Dexmedetomidine reduces isoflurane-induced neuroapoptosis through regulating BDNF and proBDNF

Abstract Background: It is well-acknowledged that Isoflurane induces neuroapoptosis in neonatal rats. Dexmedetomidine, as an α2-adrenergic agonist, was previously demonstrated to provide neuroprotection when administered during isoflurane anesthesia. Our study aims to investigate the mechanisms concerning the neuroprotective effect of dexmedetomidine from the alterations of BDNF,ERK, and JNK signals in the hippocampal region. Methods: Neonatal Sprague-Dawley rats at postnatal day 7 were assigned into Control group, Isoflurane group, Dexmedetomidine group and Inhibitor group. After exposed to 2% isoflurane in 40% of oxygen mixed with nitrogen for 4h, the hippocampus tissues were separated and critical signal pathway proteins of BDNF, proBDNF, JNK, ERK, and caspase 3 were detected. Results: Neuroapoptosis was triggered by Isoflurane with the increased expression of caspase 3 and TUNEL-positive cells. This effect was reversed by dexmedetomidine accompanying with up-regulation of BDNF and phospho-ERK and down-regulation of proBDNF and phospho-JNK. Conclusions: This study revealed that dexmedetomidine pretreatment can attenuate neurotoxicity caused by isoflurane in neonatal rats by regulating BDNF, proBDcNF, ERK, and JNK, which would provide a new target for neuroprotection.

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Sulodexide Protects Contrast-Induced Nephropathy in Sprague-Dawley Rats

Cellular Physiology and Biochemistry ◽

10.1159/000452575 ◽

2016 ◽

Vol 40 (3-4) ◽

pp. 621-632 ◽

Cited By ~ 11

Author(s):

Qing Zhao ◽

Jianyong Yin ◽

Zeyuan Lu ◽

Yiwei Kong ◽

Guangyuan Zhang ◽

...

Keyword(s):

Oxidative Stress ◽

Caspase 3 ◽

Vehicle Group ◽

Control Group ◽

Therapeutic Effects ◽

Protective Effects ◽

Sprague Dawley ◽

Contrast Induced Nephropathy ◽

Sprague Dawley Rats ◽

Hk2 Cells

Background: Sulodexide is a powerful antithrombin agent with reno-protective property. However, whether it has beneficial effects on Contrast-Induced Nephropathy (CIN) remained elusive. In the current study, we evaluated the therapeutic effects of Sulodexide on CIN and investigated the potential mechanisms. Methods: CIN model was induced by intravenous injection of indomethacin, followed by Ioversol and L-NAME. Sprague-Dawley rats were divided into 4 groups: control group, CIN group, CIN+vehicle group (CIN rats pretreated with vehicle) and CIN+ Sulodexide (CIN rats pretreated with Sulodexide). Sulodexide or an equivalent volume of vehicle was intravenously delivered 30 min before the induction of CIN. All the animals were sacrificed at 24h after CIN and tissues were harvested to evaluate renal injury, kidney oxidative stress and apoptosis levels. Plasma antithrombin III (ATIII) activities were also measured. Results: Compared to the untreated CIN group, improved renal function, reduced tubular injury, decreased levels of oxidative stress and apoptosis were observed in CIN rats receiving Sulodexide injection. In addition, we also found that ATIII activity was significantly higher in Sulodexide-administered group than that in vehicle-injected CIN rats. For in vitro studies, HK2 cells were exposed to Ioversol and the cyto-protective effects of Sulodexide were also determined. Sulodexide pretreatment protected HK2 cells against the cytotoxicity of Ioversol via inhibiting caspase-3 activity. Preincubation with Sulodexide could also attenuate H2O2-induced increases in ROS, apoptosis and caspase-3 levels. Conclusions: Taken together, Sulodexide could protect against CIN through activating ATIII, and inhibiting oxidative stress, inflammation and apoptosis.

