scholarly journals Improved Tetanic Force and Mitochondrial Calcium Homeostasis by Astaxanthin Treatment in Mouse Skeletal Muscle

Antioxidants ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 98 ◽  
Author(s):  
Sztretye ◽  
Singlár ◽  
Szabó ◽  
Angyal ◽  
Balogh ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Calcium Homeostasis ◽  
Inhibitory Effect ◽  
Calcium Transients ◽  
Muscle Performance ◽  
Control Group ◽  
Mitochondrial Calcium ◽  
Tetanic Force

Background: Astaxanthin (AX) a marine carotenoid is a powerful natural antioxidant which protects against oxidative stress and improves muscle performance. Retinol and its derivatives were described to affect lipid and energy metabolism. Up to date, the effects of AX and retinol on excitation-contraction coupling (ECC) in skeletal muscle are poorly described. Methods: 18 C57Bl6 mice were divided into two groups: Control and AX supplemented in rodent chow for 4 weeks (AstaReal A1010). In vivo and in vitro force and intracellular calcium homeostasis was studied. In some experiments acute treatment with retinol was employed. Results: The voltage activation of calcium transients (V50) were investigated in single flexor digitorum brevis isolated fibers under patch clamp and no significant changes were found following AX supplementation. Retinol shifted V50 towards more positive values and decreased the peak F/F0 of the calcium transients. The amplitude of tetani in the extensor digitorum longus was significantly higher in AX than in control group. Lastly, the mitochondrial calcium uptake was found to be less prominent in AX. Conclusion: AX supplementation increases in vitro tetanic force without affecting ECC and exerts a protecting effect on the mitochondria. Retinol treatment has an inhibitory effect on ECC in skeletal muscle.

scholarly journals Assessing the Potential of Nutraceuticals as Geroprotectors on Muscle Performance and Cognition in Aging Mice

Antioxidants ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1415
Author(s):  
Zoltán Singlár ◽  
Péter Szentesi ◽  
János Fodor ◽  
Ágnes Angyal ◽  
László Csernoch ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Spatial Memory ◽  
Calcium Homeostasis ◽  
Muscle Force ◽  
Force Production ◽  
Muscle Performance ◽  
Learning Ability ◽  
Control Group ◽  
Mitochondrial Calcium ◽  
Krill Oil

Aging and frailty are associated with a decline in muscle force generation, which is a direct consequence of reduced muscle quantity and quality. Among the leading contributors to aging is the generation of reactive oxygen species, the byproducts of terminal oxidation. Their negative effects can be moderated via antioxidant supplementation. Krill oil and astaxanthin (AX) are nutraceuticals with a variety of health promoting, geroprotective, anti-inflammatory, anti-diabetic and anti-fatigue effects. In this work, we examined the functional effects of these two nutraceutical agents supplemented via pelleted chow in aging mice by examining in vivo and in vitro skeletal muscle function, along with aspects of intracellular and mitochondrial calcium homeostasis, as well as cognition and spatial memory. AX diet regimen limited weight gain compared to the control group; however, this phenomenon was not accompanied by muscle tissue mass decline. On the other hand, both AX and krill oil supplementation increased force production without altering calcium homeostasis during excitation-contraction coupling mechanism or mitochondrial calcium uptake processes. We also provide evidence of improved spatial memory and learning ability in aging mice because of krill oil supplementation. Taken together, our data favors the application of antioxidant nutraceuticals as geroprotectors to improve cognition and healthy aging by virtue of improved skeletal muscle force production.

Inhibitory Effect of Resveratrol on the Pharmacokinetics of Ticagrelor in Vivo and Vitro

2021 ◽  
Author(s):  
Peng Wang ◽  
Xiao-Xia Hu ◽  
Ying-hui Li ◽  
Nan-Yong Gao ◽  
Guo-quan Chen ◽  
...  
Keyword(s):  
Rat Liver ◽  
Liver Microsomes ◽  
In Vitro Study ◽  
Inhibitory Effect ◽  
Control Group ◽  
Rat Liver Microsomes ◽  
Sprague Dawley ◽  
Group B

