OBJECTIVEScorpion (Hemiscorpius lepturus) stings are a public health concern in Iran, particularly in south and southwestern regions of Iran. The gold standard for the treatment of a scorpion sting is anti-venom therapy. However, immunotherapy can have serious side effects, such as anaphylactic shock (which can sometimes even lead to death). The aim of the current study was to demonstrate the protective effect of ozone against toxicity induced by Hemiscorpius lepturus (H. lepturus) venom in mice.

METHODSEight hours after the injection of ozone to the experimental design groups, the male mice were decapitated and mitochondria were isolated from five different tissues (liver, kidney, heart, brain, and spinal cord) using differential ultracentrifugation. Then, assessment of mitochondrial parameters including mitochondrial reactive oxidative species (ROS) production, mitochondrial membrane potential (MMP), ATP level, and the release of cytochrome c from the mitochondria was performed.

RESULTSOur results showed that H. lepturus venom-induced oxidative stress is related to ROS production and MMP collapse, which is correlated with cytochrome c release and ATP depletion, indicating the predisposition to the cell death signaling.

CONCLUSIONIn general, ozone therapy in moderate dose can be considered as clinically effective for the treatment of H. lepturus sting as a protective and antioxidant agent.

Animals ; Brain ; drug effects ; metabolism ; Cytochromes c ; metabolism ; Heart ; drug effects ; Kidney ; drug effects ; metabolism ; Liver ; drug effects ; metabolism ; Male ; Membrane Potential, Mitochondrial ; drug effects ; Mice ; Mice, Inbred BALB C ; Muscle, Skeletal ; drug effects ; metabolism ; Myocardium ; metabolism ; Ozone ; pharmacology ; Scorpion Venoms ; toxicity ; Scorpions ; physiology ; Spinal Cord ; drug effects ; metabolism

PURPOSE: To investigate the effect of intramuscular Botulinum toxin type A (BoNT-A) injection on gait and dynamic foot pressure distribution in children with spastic cerebral palsy (CP) with dynamic equinovarus foot. MATERIALS AND METHODS: Twenty-five legs of 25 children with CP were investigated in this study. BoNT-A was injected into the gastrocnemius (GCM) and tibialis posterior (TP) muscles under the guidance of ultrasonography. The effects of the toxin were clinically assessed using the modified Ashworth scale (MAS) and modified Tardieu scale (MTS), and a computerized gait analysis and dynamic foot pressure measurements using the F-scan system were also performed before injection and at 1 and 4 months after injection. RESULTS: Spasticity of the ankle plantar-flexor in both the MAS and MTS was significantly reduced at both 1 and 4 months after injection. On dynamic foot pressure measurements, the center of pressure index and coronal index, which represent the asymmetrical weight-bearing of the medial and lateral columns of the foot, significantly improved at both 1 and 4 months after injection. The dynamic foot pressure index, total contact area, contact length and hind foot contact width all increased at 1 month after injection, suggesting better heel contact. Ankle kinematic data were significantly improved at both 1 and 4 months after injection, and ankle power generation was significantly increased at 4 months after injection compared to baseline data. CONCLUSION: Using a computerized gait analysis and foot scan, this study revealed significant benefits of BoNT-A injection into the GCM and TP muscles for dynamic equinovarus foot in children with spastic CP.
Adolescent ; Ankle Joint ; Botulinum Toxins, Type A/administration & dosage/*pharmacology ; Cerebral Palsy/*complications/drug therapy ; Child ; Child, Preschool ; Clubfoot/*drug therapy/*etiology/physiopathology ; Female ; Foot ; Gait/*drug effects/physiology ; Humans ; Injections, Intramuscular ; Male ; Muscle Spasticity/drug therapy ; Muscle, Skeletal/diagnostic imaging ; Neuromuscular Agents/administration & dosage/*pharmacology ; Pressure ; Prospective Studies ; Treatment Outcome ; Weight-Bearing

OBJECTIVETo observe the effect of the postpone in skeletal muscle aging process of D-galactose rats by weight training and soy polypeptide supplement in 6 weeks, and discuss the initial mechanism.