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Hypaconitine confers protection on ketamine-induced neuronal injury in neonatal rat brain via a mechanism involving PI3K/Akt/Bcl-2 pathway

Tropical Journal of Pharmaceutical Research ◽

10.4314/tjpr.v18i9.8 ◽

2021 ◽

Vol 18 (9) ◽

pp. 1839-1844

Author(s):

Junbao Liu ◽

Yubo Hu ◽

Linlin Li ◽

Longyun Li

Keyword(s):

Cell Viability ◽

Caspase 3 ◽

Neuroprotective Effect ◽

Neuronal Cells ◽

Specific Inhibitor ◽

Neuronal Cell ◽

Neuronal Injury ◽

Neonatal Rat ◽

Control Group ◽

Neonatal Rats

Purpose: To investigate the neuroprotective effect of hypaconitine against ketamine-induced neuronal injury in the brains of neonatal rats, and the underlying mechanism of action. Methods: Seven day-old Sprague-Dawley pups weighing 15.0 to 20.0 g (mean weight = 17.5 ± 2.5 g), and aged 7 days were used for this study. The pups were sacrificed, and their forebrains isolated and used to prepare cell suspensions. The isolated cells were treated with ketamine (100 µM) or varied concentrations of hypaconitine (0.1 – 2 µM) or LY294002 (10 µM). The cells were trypsinized and cultured at 37 °C in 10 % fetal bovine serum (FBS) supplemented Dulbecco's modified Eagle's medium (DMEM) in a humidified incubator containing 5 % CO2. Cell viability was determined using MTT assay, while TUNEL assay was used to determine the extent of apoptosis in the cells. The expressions of pAkt, Bcl-2 and caspase-3 were determined using Western blotting. Results: There were only few viable cells in the ketamine-treated group, and cell viability was significantly and dose-dependently increased in hypaconitine-treated groups (p < 0.05). The extent of apoptosis was significantly higher in ketamine-treated cells than in control cells, but treatment with hypaconitine significantly reduced the number of apoptotic cells (p < 0.05). However, in the presence of LY294002 (a PI3K-specific inhibitor), the effect of hypaconitine on neuronal cell apoptosis was significantly reversed (p < 0.05). The expressions of p-Akt and Bcl-2 were significantly down-regulated while the expression of caspase-3 was significantly upregulated in ketamine-treated neuronal cells, when compared with control group (p < 0.05). However, in cells treated with hypaconitine, the expressions of p-Akt and Bcl-2 were significantly upregulated, while the expression of caspase-3 was significantly down-regulated (p < 0.05). Treatment of neuronal cells with hypaconitine in the presence of LY294002 significantly reversed the effect of hypaconitine on the expressions of p-Akt, Bcl-2 and caspase-3 (p < 0.05). Conclusion: These results suggest that hypaconitine ameliorates ketamine-induced neuronal injury in neonatal rats via a mechanism involving the PI3K/Akt/Bcl-2 pathway.

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IMPACT OF ZOLEDRONATE BISPHOSPHONATE GEL IN VIRGIN COCONUT OIL ON THE INCREASE OF OSTEOCLAST APOPTOSIS

International Journal of Applied Pharmaceutics ◽

10.22159/ijap.2017.v9s2.07 ◽

2018 ◽

Vol 9 ◽

pp. 24

Author(s):

Carolin Parlina ◽

Erni H Purwaningsih ◽

Ahmad Aulia Jusuf ◽

Retno Widayati

Keyword(s):