This study was to evaluate the effect of resveratrol on the pharmacokinetics of ticagrelor in rats and the metabolism of ticagrelor in human CYP3A4 and liver microsomes. Eighteen Sprague-Dawley rats were randomly divided into three groups: group A (control group), group B (50mg/kg resveratrol), and group C (150mg/kg resveratrol ). After 30 minutes administration of resveratrol, a single dose of ticagrelor (18mg/kg) was administered orally. The vitro experiment was performed to examine the influence of resveratrol on ticagrelor metabolism in CYP3A4*1, human, and rat liver microsomes. Serial biological samples were assayed by validated UHPLC-MS/MS methods. In vivo study, the AUC and Cmax of ticagrelor in group B and C appeared to be significantly higher than the control group, while Vz/F and CLz/F of ticagrelor in group B and C were significantly decreased. In vitro study, resveratrol exhibited an inhibitory effect on CYP3A4*1, human and rat liver microsomes. The IC50 values of resveratrol were 56.75μM，69.07μM and 14.22μM, respectively. Our results indicated that resveratrol had a inhibitory effect on the metabolism of ticagrelor in vitro and vivo. It should be paid more attention to the clinical combination of resveratrol with ticagrelor and ticagrelor plasma concentration should be monitored to avoid the occurrence of adverse reaction.

scholarly journals α-Glucosidase Inhibitory, Anti-Oxidant, and Anti-Hyperglycemic Effects of Euphorbia nivulia–Ham. in STZ-Induced Diabetic Rats

Dose-Response ◽  
2020 ◽  
Vol 18 (3) ◽  
pp. 155932582093942
Author(s):  
Muhammad Younus ◽  
Muhammad Mohtasheem ul Hasan ◽  
Khalil Ahmad ◽  
Ali Sharif ◽  
Hafiz Muhammad Asif ◽  
...  
Keyword(s):  
High Performance ◽  
Wistar Rat ◽  
Inhibitory Effect ◽  
Diabetic Rats ◽  
In Vivo Studies ◽  
Control Group ◽  
Control Drug ◽  
Antidiabetic Effects

In this study, we aimed to investigate the antidiabetic effects of Euphorbia nivulia (En), native to Cholistan Desert area of Bahawalpur, Pakistan. First, we performed high-performance liquid chromatography analysis and found that this plant contains ferulic acid, gallic acid, quercetin, benzoic acid, polyphenols, and flavonoids. Then, we performed in vitro and in vivo studies to assess its effects on diabetic Wistar rat model. The experiments were performed and compared with control drug glibenclamide. The 70% hydroalcoholic extract of En exhibited 97.8% in vitro α-glucosidase inhibitory effect at a dose of 1.0 mg/mL. We orally administered the extract of En and control drug to the streptozotocin (STZ)-induced diabetic rats and analyzed its antidiabetic effects. We found that the extract of En with a dose of 500 mg/kg/body weight exhibited significant effect to reduce blood glucose in STZ-induced rats as compared with the control group ( P < .001). Our histological data also showed that the extract significantly improved the histopathology of pancreas. Collectively, both in vitro and in vivo studies revealed that En possesses α-glucosidase inhibitory, antioxidant, and anti-hyperglycemic effect in STZ-induced diabetic rats.

scholarly journals Effects of potassium deficiency on growth and protein synthesis in skeletal muscle and the heart of rats

1989 ◽  
Vol 62 (2) ◽  
pp. 269-284 ◽  
Author(s):  
Inge Dôrup ◽  
Torben Clausen
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Muscle Protein ◽  
Control Level ◽  
Inhibitory Effect ◽  
Potassium Deficiency ◽  
Skeletal Muscle Protein ◽  
K Deficiency

