate oxidative stress and blood pressure. We aimed to investigate the oxidative stress related mechanism by which a subpressor dose of angiotensin II induces hypertension in a normotensive rat model. Normotensive male Wistar rats were infused with a subpressor dose of angiotensin II for 28 days. The control group was sham operated and infused with saline only. Plasma angiotensin II and H2O2 levels, whole-blood glutathione peroxidase, and AT-1a, Cu/Zn SOD, and p22phox mRNA expression in the aorta was assessed. Systolic and diastolic blood pressures were elevated in the experimental group. There was no change in angiotensin II levels, but a significant increase in AT-1a mRNA expression was found in the experimental group. mRNA expression of p22phox was increased significantly and Cu/Zn SOD decreased significantly in the experimental group. There was no significant change to the H2O2 and GPx levels. Angiotensin II manipulates the free radical-antioxidant balance in the vasculature by selectively increasing O2− production and decreasing SOD activity and causes an oxidative stress induced elevation in blood pressure in the Wistar rat.

scholarly journals Corticosterone potentiates DFP-induced neuroinflammation and affects high-order diffusion imaging in a rat model of Gulf War Illness

2018 ◽  
Vol 67 ◽  
pp. 42-46 ◽  
Author(s):  
Bang-Bon Koo ◽  
Lindsay T. Michalovicz ◽  
Samantha Calderazzo ◽  
Kimberly A. Kelly ◽  
Kimberly Sullivan ◽  
...  
Keyword(s):  
Rat Model ◽  
Diffusion Imaging ◽  
Gulf War ◽  
High Order ◽  
Gulf War Illness

Diagnosis of Gulf War Illness Using Laser-Induced Spectra Acquired from Blood Samples

2021 ◽  
pp. 000370282110420
Author(s):  
Rosalba Gaudiuso ◽  
Sirui Chen ◽  
Efi Kokkotou ◽  
Lisa Conboy ◽  
Eric Jacobson ◽  
...  
Keyword(s):  
Blood Plasma ◽  
Correct Diagnosis ◽  
Difference Spectrum ◽  
Gulf War ◽  
Classification Model ◽  
Control Group ◽  
Plasma Samples ◽  
Gulf War Illness ◽  
Breakdown Spectroscopy ◽  
The Difference

Gulf War illness (GWI) is a chronic illness with no known validated biomarkers that affects the lives of hundreds of thousands of people. As a result, there is an urgent need for the development of an untargeted and unbiased method to distinguish GWI patients from non-GWI patients. We report on the application of laser-induced breakdown spectroscopy (LIBS) to distinguish blood plasma samples from a group of subjects with GWI and from subjects with chronic low back pain as controls. We initially obtained LIBS data from blood plasma samples of four GWI patients and four non-GWI patients. We used an analytical method based on taking the difference between a mean LIBS spectrum obtained with those of GWI patients from the mean LIBS spectrum of those of the control group, to generate a “difference” spectrum for our classification model. This model was cross-validated using different numbers of differential LIBS emission peaks. A subset of 17 of the 82 atomic and ionic transitions that provided 70% of correct diagnosis was selected test in a blinded fashion using 10 additional samples and was found to yield 90% classification accuracy, 100% sensitivity, and 83.3% specificity. Of the 17 atomic and ionic transitions, eight could be assigned unambiguously to species of Na, K, and Fe.

scholarly journals Interactions between pyridostigmine bromide and stress on glutamatergic neurochemistry: Insights from a rat model of Gulf War Illness

2020 ◽  
Vol 12 ◽  
pp. 100210 ◽  
Author(s):  
V.A. Macht ◽  
J.L. Woodruff ◽  
H.E. Burzynski ◽  
C.A. Grillo ◽  
L.P. Reagan ◽  
...  
Keyword(s):  
Rat Model ◽  
Gulf War ◽  
Pyridostigmine Bromide ◽  
Gulf War Illness

scholarly journals The Effects of a Low Glutamate Dietary Intervention on Anxiety and PTSD in Veterans with Gulf War Illness (FS15-08-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Elizabeth Brandley ◽  
Anna Kirkland ◽  
Gabrielle Sarlo ◽  
John VanMeter ◽  
James Baraniuk ◽  
...  
Keyword(s):  
Anxiety Disorders ◽  
Dietary Intervention ◽  
Monosodium Glutamate ◽  
Gulf War ◽  
Rank Test ◽  
Control Group ◽  
Controlled Clinical Trial ◽  
Gulf War Illness ◽  
Double Blind ◽  
Funding Sources