Buccal Mucosa ◽

Caspase 3 ◽

Coconut Oil ◽

Control Group ◽

Sprague Dawley ◽

Emulsion Gel ◽

Sprague Dawley Rats ◽

The Impact ◽

Experimental Group ◽

Osteoclast Apoptosis

Objective: This study aimed to show the impact of the ZOL in VCO gel (Ge-ZOL) on the extent of osteoclasts apoptosis.Methods: The study used 27 Sprague-Dawley rats which were divided into three groups: Nine rats in the experimental group were given 40 µg of Ge-ZOL, nine rats in the control group were given VCO emulsion gel without ZOL (Ge-), and nine rats in the normal group were not given any treatment. The gel was applied to the buccal mucosa using a cotton bud for 2 min at hour of 0, 4, and 8 on days 0, 1, 2, 3, and 4. The rats were sacrificed on days 1, 3, and 5, and then, evaluated by immunohistochemical caspase-3 staining.Result: The number of apoptotic osteoclast cells in the experimental group was significantly higher than in the control and normal groups (p<0.05). The number of apoptotic osteoclast cells in the experimental group on the day 1 was significantly higher than on the days 3 and 5 (p<0.001).Conclusion: The application of Ge-ZOL to the buccal mucosa proven to improve the number of apoptotic osteoclast cells in the experimental group on the day 1, and this number was higher than on the days 3 and 5.

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Possible Association Between DHEA and PKCε in Hepatic Encephalopathy Amelioration: A Pilot Study

Frontiers in Veterinary Science ◽

10.3389/fvets.2021.695375 ◽

2021 ◽

Vol 8 ◽

Author(s):

Alessandro Di Cerbo ◽

Luca Roncati ◽

Carlotta Marini ◽

Gianluca Carnevale ◽

Manuela Zavatti ◽

...

Keyword(s):

Hepatic Encephalopathy ◽

Neuroprotective Effect ◽

Brain Area ◽

Control Group ◽

Sprague Dawley ◽

Kinase C ◽

Sprague Dawley Rats ◽

Protein Kinase C Epsilon ◽

Neuronal Functions ◽

And Control

Objective: Hepatic encephalopathy (HE) is a neuropsychiatric syndrome caused by liver failure and by an impaired neurotransmission and neurological function caused by hyperammonemia (HA). HE, in turn, decreases the phosphorylation of protein kinase C epsilon (PKCε), contributing to the impairment of neuronal functions. Dehydroepiandrosterone (DHEA) exerts a neuroprotective effect by increasing the GABAergic tone through GABAA receptor stimulation. Therefore, we investigated the protective effect of DHEA in an animal model of HE, and the possible modulation of PKCε expression in different brain area.Methods: Fulminant hepatic failure was induced in 18 male, Sprague–Dawley rats by i.p. administration of 3 g/kg D-galactosamine, and after 30 min, a group of animals received a subcutaneous injection of 25 mg/kg (DHEA) repeated twice a day (3 days). Exploratory behavior and general activity were evaluated 24 h and 48 h after the treatments by the open field test. Then, brain cortex and cerebellum were used for immunoblotting analysis of PKCε level.Results: DHEA administration showed a significant improvement of locomotor activity both 24 and 48 h after D-galactosamine treatment (****p < 0.0001) but did not ameliorate liver parenchymal degeneration. Western blot analysis revealed a reduced immunoreactivity of PKCε (*p < 0.05) following D-galactosamine treatment in rat cortex and cerebellum. After the addition of DHEA, PKCε increased in the cortex in comparison with the D-galactosamine-treated (***p < 0.001) and control group (*p < 0.05), but decreased in the cerebellum (*p < 0.05) with respect to the control group. PKCε decreased after treatment with NH4Cl alone and in combination with DHEA in both cerebellum and cortex (****p < 0.0001). MTS assay demonstrated the synergistic neurotoxic action of NH4Cl and glutamate pretreatment in cerebellum and cortex along with an increased cell survival after DHEA pretreatment, which was significant only in the cerebellum (*p < 0.05).Conclusion: An association between the DHEA-mediated increase of PKCε expression and the improvement of comatose symptoms was observed. PKCε activation and expression in the brain could inhibit GABA-ergic tone counteracting HE symptoms. In addition, DHEA seemed to ameliorate the symptoms of HE and to increase the expression of PKCε in cortex and cerebellum.

