Role of Cannabidiol and Tetrahydrocannabivarin on Paclitaxel-Induced Neuropathic Pain in Rodents

2021 ◽  
Author(s):  
Anil Kumar Kalvala ◽  
Arvind Bagde ◽  
Peggy Arthur ◽  
Sunil Kumar Surapaneni ◽  
Ramesh Nimma ◽  
...  
Keyword(s):  
Primary Cultures ◽  
P38 Map Kinase ◽  
Control Group ◽  
Cb1 Receptors ◽  
Neuroprotective Effects ◽  
Sd Rats ◽  
Protein Expressions ◽  
Behavioral Parameters ◽  
Neurobehavioral Symptoms

Abstract The purpose of this study was to investigate the neuroprotective effects of phytocannabinoids, synthetic cannabidiol (CBD) and tetrahydrocannabivarin (THCV) and their combination on taxol induced peripheral neuropathy (PIPN) in mice. Briefly, six groups of C57BL/6J mice (n = 6) were used. PTX (8 mg/kg/day, i.p.) was given to the mice on days 1, 3, 5, and 7 to induce neuropathy. Mice were evaluated for their behavioral parameters and also at the end of the study, DRG collected from the animals were subjected to RNA sequence and westernblot analysis. Further, immunocytochemistry and mitochondrial functional assays were performed on cultured DRGs derived from SD rats. The combination of CBD and THCV improved thermal and mechanical neurobehavioral symptoms in mice by two folds as compared to individual treatments. KEGG (RNA Sequencing) identified P38-MAPK, AMPK, and PI3K-AKT pathways as potential CBD and THCV therapeutic targets. In PTX-treated animals, the expression of p-AMPK, SIRT1, NRF2, HO1, SOD2, and catalase was significantly reduced (p<0.001), whereas the expression of PI3K, p-AKT, p-P38 MAP kinase, BAX, TGF-, NLRP3 inflammasome, and caspase 3 was significantly increased (p<0.001) when compared to control group. In reversing these protein expressions, combination therapy outperformed single therapies. CBD and THCV treatment increased AMPK, Catalase, and Complex I expression while decreasing mitochondrial superoxides in DRG primary cultures. In mice and DRG primary cultures, WAY100135 and rimonabant inhibited the effects of CBD and THCV by blocking 5 HT1A and CB1 receptors. In conclusion, entourage effect of CBD and THCV combination against PIPN appears to protect neurons in mice by modulating 5HT1A and CB1 receptors, respectively.

scholarly journals Calcium Export from Neurons and Multi-Kinase Signaling Cascades Contribute to Ouabain Neuroprotection in Hyperhomocysteinemia

Biomolecules ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 1104
Author(s):  
Maria A. Ivanova ◽  
Arina D. Kokorina ◽  
Polina D. Timofeeva ◽  
Tatiana V. Karelina ◽  
Polina A. Abushik ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Primary Cultures ◽  
Glutamate Excitotoxicity ◽  
Neuroprotective Effects ◽  
Mediated Effects ◽  
Mitochondrial Inner Membrane ◽  
Rat Cortical Neurons ◽  
Proteinkinase C ◽  
Apoptosis Related Protein

Pathological homocysteine (HCY) accumulation in the human plasma, known as hyperhomocysteinemia, exacerbates neurodegenerative diseases because, in the brain, this amino acid acts as a persistent N-methyl-d-aspartate receptor agonist. We studied the effects of 0.1–1 nM ouabain on intracellular Ca2+ signaling, mitochondrial inner membrane voltage (φmit), and cell viability in primary cultures of rat cortical neurons in glutamate and HCY neurotoxic insults. In addition, apoptosis-related protein expression and the involvement of some kinases in ouabain-mediated effects were evaluated. In short insults, HCY was less potent than glutamate as a neurotoxic agent and induced a 20% loss of φmit, whereas glutamate caused a 70% decrease of this value. Subnanomolar ouabain exhibited immediate and postponed neuroprotective effects on neurons. (1) Ouabain rapidly reduced the Ca2+ overload of neurons and loss of φmit evoked by glutamate and HCY that rescued neurons in short insults. (2) In prolonged 24 h excitotoxic insults, ouabain prevented neuronal apoptosis, triggering proteinkinase A and proteinkinase C dependent intracellular neuroprotective cascades for HCY, but not for glutamate. We, therefore, demonstrated here the role of PKC and PKA involving pathways in neuronal survival caused by ouabain in hyperhomocysteinemia, which suggests existence of different appropriate pharmacological treatment for hyperhomocysteinemia and glutamate excitotoxicity.