The effects of potassium deficiency on growth, K content and protein synthesis have been compared in 4–13-week-old rats. When maintained on K-deficient fodder (1 mmol/kg) rats ceased to grow within a few days, and the incorporation of [3H]leucine into skeletal muscle protein in vivo was reduced by 28–38%. Pair-feeding experiments showed that this inhibition was not due to reduced energy intake. Following 14 d on K-deficient fodder, there was a further reduction (39–56 %) in the incorporation of [3H]leucine into skeletal muscle protein, whereas the incorporation into plasma, heart and liver proteins was not affected. The accumulation of the non-metabolized amino acid α-aminoisobutyric acid in the heart and skeletal muscles was not reduced. The inhibitory effect of K deficiency on 3H-labelling of muscle protein was seen following intraperitoneal (10–240 min) as well as intravenous (10 min) injection of [3H]leucine. In addition, the incorporation of [3H]phenylalanine into skeletal muscle protein was reduced in K-depleted animals. Following acute K repletion in vivo leading to complete normalization of muscle K content, the incorporation of [3H]leucine into muscle protein showed no increase within 2 h, but reached 76 and 104% of the control level within 24 and 72 h respectively. This was associated with a rapid initial weight gain, but normal body-weight was not reached until after 7 weeks of K repletion. Following 7 d on K-deficient fodder the inhibition of growth and protein synthesis was closely correlated with the K content of the fodder (1–40 mmol/kg) and significant already at modest reductions in muscle K content. In vitro experiments with soleus muscle showed a linear relationship between the incorporation of [3H]leucine into muscle protein and K content, but the sensitivity to cellular K deficiency induced in vitro was much less pronounced than that induced in vivo. Thus, in soleus and extensor digitorum longus (EDL) muscles prepared from K-deficient rats, the incorporation of [3H]leucine was reduced by 30 and 47 % respectively. This defect was completely restored by 24 h K repletion in vivo. It is concluded that in the intact organism protein synthesis and growth are very sensitive to dietary K deficiency and that this can only partly be accounted for by the reduction in cellular K content per se. The observations emphasize the need for adequate K supplies to ensure optimum utilization of food elements for protein synthesis and growth.

scholarly journals Experimental Application of Sage in Rabbit Husbandry

2008 ◽  
Vol 77 (4) ◽  
pp. 581-588 ◽  
Author(s):  
R. Szabóová ◽  
A. Lauková ◽  
Ľ. Chrastinová ◽  
M. Simonová ◽  
V. Strompfová ◽  
...  
Keyword(s):  
Inhibitory Effect ◽  
Negative Influence ◽  
Feed Consumption ◽  
Control Group ◽  
Coagulase Negative Staphylococci ◽  
E Coli ◽  
Commercial Feed ◽  
Experimental Group

Salvia spp. belongs to the Labiatae family and is characterized by antimicrobial and antiinflammatory effect. The aim of this study was to test its in vitro and in vivo inhibitory effect against bacteria as well as to find an alternative possibility to use sage in the rabbit ecosystem examining biochemical, zootechnical and inmunological indicators, compared to the commercial feed mixture Xtract. Using the sage extract in in vitro tests, its inhibitory effect was noted. Under in vivo conditions, in the experimental group with sage (EG1), reduction of Pseudomonas-like sp. (p < 0.01) and E. coli (p < 0.01) was noted after 7 days of sage application compared to the control group CG2 (with Robenidin) as well as after 21 days of sage extract application, when the reduction of coagulase-negative staphylococci (p < 0.01) was detected (in comparison with the experimental group-EG2, Xtract group). In the caecum of rabbits from EG1, higher values of lactic, acetic and butyric acids were noted. The values of propionic acid were not influenced. Biochemical indicators were not influenced; however, the values of GSH Px were lower in EG1 compared to EG2. Higher phagocytic activity (18%) was noted in EG1 than in EG2 (13%) after 21 days of additives application. The reduction of Eimeria sp. oocysts was demonstrated in EG1 (sage group) after 7 days of sage application comparing to CG2 (217 OPG to 566 OPG). The animals in both experimental groups achieved higher feed consumption and weight gain, lower mortality compared to both controls. Neither of the additives had a negative influence on the health status and growth performance of rabbits.

scholarly journals PO-252 Effect of acupuncture intervention on the changes of cytoplasmic and mitochondrial Ca2+ concentration following eccentric contractions in rat skeletal muscle

2018 ◽  
Vol 1 (5) ◽  
Author(s):  
Aishan Liu ◽  
Fangming Liu ◽  
Xuelin Zhang ◽  
Yarong Wang ◽  
Mei Kong ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Electrical Stimulation ◽  
Fluorescent Imaging ◽  
Eccentric Contractions ◽  
Rat Skeletal Muscle ◽  
Tetanic Force ◽  
Acupuncture Intervention ◽  
Stimulation Group