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Modulation of renal ischemia/reperfusion in rats by a combination of ischemic preconditioning and adipose-derived mesenchymal stem cells (ADMSCs)

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2016-0018 ◽

2016 ◽

Vol 94 (9) ◽

pp. 936-946 ◽

Cited By ~ 7

Author(s):

Abdelaziz M. Hussein ◽

Nashwa Barakat ◽

Amira Awadalla ◽

Mahmoud M. Gabr ◽

Sherry Khater ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Ischemic Preconditioning ◽

Caspase 3 ◽

Ischemia Reperfusion ◽

Treated Group ◽

Renal Ischemia ◽

Control Group ◽

Sprague Dawley ◽

Sprague Dawley Rats

The present study investigated the effects of combination of ischemic preconditioning (Ipre) and adipose-derived mesenchymal stem cells (ADMSCs) on renal ischemia–reperfusion (I–R) injury in rats. 90 male Sprague Dawley rats were divided into 5 equal groups; sham operated, control (45 min left renal ischemia), Ipre group as control group with 3 cycles of Ipre just before renal ischemia, ADMSCs-treated group (as control with ADMSCs 106 cells in 0.1 mL via penile vein 60 min before ischemia time), and Ipre + ADMSCs group as ADMCs group with 3 cycles of Ipre. Ipre and ADMSCs groups showed significant decrease in serum creatinine and blood urea nitrogen (BUN) and caspase-3 and CD45 expression in kidney and significant increase in HIF-1α, SDF-1α, CD31, and Ki67 expressions in kidney compared with the control group (p < 0.05). Moreover, the Ipre + ADMSCs group showed significant decrease in serum BUN and caspase-3 and CD45 expression in kidney with significant increase in HIF-1α, SDF-1α, CD31, and Ki67 expression in kidney compared with the Ipre and ADMCs groups (p < 0.05). We concluded that Ipre potentiates the renoprotective effect of ADMSCs against renal I/R injury probably by upregulation of HIF-1α, SDF-1α, CD31, and Ki67 and downregulation of caspase-3 and CD45.

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The Effect of Xialiqi Capsule on Testosterone-Induced Benign Prostatic Hyperplasia in Rats

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2018/5367814 ◽

2018 ◽

Vol 2018 ◽

pp. 1-9 ◽

Cited By ~ 2

Author(s):

Hongcai Cai ◽

Guowei Zhang ◽

Zechen Yan ◽

Xuejun Shang

Keyword(s):

Benign Prostatic Hyperplasia ◽

Caspase 3 ◽

Positive Control ◽

Prostatic Hyperplasia ◽

Control Group ◽

Sprague Dawley ◽

Elderly Men ◽

Sprague Dawley Rats ◽

Increased Activity ◽

Anti Inflammation

Benign prostatic hyperplasia (BPH) is common among elderly men, of which inflammation, oxidative stress, proliferative, and apoptotic changes play important roles. Xialiqi (XLQ) capsule, a traditional Chinese herbal formula, is used as a potential drug in treating BPH. This study aims to evaluate the therapeutic effect of XLQ capsule on testosterone propionate- (TP-) induced BPH in rats. Fifty male Sprague-Dawley rats were randomly divided into 5 groups: sham control, BPH model, high and low dose of XLQ, and finasteride as a positive control group. All groups were treated with appropriate drugs/normal saline for 28 consecutive days. Prostate weights were recorded; histopathological changes and content of IL-8, TNF-α, DHT, SOD, MDA, caspase-3, and PCNA of the prostate were determined. Animals with BPH demonstrated significantly increased prostate weights and prostate index, higher levels of IL-8, TNF-α, DHT, MDA, and PCNA, but lower activity of SOD and reduced expression of caspase-3. After treatment with XLQ, significant reductions of prostate weights, prostate index, IL-8, TNF-α, DHT, MDA, and PCNA, increased activity of SOD, and higher level of caspase-3 were shown. The present study indicates that XLQ can effectively prevent the development of TP-induced BPH model through mechanisms of anti-inflammation, antioxidation, antiproliferation, and proapoptosis.