scholarly journals Neuraminidase1 Inhibitor Protects Against Doxorubicin-Induced Cardiotoxicity via Suppressing Drp1-Dependent Mitophagy

2021 ◽  
Vol 9 ◽  
Author(s):  
Yating Qin ◽  
Chao Lv ◽  
Xinxin Zhang ◽  
Weibin Ruan ◽  
Xiangyu Xu ◽  
...  
Keyword(s):  
Mitochondrial Fission ◽  
Subsequent Development ◽  
Control Group ◽  
Protective Effects ◽  
Sprague Dawley ◽  
Beneficial Effects ◽  
Myocardial Apoptosis ◽  
Sd Rats ◽  
Cardio Protection

Anthracyclines, such as doxorubicin (DOX), are among the effective chemotherapeutic drugs for various malignancies. However, their clinical use is limited by irreversible cardiotoxicity. This study sought to determine the role of neuraminidase 1 (NEU1) in DOX-induced cardiomyopathy and the potential cardio-protective effects of NEU1 inhibitor oseltamivir (OSE). Male Sprague–Dawley (SD) rats were randomized into three groups: control, DOX, and DOX + OSE. NEU1 was highly expressed in DOX-treated rat heart tissues compared with the control group, which was suppressed by OSE administration. Rats in the DOX + OSE group showed preserved cardiac function and were protected from DOX-induced cardiomyopathy. The beneficial effects of OSE were associated with the suppression of dynamin-related protein 1 (Drp1)-dependent mitochondrial fission and mitophagy. In detail, the elevated NEU1 in cardiomyocytes triggered by DOX increased the expression of Drp1, which subsequently enhanced mitochondrial fission and PINK1/Parkin pathway-mediated mitophagy, leading to a maladaptive feedback circle towards myocardial apoptosis and cell death. OSE administration selectively inhibited the increased NEU1 in myocardial cells insulted by DOX, followed by reduction of Drp1 expression, inhibition of PINK1 stabilization on mitochondria, and Parkin translocation to mitochondria, thus alleviating excessive mitochondrial fission and mitophagy, alleviating subsequent development of cellular apoptotic process. This work identified NEU1 as a crucial inducer of DOX-induced cardiomyopathy by promoting Drp1-dependent mitochondrial fission and mitophagy, and NEU1 inhibitor showed new indications of cardio-protection against DOX cardiotoxicity.

scholarly journals Effects of Xiaoyaosan on Stress-Induced Anxiety-Like Behavior in Rats: Involvement of CRF1 Receptor

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
You-Ming Jiang ◽  
Xiao-Juan Li ◽  
Zhen-Zhi Meng ◽  
Yue-Yun Liu ◽  
Hong-Bo Zhao ◽  
...  
Keyword(s):  
Basolateral Amygdala ◽  
Immobilization Stress ◽  
Elevated Plus Maze ◽  
Antidepressant Activity ◽  
Control Group ◽  
Sd Rats ◽  
Surgery Group ◽  
Artificial Cerebrospinal Fluid ◽  
Plus Maze