METHODSixty male SD rats (three month old)were randomly assigned: 6 week control (C6,) and 6 week model (M6) 6 for each group, 12 week model (M12), big load (B12), small load (S12), peptide (P12), peptide + big load (PB12) and peptide + small load group (PS12) 8 for each group, eight fourteen month rats were taken in the natural aging group. The rats were killed by the end of 6th week and 12th week, tested the indicators.

RESULTCompare with group C6, the indicators in group M6 showed aging in different levels; Compare with group M12, weight training or soy polypeptide supplement in all intervention groups could increase the content of skeletal muscle superoxide dismutase (SOD), SOD/MDA, the serum growth hormone(GH), insulin-like growth factor-1 (IGF-I)and skeletal muscle IGF-I mRNA, decreased the malondialdehyde (MDA) content of skeletal muscle, and they had notable interaction.

CONCLUSIONRat skeletal muscle aging model can be copied successfully by D-galactose hypodermic, and go on with 6-week weight training or soy polypeptide supplement, they can postpone the skeletal muscle aging process of D-galactose rats, and the two interference way united can have more obvious effect. Its preliminary mechanism may be related to the reduction of skeletal muscle oxidative stress and lipid peroxidation, the correction of hormones and related factors metabolic disorders, the elevation of skeletal muscle IGF-I mRNA expression and so on.

Aging ; physiology ; Animals ; Galactose ; Growth Hormone ; blood ; Insulin-Like Growth Factor I ; metabolism ; Male ; Malondialdehyde ; metabolism ; Muscle, Skeletal ; drug effects ; physiology ; Physical Conditioning, Animal ; physiology ; Rats ; Rats, Sprague-Dawley ; Soybean Proteins ; pharmacology ; Soybeans ; chemistry ; Superoxide Dismutase ; metabolism

BACKGROUNDSIRT3 is an important regulator in cell metabolism, and recent studies have shown that it may be involved in the pharmacological effects of metformin. However, the molecular mechanisms underlying this process are unclear.

METHODSThe effects of SIRT3 on the regulation of oxidative stress and insulin resistance in skeletal muscle were evaluated in vitro. Differentiated L6 skeletal muscle cells were treated with 750 µmol/L palmitic acid to induce insulin resistance. SIRT3 was knocked down and overexpressed in L6 cells. SIRT3, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p65, c-Jun N-terminal kinase 1 (JNK1), and superoxide dismutase 2 (SOD2) were evaluated by Western blotting.

RESULTSOver expression of SIRT3 increased glucose uptake and decreased ROS production in L6-IR cells as well as in L6 cells. Knock-down of SIRT3 induced increased production of ROS while decreased glucose uptake in both L6 and L6-IR cells, and these effects were reversed by N-acetyl-L-cysteine (NAC). Metformin increased the expression of SIRT3 (1.5-fold) and SOD2 (2-fold) while down regulating NF-κB p65 (1.5-fold) and JNK1 (1.5-fold). Knockdown of SIRT3 (P < 0.05) reversed the metformin-induced decreases in NF-κB p65 and JNK1 and the metformin-induced increase in SOD2 (P < 0.05).

CONCLUSIONSUpregulated SIRT3 is involved in the pharmacological mechanism by which metformin promotes glucose uptake. Additionally, SIRT3 may function as an important regulator of oxidative stress and a new alternative approach for targeting insulin resistance-related diseases.