  Objective The purpose of this study was to evaluate the effect of acupuncture intervention on the changes of cytoplasmic and mitochondrial Ca2+ concentration following eccentric contractions (ECC) in rat skeletal muscle. Methods 24 healthy male Wistar rats were randomly divided into 4 groups: control group (C, n=6)、electrical stimulation group (E, n=6)、electrical stimulation group with acupuncture intervention (EA, n=6)、electrical stimulation group with acupuncture +TRP channel inhibitor Gd3+ (EAI, n=6). The animal model of eccentric induced skeletal muscle injury was established by electrical stimulation on spinotrapezius muscle of anaesthetised rats in vivo, that is to say, the intact spinotrapezius muscle of adult Wistar rats was exteriorized, and tetanic eccentric contractions (100 Hz, 10 sets of 50 contractions) were elicited by electrical stimulation during synchronized muscle stretch of 10% resting muscle length. Cytoplasmic Ca2+ accumulation were determined by loading the muscle with fura 4-AM using fluorescent imaging in vivo, and mitochondrial Ca2+ concentration were determined by loading the muscle with fura 2-AM using fluorescent imaging in vitro, and recorded changes of muscle maximum tetanic force. Results (1) In vivo, compared with the C , cytoplasmic Ca2+ accumulation increased more rapidly during ECC in the E (P < 0.001). Acupuncture intervention significantly reduced cytosolic Ca2+ accumulation in the EA compared with the E (P < 0.01), and we discovered that muscle deformation generated by acupuncture intervention induced a robust Ca2+ spark response confined in close spatial proximity to the sarcolemmal membrane in intact muscle fibers. Although no significant differences between the EA and EAI, Gd3+ abolished the majority of cytoplasmic Ca2+ accumulation decrease during ECC in the EAI and a robust Ca2+ spark response disappeared compared with the EA. (2) In vitro, compared with the C, mitochondrial Ca2+ concentration did not elevations in MCC in the E. EA cytoplasmic Ca2+ increased rapidly above the C and E (P < 0.01), respectively, but EAI significantly attenuated the increases in  mitochondrial Ca2+ concentration compared with the EA (P < 0.01). (3). Compared with the C , maximum tetanic force was significantly lower in the E after ECC (P < 0.01). EA maximum tetanic force increased rapidly compared with the E after ECC (P < 0.05), but EAL abolished the majority maximum tetanic force increase after ECC (P < 0.05). Conclusions (1)Eccentric contraction caused cytoplasmic Ca2+ accumulation, but  mitochondrial Ca2+ concentration decrease. (2)Acupuncture can effectively reduce cytosolic Ca2+ overload, following by mitochondrial Ca2+ concentration increase , which in turn abnormally high cytoplasmic Ca2+ levels are buffed by the mitochondria, and improved muscle function, and the effect was associated to the TRP channels.  

scholarly journals Isolation Purification and Partial Characterization of Antisnake Venom Plant Peptide (BRS-P19) from Bauhinia rufescens (LAM FAM) Seed as Potential Alternative to Serum-Based Antivenin

2020 ◽  
pp. 18-26
Author(s):  
I. Sani ◽  
A.A. Umar ◽  
S.A. Jiga ◽  
F. Bello ◽  
A. Abdulhamid ◽  
...  
Keyword(s):  
Antioxidant Enzymes ◽  
Research Work ◽  
Gel Filtration ◽  
Inhibitory Effect ◽  
Untreated Group ◽  
Control Group ◽  
In Vivo Experiments ◽  
Potential Alternative