Background. Compared with antidepressant activity of Xiaoyaosan, the role of Xiaoyaosan in anxiety has been poorly studied.Objective. To observe the effects of Xiaoyaosan on anxiety-like behavior induced by chronic immobilization stress (CIS) and further explore whether these effects were related to CRF1R signaling.Methods. Adult male SD rats were randomly assigned to five groups (n=12): the nonstressed control group, vehicle-treated (saline, p.o.) group, Xiaoyaosan-treated (3.854 g/kg, p.o.) group, vehicle-treated (surgery) group, and antalarmin-treated (surgery) group. Artificial cerebrospinal fluid (0.5 μL/side) or CRF1R antagonist antalarmin (125 ng/0.5 μL, 0.5 μL/side) was bilaterally administered into the basolateral amygdala in the surgery groups. Except for the nonstressed control group, the other four groups were exposed to CIS (14 days, 3 h/day) 30 minutes after treatment. On days 15 and 16, all animals were subjected to the elevated plus-maze (EPM) and novelty suppressed feeding (NSF) test. We then examined the expression of CRF1R, pCREB, and BDNF in the amygdala.Results. Chronic pretreatment with Xiaoyaosan or antalarmin significantly reversed elevated anxiety-like behavior and the upregulated level of CRF1R and BDNF in the amygdala of stressed rats. pCREB did not differ significantly among the groups.Conclusions. These results suggest that Xiaoyaosan exerts anxiolytic-like effects in behavioral tests and the effects may be related to CRF1R signaling in the amygdala.

scholarly journals Dietary Oleocanthal Supplementation Prevents Inflammation and Oxidative Stress in Collagen-Induced Arthritis in Mice

Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 650
Author(s):  
Tatiana Montoya ◽  
Marina Sánchez-Hidalgo ◽  
María Luisa Castejón ◽  
María Ángeles Rosillo ◽  
Alejandro González-Benjumea ◽  
...  
Keyword(s):  
Virgin Olive Oil ◽  
Extra Virgin Olive Oil ◽  
Protective Effects ◽  
Collagen Induced Arthritis ◽  
Neuroprotective Effects ◽  
Tnf Α ◽  
Protein Expressions ◽  
Ifn Γ ◽  
Preventive Role

Oleocanthal (OLE), a characteristic and exclusive secoiridoid of Oleoaceae family, is mainly found in extra virgin olive oil (EVOO). Previous studies have reported its antioxidant, anti-inflammatory, antimicrobial, anticancer and neuroprotective effects. Since the pathogenesis of rheumatoid arthritis (RA) involves inflammatory and oxidative components, this study was designed to evaluate the preventive role of dietary OLE-supplemented effects in collagen-induced arthritis (CIA) murine model. Animals were fed with a preventive OLE-enriched dietary during 6 weeks previous to CIA induction and until the end of experiment time. At day 43 after first immunization, mice were sacrificed: blood was recollected and paws were histological and biochemically processed. Dietary OLE prevented bone, joint and cartilage rheumatic affections induced by collagen. Levels of circulatory matrix metalloproteinase (MMP)-3 and pro-inflammatory cytokines (IL-6, IL-1β, TNF-α, IL-17, IFN-γ) were significantly decreased in secoiridoid fed animals. Besides, dietary OLE was able to diminish COX-2, mPGES-1 and iNOS protein expressions and, also, PGE2 levels. The mechanisms underlying these protective effects could be related to Nrf-2/HO-1 axis activation and the inhibition of relevant signaling pathways including JAK-STAT, MAPKs and NF-κB, thus controlling the production of inflammatory and oxidative mediators. Overall, our results exhibit preliminary evidences about OLE, as a novel dietary tool for the prevention of autoimmune and inflammatory disorders, such as RA.

Tryptophan-Niacin Metabolism in Rat with Puromycin Aminonucleoside-Induced Nephrosis

2006 ◽  
Vol 76 (1) ◽  
pp. 28-33 ◽  
Author(s):  
Yukari Egashira ◽  
Shin Nagaki ◽  
Hiroo Sanada
Keyword(s):  
Body Weight ◽  
Urinary Excretion ◽  
Enzyme Activities ◽  
Treated Group ◽  
Control Group ◽  
Puromycin Aminonucleoside ◽  
Low Level ◽  
Key Enzyme

We investigated the change of tryptophan-niacin metabolism in rats with puromycin aminonucleoside PAN-induced nephrosis, the mechanisms responsible for their change of urinary excretion of nicotinamide and its metabolites, and the role of the kidney in tryptophan-niacin conversion. PAN-treated rats were intraperitoneally injected once with a 1.0% (w/v) solution of PAN at a dose of 100 mg/kg body weight. The collection of 24-hour urine was conducted 8 days after PAN injection. Daily urinary excretion of nicotinamide and its metabolites, liver and blood NAD, and key enzyme activities of tryptophan-niacin metabolism were determined. In PAN-treated rats, the sum of urinary excretion of nicotinamide and its metabolites was significantly lower compared with controls. The kidneyα-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD) activity in the PAN-treated group was significantly decreased by 50%, compared with the control group. Although kidney ACMSD activity was reduced, the conversion of tryptophan to niacin tended to be lower in the PAN-treated rats. A decrease in urinary excretion of niacin and the conversion of tryptophan to niacin in nephrotic rats may contribute to a low level of blood tryptophan. The role of kidney ACMSD activity may be minimal concerning tryptophan-niacin conversion under this experimental condition.