Animals ; Cell Line ; Insulin Resistance ; physiology ; Metformin ; pharmacology ; Muscle Fibers, Skeletal ; drug effects ; metabolism ; Oxidative Stress ; drug effects ; Rats ; Sirtuin 3 ; metabolism ; Transcription Factor RelA ; metabolism

PURPOSE: The purpose of this study was to examine the effect of anorexia and neuropathic pain induced by cisplatin on hindlimb muscles of rats. METHODS: Adult male Sprague-Dawley rats were divided into two groups, a cisplatin-treated group (n=10) and a control group (n=10). In the cisplatin-treated group, cisplatin at a dose of 2 mg/kg was injected intraperitoneally two times a week up to a cumulative dose of 20 mg/kg over 5 weeks, and in the control group saline (0.9% NaCl) was injected intraperitoneally at the same dose and duration as the cisplatin-treated group. At 34 days all rats were anesthetized, after which the soleus and plantaris muscles were dissected. Withdrawal threshold, body weight, food intake, activity, muscle weight, Type I and II fiber cross-sectional areas and myofibrillar protein content of the dissected muscles were determined. RESULTS: Compared with the control group, the cisplatin-treated group showed significant decreases (p<.05) in withdrawal threshold, activity, food intake, body weight, Type I and II fiber cross-sectional areas, myofibrillar protein content and weight of the soleus and plantaris muscles. CONCLUSION: Muscular atrophy in hindlimb occurs due to anorexia and neuropathic pain induced by the cisplatin treatment.
Animals ; *Anorexia ; Body Weight ; Cisplatin/*toxicity ; Eating ; Hindlimb ; Injections, Intraperitoneal ; Male ; Motor Activity ; Muscle Fibers, Skeletal/metabolism/pathology ; Muscle Proteins/metabolism ; Muscle, Skeletal/*drug effects/physiology ; Neuralgia/*chemically induced/pathology ; Rats ; Rats, Sprague-Dawley

The aim of the present study was to investigate the effect of carnitine on function of respiratory chain and metabolism of oxygen radical in mitochondria of skeletal muscle after exhaustive running in training rats. Forty male Wistar rats were randomly divided into 4 groups (n = 10): control, carnitine, training and training + carnitine groups. The training and training + carnitine groups received 6-week treadmill training, whereas carnitine and training + carnitine groups were administered intragastrically with carnitine (300 mg/kg per day, 6 d/week) for 6 weeks. After exhaustive running, all the rats from 4 groups were sacrificed to obtain quadriceps muscles samples, and muscle mitochondria were extracted by differential centrifugation. Spectrophotometric analysis was used to evaluate activities of respiratory chain complexes (RCC) I-IV, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and the content of malondialdehyde (MDA) in the skeletal muscle mitochondria. The results showed that, compared with the control group, the carnitine group exhibited increased RCCI and RCCIII activities (P < 0.05), the training + carnitine group exhibited increased RCCI, RCCIII and RCCIV activities (P < 0.05 or 0.01). Moreover, RCCIII activity in the training + carnitine group was higher than that in training group (P < 0.05). Compared with the control group, the carnitine, training and training + carnitine groups showed increased SOD activities ( P < 0.01), the carnitine and training + carnitine groups showed increased GSH-Px activities ( P < 0.01), the carnitine, training and training + carnitine groups showed increased MDA contents (P < 0.05 or 0.01). The SOD and GSH-Px activities in training + carnitine group were higher than those in training group (P < 0.01), and the MDA level in the training + carnitine group was higher than that in the carnitine and training groups (P < 0.01). These results suggest that training and carnitine can increase function of respiratory chain, antioxidation and lipid peroxidation tolerance capacity in skeletal muscle mitochondria, and the improving effects of training and carnitine are synergistic.
Animals ; Antioxidants ; metabolism ; Carnitine ; pharmacology ; Electron Transport ; Glutathione Peroxidase ; metabolism ; Male ; Malondialdehyde ; metabolism ; Mitochondria, Muscle ; drug effects ; physiology ; Muscle, Skeletal ; drug effects ; physiology ; Physical Conditioning, Animal ; Rats ; Rats, Wistar ; Reactive Oxygen Species ; metabolism ; Running ; Superoxide Dismutase ; metabolism

OBJECTIVESTo evaluate the expression profile of myoD microRNA-29 (miR-29) family in L6 myoblast differentiated to myotube of L6 myotube treated by glucose and insulin, and to further probe the molecular mechanism of myoD regulating the expression of miR-29 clusters.