Abstract Objectives Glutamate is an amino acid and also serves as the most ubiquitous neurotransmitter in the human body. Previous work has shown that dysregulated glutamatergic neurotransmission is implicated in the etiology of anxiety disorders. Objective: To examine the effect of a low glutamate dietary intervention on anxiety and Posttraumatic Stress Disorder (PTSD) in veterans with Gulf War Illness (GWI). Methods Forty veterans with GWI are being recruited for a randomized-controlled clinical trial testing the effects of a low glutamate diet on neurological symptoms. After consent, subjects complete baseline measures, then subjects are randomized to the low-glutamate diet or a wait-listed control group. For the active intervention phase, they follow a 1-month low glutamate diet and then are re-tested prior to entering a double-blind, placebo-controlled crossover challenge with monosodium glutamate (MSG) or placebo, to test for return of symptoms. Preliminary data are presented here for changes observed on the Generalized Anxiety Disorder 7-item (GAD-7) scale and the PTSD Checklist (PCL-C) after one month on the diet in subjects recruited to date. Pre-post diet scores were compared for anxiety and PTSD using a Wilcoxon Signed Rank test in SAS. Results Seventeen veterans (M = 15; F = 2) with GWI have been recruited to date (mean age = 50 ± 4 yrs). Preliminary analyses demonstrate that after one month on the diet, significant improvements were noted for anxiety (score reduced from a median (IQ range) of 9 (13) to 5 (10), p = 0.01) and for PTSD (median (IQ) score reduced from 58 (33) to 43 (28), p = 0.04). Conclusions This study suggests that consuming a low glutamate diet may improve anxiety and PTSD in veterans suffering from Gulf War Illness. More research is needed to further explore the role of dietary glutamate in anxiety disorders. Funding Sources U.S. Army Medical Research Acquisition Activity, 820 Chandler Street, Fort Detrick MD 21702-5014 is the awarding and administering acquisition office. This work was supported by the Office of the Assistant Secretary of Defense for Health Affairs, through the Gulf War Illness Research Program under Award No. W81XWH-17-1-0457. Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the Department of Defense.

scholarly journals Skeletal Muscle Response to Deflazacort, Dexamethasone and Methylprednisolone

Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 406 ◽  
Author(s):  
Alan Fappi ◽  
Juliana de Carvalho Neves ◽  
Leandro Nunes Sanches ◽  
Pedro Victor Massaroto e Silva ◽  
Guilherme Yuiti Sikusawa ◽  
...  
Keyword(s):  
Muscle Atrophy ◽  
Saline Solution ◽  
Fiber Type ◽  
Neuromuscular Diseases ◽  
Study Groups ◽  
Control Group ◽  
Cross Sectional ◽  
Genes Expression ◽  
Male Wistar Rats ◽  
Synthetic Glucocorticoids

Glucocorticoids represent some of the most prescribed drugs that are widely used in the treatment of neuromuscular diseases, but their usage leads to side effects such as muscle atrophy. However, different synthetic glucocorticoids can lead to different muscle effects, depending upon its chemical formulation. Here, we intended to demonstrate the muscle histologic and molecular effects of administering different glucocorticoids in equivalency and different dosages. Methods: Seventy male Wistar rats distributed into seven groups received different glucocorticoids in equivalency for ten days or saline solution. The study groups were: Control group (CT) saline solution; dexamethasone (DX) 1.25 or 2.5 mg/kg/day; methylprednisolone (MP) 6.7 or 13.3mg/kg/day; and deflazacort (DC) 10 or 20 mg/kg/day. At the end of the study, the animals were euthanized, and the tibialis anterior and gastrocnemius muscles were collected for metachromatic ATPase (Cross-sectional area (CSA) measurement), Western blotting (protein expression of IGF-1 and Ras/Raf/MEK/ERK pathways) and RT-PCR (MYOSTATIN, MuRF-1, Atrogin-1, REDD-1, REDD-2, MYOD, MYOG and IRS1/2 genes expression) experiments. Results: Muscle atrophy occurred preferentially in type 2B fibers in all glucocorticoid treated groups. DC on 10 mg/kg/day was less harmful to type 2B fibers CSA than other doses and types of synthetic glucocorticoids. In type 1 fibers CSA, lower doses of DC and DX were more harmful than high doses. DX had a greater effect on the IGF-1 pathway than other glucocorticoids. MP more significantly affected P-ERK1/2 expression, muscle fiber switching (fast-to-slow), and expression of REDD1 and MyoD genes than other glucocorticoids. Compared to DX and MP, DC had less of an effect on the expression of atrogenes (MURF-1 and Atrogin-1) despite increased MYOSTATIN and decreased IRS-2 genes expression. Conclusions: Different glucocorticoids appears to cause muscle atrophy affecting secondarily different signaling mechanisms. MP is more likely to affect body/muscles mass, MEK/ERK pathway and fiber type transition, DX the IGF-1 pathway and IRS1/2 expression. DC had the smallest effect on muscle atrophic response possibly due a delayed timing on atrogenes response.

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