The Use of Posterior Pericardiotomy Technique to Prevent Postoperative Pericardial Effusion in Cardiac Surgery

2012 ◽  
Vol 15 (2) ◽  
pp. 84 ◽  
Author(s):  
Canturk Cakalagaoglu ◽  
Cengiz Koksal ◽  
Ayse Baysal ◽  
Gokhan Alici ◽  
Birol Ozkan ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Heart Surgery ◽  
Artery Bypass ◽  
Pericardial Tamponade ◽  
Anxiety Level ◽  
Control Group ◽  
Echocardiographic Study ◽  
Number Of Patients ◽  
Hospital Stays

<p><b>Aim:</b> The goal was to determine the effectiveness of the posterior pericardiotomy technique in preventing the development of early and late pericardial effusions (PEs) and to determine the role of anxiety level for the detection of late pericardial tamponade (PT).</p><p><b>Materials and Methods:</b> We divided 100 patients randomly into 2 groups, the posterior pericardiotomy group (n = 50) and the control group (n = 50). All patients undergoing coronary artery bypass grafting surgery (CABG), valvular heart surgery, or combined valvular and CABG surgeries were included. The posterior pericardiotomy technique was performed in the first group of 50 patients. Evaluations completed preoperatively, postoperatively on day 1, before discharge, and on postoperative days 5 and 30 included electrocardiographic study, chest radiography, echocardiographic study, and evaluation of the patient's anxiety level. Postoperative causes of morbidity and durations of intensive care unit and hospital stays were recorded.</p><p><b>Results:</b> The 2 groups were not significantly different with respect to demographic and operative data (<i>P</i> > .05). Echocardiography evaluations revealed no significant differences between the groups preoperatively; however, before discharge the control group had a significantly higher number of patients with moderate, large, and very large PEs compared with the pericardiotomy group (<i>P</i> < .01). There were 6 cases of late PT in the control group, whereas there were none in the pericardiotomy group (<i>P</i> < .05). Before discharge and on postoperative day 15, the patients in the pericardiotomy group showed significant improvement in anxiety levels (<i>P</i> = .03 and .004, respectively). No differences in postoperative complications were observed between the 2 groups.</p><p><b>Conclusion:</b> Pericardiotomy is a simple, safe, and effective method for reducing the incidence of PE and late PT after cardiac surgery. It also has the potential to provide a better quality of life.</p>

The Estimation of prostate specific antigen (PSA) concentrations in patients with prostatitis by fully automated ELISA technique.

2020 ◽  
Vol 3 (11) ◽  
pp. 1100-1104
Author(s):  
Hussein Naeem Aldhaheri ◽  
Ihsan Edan AlSaimary ◽  
Murtadha Mohammed ALMusafer
Keyword(s):  
Personal Information ◽  
Receptor Gene ◽  
Specific Antigen ◽  
Gene Clusters ◽  
Control Group ◽  
P Value ◽  
Group Data ◽  
Elisa Technique ◽  
And Control

      The Aim of this study was to determine Immunogenetic expression of  Toll-like receptor gene clusters related to prostatitis, to give acknowledge about Role of TLR in prostatitis immunity in men from Basrah and Maysan provinces. A case–control study included 135 confirmed prostatitis patients And 50 persons as a control group. Data about age, marital status, working, infertility, family history and personal information like (Infection, Allergy, Steroid therapy, Residency, Smoking, Alcohol Drinking, Blood group, Body max index (BMI) and the clinical finding for all patients of Prostatitis were collected. This study shows the effect of PSA level in patients with prostatitis and control group, with P-value <0.0001 therefore the study shows a positive significant between elevated PSA levels and Prostatitis.