Several studies have been reported on active peptides isolated from some medicinal plants, which were effective inhibitors against snake venom induced toxicities. Hence, the aim of this research work was to isolate, purify and characterize an antisnake venom plant peptide from Bauhinia rufescens seed that can serve as potential alternative to serum-based antivenins. B. rufescens seed was collected, duly identified, authenticated and processed. The peptide was isolated from the seed and purified using gel filtration chromatography and SDS-PAGE and then named as BRS-P19. Venom Phospholipase A2 (VPLA2) was used for the study and was isolated from Naja nigricollis venom. Albino mice of both sexes were used for in vivo experiments. They were divided into seven (7) groups of three (3) mice each. Group 1 served as normal control, group 2 were injected with VPLA2 only, group 3 and 4 were injected with VPLA2 then treated with BRS-P19 at doses of 0.2 and 0.4 mg/kg b.w. respectively, while mice in group 5 were injected with VPLA2 then treated with standard antivenin, group 6 and 7 were injected with VPLA2 followed by administration of ascorbic acid and α-tocopherol respectively. In all the groups, hepatic and renal levels of reactive oxygen species (ROS), lipid peroxidation (MDA) and activities of antioxidant enzymes were determined. The results showed that, the BRS-P19 has molecular weight of ~19kD. Its percentage in vitro inhibitory effect against VPLA2 was 91.85 ± 0.32%. For the in vivo study, the animals treated with 0.4 mg/kg b.w. of the BRS-P19 showed a significant (P<0.05) decrease in the hepatic and renal ROS and MDA levels when compared with the VPLA2 untreated group. But, the activities of the antioxidant enzymes in all the treated groups were significantly (P<0.05) increased by the BRS-P19 at 0.4 mg/kg b.w. when compared to the VPLA2 untreated group. Based on these findings, it has been established that, BRS-P19 has antisnake venom effect through inhibition of VPLA2 and antioxidant activity as the possible mechanisms of action.

scholarly journals Trimetazidine Attenuates Dexamethasone-Induced Muscle Atrophy via Inhibiting NLRP3/GSDMD Pathway-Mediated Pyroptosis

2020 ◽  
Author(s):  
Li Wang ◽  
Ming-Qing He ◽  
Xi-Yu Shen ◽  
Kang-Zhen Zhang ◽  
Can Zhao ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Ring Finger ◽  
Muscle Performance ◽  
Skeletal Muscle Atrophy ◽  
C2c12 Myotubes ◽  
High Dose ◽  
Therapeutic Compound

Skeletal muscle atrophy is one of the major side effects of high dose or sustained usage of glucocorticoids. Pyroptosis is a novel form of pro-inflammatory programmed cell death that may contribute to skeletal muscle injury. Trimetazidine, a well-known anti-anginal agent, can also improve skeletal muscle performance both in human and mice. We here showed that dexamethasone induced atrophy, evidenced by the increase of muscle atrophy F-box (Atrogin-1) and muscle ring finger 1 (MuRF1) expression , and the decrease of myotube diameter in C2C12 myotubes. Dexamethasone also induced pyroptosis, indicated by upregulated pyroptosis-related protein NLRP3, Caspase-1 and GSDMD. Knockdown of NLRP3 or GSDMD attenuated dexamethasone-induced myotube pyroptosis and atrophy. Trimetazidine administration ameliorated dexamethasone-induced muscle atrophy both in vivo and in vitro. Moreover, trimetazidine improved exercise tolerance, as evidenced by increased running distance and running time, as well as increased skeletal muscle mass in dexamethasone-treated mice. Mechanically, trimetazidine could reverse dexamethasone-induced activation of pyroptosis both in C2C12 myotubes and in mice. Taken together, our present study demonstrated that NLRP3/GSDMD pathway-mediated pyroptosis was involved in dexamethasone-induced skeletal muscle atrophy. Trimetazidine could partially alleviate dexamethasone-induced skeletal muscle atrophy, and increase the diameter of C2C12 myotubes via inhibiting pyroptosis. Thus, trimetazidine might be a potential therapeutic compound for the prevention of muscle atrophy in glucocorticoid-treated patients.

scholarly journals The effect of obesity on the contractile performance of isolated mouse soleus, EDL, and diaphragm muscles

2017 ◽  
Vol 122 (1) ◽  
pp. 170-181 ◽  
Author(s):  
Jason Tallis ◽  
Cameron Hill ◽  
Rob S. James ◽  
Val M. Cox ◽  
Frank Seebacher
Keyword(s):  
Skeletal Muscle ◽  
Muscle Function ◽  
Isometric Force ◽  
Muscle Performance ◽  
Muscle Quality ◽  
Control Group ◽  
Protein Kinase Activity ◽  
Negative Cycle ◽  
Contractile Performance