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Intermittent hypoxia inhibits mandibular cartilage growth with reduced TGF-β and SOX9 expressions in neonatal rats

Scientific Reports ◽

10.1038/s41598-020-80303-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Kochakorn Lekvijittada ◽

Jun Hosomichi ◽

Hideyuki Maeda ◽

Haixin Hong ◽

Chidsanu Changsiripun ◽

...

Keyword(s):

Bone Mineral ◽

Intermittent Hypoxia ◽

Hyaline Cartilage ◽

Body Weight Gain ◽

Mandibular Condyle ◽

Neonatal Rats ◽

Sprague Dawley ◽

Cartilage Growth ◽

Condylar Cartilage ◽

Sprague Dawley Rats

AbstractIntermittent hypoxia (IH) has been associated with skeletal growth. However, the influence of IH on cartilage growth and metabolism is unknown. We compared the effects of IH on chondrocyte proliferation and maturation in the mandibular condyle fibrocartilage and tibial hyaline cartilage of 1-week-old male Sprague–Dawley rats. The rats were exposed to normoxic air (n = 9) or IH at 20 cycles/h (nadir, 4% O2; peak, 21% O2; 0% CO2) (n = 9) for 8 h each day. IH impeded body weight gain, but not tibial elongation. IH also increased cancellous bone mineral and volumetric bone mineral densities in the mandibular condylar head. The mandibular condylar became thinner, but the tibial cartilage did not. IH reduced maturative and increased hypertrophic chondrocytic layers of the middle and posterior mandibular cartilage. PCR showed that IH shifted proliferation and maturation in mandibular condyle fibrocartilage toward hypertrophic differentiation and ossification by downregulating TGF-β and SOX9, and upregulating collagen X. These effects were absent in the tibial growth plate hyaline cartilage. Our results showed that neonatal rats exposed to IH displayed underdeveloped mandibular ramus/condyles, while suppression of chondrogenesis marker expression was detected in the growth-restricted condylar cartilage.

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Skeletal Muscle Metabolomic Responses to Endurance and Resistance Training in Rats under Chronic Unpredictable Mild Stress

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18041645 ◽

2021 ◽

Vol 18 (4) ◽

pp. 1645

Author(s):

Xiangyu Liu ◽

Xiong Xue ◽

Junsheng Tian ◽

Xuemei Qin ◽

Shi Zhou ◽

...

Keyword(s):

Resistance Exercise ◽

Endurance Exercise ◽

Field Tests ◽

Treadmill Running ◽

Control Group ◽

Mild Stress ◽

Chronic Unpredictable Mild Stress ◽

Sprague Dawley ◽

Exercise Interventions ◽

Sprague Dawley Rats

The objectives of this study were to compare the antidepressant effects between endurance and resistance exercise for optimizing interventions and examine the metabolomic changes in different types of skeletal muscles in response to the exercise, using a rat model of chronic unpredictable mild stress (CUMS)-induced depression. There were 32 male Sprague-Dawley rats randomly divided into a control group (C) and 3 experimental groups: CUMS control (D), endurance exercise (E), and resistance exercise (R). Group E underwent 30 min treadmill running, and group R performed 8 rounds of ladder climbing, 5 sessions per week for 4 weeks. Body weight, sucrose preference, and open field tests were performed pre and post the intervention period for changes in depressant symptoms, and the gastrocnemius and soleus muscles were sampled after the intervention for metabolomic analysis using the 1H-NMR technique. The results showed that both types of exercise effectively improved the depression-like symptoms, and the endurance exercise appeared to have a better effect. The levels of 10 metabolites from the gastrocnemius and 13 metabolites from the soleus of group D were found to be significantly different from that of group C, and both types of exercise had a callback effect on these metabolites, indicating that a number of metabolic pathways were involved in the depression and responded to the exercise interventions.