Effectiveness Of Toilet Training Education On Mother's Behavior And Toddler Age Toilet Training Ability (18-36 Months)

2020 ◽  
Vol 5 (2) ◽  
pp. 49-55
Author(s):  
Hafiko Andresni ◽  
Zahtamal Zahtamal ◽  
Winda Septiani ◽  
Mitra Mitra ◽  
Lita Lita
Keyword(s):  
Sampling Technique ◽  
T Test ◽  
The Body ◽  
Toilet Training ◽  
Wilcoxon Test ◽  
Control Group ◽  
Maternal Knowledge ◽  
Control Group Design ◽  
Significant Difference

ABSTRACT Toilet training is an effort to train children to be able to control and urinate (BAK) and defecate (BAB). Toilet training is one of the main tasks of children at toddler age. Toilet training is one of the main tasks of children in toddler age which is very important to be done to create independence in children in controlling BAK and BAB and children know the parts of the body and their functions. Data in 2012 shows that ± 60% of parents do not teach toilet training to children from an early age. The aim of the study was to find out the effectiveness of toilet training education on maternal behavior and toilet skills in toddler age training (18-36 months). The study was conducted in July-August 2018. This type of quantitative research used the design of the Quasy pretest and posttest experiment with non-equivalent control group design. Samples were 36 mothers and 36 children with purposive sampling technique. Data analysis used Paired t test, Wilcoxon test, Man-Whitney test an Independent t test. The results showed that toilet training education through lecture methods, modules and maze games was more effective than toilet training education through lecture and leaflet methods on children's knowledge and abilities. Conversely, for the role of mothers in supervision there is no significant difference in effectiveness. Health education is recommended in health promotion programs to increase maternal knowledge, the role of mothers and the ability of toilet training children independently. Keywords: Toilet training, Lecture method, Module, Maze game, Leaflet, Knowledge, Role of mother, Children's ability.

Membangun Fondasi Keilmuan Ekonomi Islam: Telaah Metodologi Muhammad Akram Khan

2017 ◽  
Vol 1 (2) ◽  
pp. 152-170
Author(s):  
Ahmad Ubaidillah
Keyword(s):  
General Theory ◽  
Empirical Evidence ◽  
Inductive Method ◽  
Ethical Values ◽  
Institutional Conditions ◽  
Faith Based ◽  
Behavioral Parameters ◽  
Science Methodology ◽  
Islamic Society

Throughout my experience in tracking down and reading books on faith-based economics, in this case Islam, there are no books that specifically list the title of "Islamic economics". If there is, it is only initiated or introduced. Most books coming down to us still use the titles starting with the word, for example, system, concept, principle, or the doctrine of Islamic economics. Why do the authors of the book Islamic economics seem not dared to give his book title with label "science"? I presume that Islamic economics has not been considered as a science. In building a science, methodology is required. Islamic Economics also requires a well-established methodology to build the foundation of science. The study answers questions; how is methodology which is offered by Muhammad Akram Khan to build Islamic economics. The method used in this research is the study of literature with qualitative approach.The result of study concludes that Khan offers methodology of Islamic economics, if summarized, written as follows: First, Islamic economics uses a framework derived from the texts of divinity (revelation). Second, Islamic economics uses the inductive method, which gives witness to the truth or falsity assumptions and predictions about the two criteria of rationality and empirical evidence. Third, Islamic economy is built on ethical values ​​such as justice, virtue, moderation, sacrifice, caring for others, in the analysis, as behavioral parameters. Fourth, Islamic economics is a normative discipline. Islamic Economics investigates ways and means to change the existing economy with Islamic economy. Fifth, Islamic economics ask different questions with conventional economics. Its attention is on welfare (falah) human and creating social and institutional conditions that maximize falah in society. Clearly, Islamic economics strongly supports research programs that help maximize falah. Furthermore, Khan elaborates several issues related to the methodology that often appears in the forum of Islamic economists. There are some problems that Khan proposes, they are the interaction with modern economics, the role of revelation, assuming ideal Islamic society, and the general theory of Islamic economics.

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