Obesity affects the major metabolic and cellular processes involved in skeletal muscle contractility. Surprisingly, the effect of obesity on isolated skeletal muscle performance remains unresolved. The present study is the first to examine the muscle-specific changes in contractility following dietary-induced obesity using an isolated muscle work-loop (WL) model that more closely represents in vivo muscle performance. Following 16-wk high-calorific feeding, soleus (SOL), extensor digitorum longus (EDL), and diaphragm (DIA) were isolated from female (CD-1) mice, and contractile performance was compared against a lean control group. Obese SOL produced greater isometric force; however, isometric stress (force per unit muscle area), absolute WL power, and normalized WL power (watts per kilogram muscle mass) were unaffected. Maximal isometric force and absolute WL power of the EDL were similar between groups. For both EDL and DIA, isometric stress and normalized WL power were reduced in the obese groups. Obesity caused a significant reduction in fatigue resistance in all cases. Our findings demonstrate a muscle-specific reduction in contractile performance and muscle quality that is likely related to in vivo mechanical role, fiber type, and metabolic profile, which may in part be related to changes in myosin heavy chain expression and AMP-activated protein kinase activity. These results infer that, beyond the additional requirement of moving a larger body mass, functional performance and quality of life may be further limited by poor muscle function in obese individuals. As such, a reduction in muscle performance may be a substantial contributor to the negative cycle of obesity. NEW & NOTEWORTHY The effect of obesity on isolated muscle function is surprisingly underresearched. The present study is the first to examine the effects of obesity on isolated muscle performance using a method that more closely represents real-world muscle function. This work uniquely establishes a muscle-specific profile of mechanical changes in relation to underpinning mechanisms. These findings may be important to understanding the negative cycle of obesity and in designing interventions for improving weight status.

scholarly journals In Vitro and In Vivo Activities of Newer Fluoroquinolones against Vibrio vulnificus

2002 ◽  
Vol 46 (11) ◽  
pp. 3580-3584 ◽  
Author(s):  
Hung-Jen Tang ◽  
Ming-Chung Chang ◽  
Wen-Chien Ko ◽  
Kun-Yen Huang ◽  
Chih-Lung Lee ◽  
...  
Keyword(s):  
Vibrio Vulnificus ◽  
Survival Rates ◽  
Treated Group ◽  
Inhibitory Effect ◽  
Clinical Strain ◽  
Control Group ◽  
Dilution Method ◽  
Agar Dilution Method

ABSTRACT The MICs of six fluoroquinolones as well as minocycline and cefotaxime for 46 clinical isolates of Vibrio vulnificus were determined by the agar dilution method. All the drugs tested had good activities against all isolates, with the MICs at which 90% of the isolates tested were inhibited (MIC90s) by five of the fluoroquinolones ranging between 0.03 and 0.06 μg/ml. The MIC90 of lomefloxacin, on the other hand, was 0.12 μg/ml. Time-kill studies were conducted with these agents and a clinical strain of V. vulnificus, VV5823. When approximately 5 × 105 CFU of V. vulnificus/ml was incubated with any one of the above-mentioned six fluoroquinolones at concentrations of two times the MIC, there was an inhibitory effect on V. vulnificus that persisted for more than 48 h with no noted regrowth. The efficacies of the fluoroquinolones were further evaluated in vivo in the mouse model of experimental V. vulnificus infection and compared to the efficacy of a combination therapy using cefotaxime plus minocycline. With an inoculum of 1.5 × 107 CFU, 28 (87.5%) of 32 mice in the cefotaxime-minocycline-treated group survived and 29 (91%) of the 32 mice in the moxifloxacin-treated group survived while none of the 32 mice in the control group did. With an inoculum of 3.5 × 107 CFU, the difference in survival rates among groups of 15 mice treated with levofloxacin (13 of 15), moxifloxacin (10 of 15), gatifloxacin (10 of 15), sparfloxacin (11 of 15), ciprofloxacin (12 of 15), or lomefloxacin (10 of 15) was not statistically significant while none of the 15 mice treated with saline survived. We concluded that the newer fluoroquinolones as single agents are as effective as the cefotaxime-minocycline combination in inhibiting V. vulnificus both in vitro and in vivo.

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