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Curcumin Reduces Neuroinflammation and Improves the Impairments of Anesthetics on Learning and Memory by Regulating the Expression of miR-181a-5p

NeuroImmunoModulation ◽

10.1159/000514548 ◽

2021 ◽

pp. 1-9

Author(s):

Guizhen Liu ◽

Yuchuan Sun ◽

Fei Liu

Keyword(s):

Cognitive Impairment ◽

Protective Effect ◽

Learning And Memory ◽

Cognitive Dysfunction ◽

Inflammatory Cytokines ◽

Neuroprotective Effect ◽

Morris Water Maze Test ◽

Sprague Dawley ◽

Protein Levels ◽

Sprague Dawley Rats

Objective: The purpose of this study was to explore the role of curcumin (Cur) in isoflurane (ISO)-induced learning and memory dysfunction in Sprague-Dawley rats and further elucidate the mechanism of the protective effect produced by Cur. Methods: Rat models of cognitive impairment were established by inhaling 3% ISO. The Morris water maze test was used to assess the cognitive function of rats. ELISA and qRT-PCR were used to analyze the protein levels of pro-inflammatory cytokines and expression levels of miR-181a-5p, respectively. Results: Cur significantly improved the ISO-induced cognitive dysfunction in rats and alleviated the ISO-induced neuroinflammation. miR-181a-5p was overexpressed in ISO-induced rats, while Cur treatment significantly reduced the expression of miR-181a-5p. Overexpression of miR-181a-5p promoted the cognitive impairment and the release of inflammatory cytokines and reversed the neuroprotective effect of Cur. Conclusion: Cur has a protective effect on ISO-induced cognitive dysfunction, which may be achieved by regulating the expression of miR-181a-5p.

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Comparison of Bax and Caspase-3 Protein Expression in Liver Cells following UVB Irradiation for 7 days and Treatment of Pimpinella alpina Molk during 7 and 15 days

Bangladesh Journal of Medical Science ◽

10.3329/bjms.v19i2.45011 ◽

2020 ◽

Vol 19 (2) ◽

pp. 296-303

Author(s):

Eni Widayati ◽

Taufiqurrachman Nasihun ◽

Azizah Hikma Savitri ◽

Nurina Tyagita

Keyword(s):

Protein Expression ◽

Caspase 3 ◽

Medical Science ◽

Liver Cells ◽

Male Rats ◽

Control Group ◽

Sprague Dawley ◽

Control Group Design ◽

Uvb Irradiation ◽

The Difference

Objective: The effect of Pimpinela alpina Molk (PaM) on decrease in Bax and Caspase-3 protein expression in liver cells apoptosis have been proven. However, the difference result between 7 and 15 days treatment duration of PaM need to be confirmed. This study aimed to confirm that treatment of PaM during 15 days is more effective decreasing Bax and Caspase-3 protein expression in liver cells following UVB irradiation. Methods: In the post test only control group design, 35 Sprague Dawley male rats, 300 gram body weight were divided into two arms, consisting of three groups respectively. First arm comprise Neg-7, PaM7-100, and PaM7-150. Second arm comprise Neg-15, PaM15-100, and PaM15-150. Nor-G was added as normal control neither exposed to UVB nor PaM treatment. In negative group was only radiated to UVB and PaM groups were exposed to UVB and treatment with 100, and 150 mg PaM per oral for 7 and 15 days respectively. At day 8 (first arm) and 16 (second arm), liver organ was taken and Bax and Caspase-3 protein expression assessed by Immunohistochemical staining method. Result: Post Hoc LSD analysis indicated that Bax and Caspase-3 protein expression in PaM15-100 and PaM15-150 was significant lower compared to that of Nor-G, PaM7-100, and PaM7-150, p < 0.05. Conclusion: Ttreatment of PaM with doses 100 and 150 mg for 15 days was better in decreasing Bax and Caspase-3 protein expression of liver cells following UVB irradiation. Bangladesh Journal of Medical Science Vol.19(2) 2020 p.296-303

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