METHODSThe expression of myoD and miR-29 family was detected by using real-time PCR and Western blot analysis. The potential promoter and transcription factors binding sites of miR-29 clusters were predicted by Promoter scan and transcriptional factor search. The promoter sequence of miR-29b1-a and miR-29b2-c cluster was cloned into a luciferase reporter plasmid and the regulatory effect of myoD was analyzed by using dual luciferase reporter assay. Electrophoretic mobility shift assay was further conducted to indicate the binding of myoD on specific sequence. Moreover, overexpression of myoD was achieved by a recombinant adenovirus system (Ad-myoD). L6 cells were infected with Ad-myoD and real-time PCR was conducted to analyze the expression of miR-29b and miR-29c.

RESULTSThe expression levels of myoD, miR-29a, miR-29b, and miR-29c were increased in L6 myoblast differentiated to myotube. The expression of myoD, miR-29b, and miR-29c was up-regulated in L6 myotube treated with glucose and insulin, but miR-29a depicted no significant change. Dual luciferase reporter gene assay showed that myoD functioned as a positive regulator of miR-29b2-c expression and myoD could bind to the specific sequence located at the promoter region of miR-29b2-c cluster. Enforced expression of myoD led to a marked increase of miR-29b and miR-29c levels in L6 cells.

CONCLUSIONMyoD might act as a crucial regulator of myogenesis and glucose metabolism in muscle through regulating the expression of miR-29b2-c.

Animals ; Cell Differentiation ; drug effects ; physiology ; Cell Line ; Gene Expression Regulation ; drug effects ; physiology ; Glucose ; pharmacology ; Hypoglycemic Agents ; pharmacology ; Insulin ; pharmacology ; Mice ; MicroRNAs ; biosynthesis ; genetics ; Multigene Family ; physiology ; Muscle Fibers, Skeletal ; cytology ; metabolism ; MyoD Protein ; genetics ; metabolism ; Myoblasts ; cytology ; metabolism ; Sweetening Agents ; pharmacology

OBJECTIVETo study characteristics of energy metabolism in the skeletal muscle of rats with postoperative fatigue syndrome (POFS) and the interventional effect of ginsenoside Rb1.

METHODWe chose resection of 70% of the "middle" small intestine as the rat model for POFS. Ninety-six adult male SPF SD rats were randomly divided into the control group, the model group, and the ginsenoside Rb1-treated group by body weight. And then, each group was further randomly divided into four subgroups, according to different postoperative investigated time points, such as postoperative day 1, postoperative day 3, postoperative day 7 and postoperative day 10. So the animals were divided into twelve subgroups (n = 8 in each subgroup). Rats of the control group and the model group were injected intraperitoneally with saline at the dose of 10 mL x kg(-1) one hour before the operation and once a day during the postoperative days. Rats of the ginsenoside Rb1-treated group were administered 10 mg x kg(-1) ginsenoside Rb1 by the same method. The skeletal muscles were sampled on postoperative day 1, 3, 7 and 10. The contents of ATP, ADP, AMP in skeletal muscles were determined by HPLC, and the activities of Na(+)-K(+)-ATPase and Ca(2+)-ATPase were investigated by colorimetry.

RESULTCompared with the control group, the content of ATP in skeletal muscle of rats of the model group decreased significantly on postoperative day 3 (P < 0.05), while the content of ADP significantly increased on postoperative day 7 and 10 (P < 0.05). The activity of Na(+)-K(+)-AT-Pase decreased on postoperative day 3 and 7 (P < 0.05), and the activity of Ca(2+)-ATPase decreased on postoperative day 7. After supplement of ginsenoside Rb1, on the investigated time points, all the negative changes of the indicators discovered above were significantly adjusted (P < 0.05) in rats of the ginsenoside Rb1-treated group, while no significant differences were investigated.

CONCLUSIONDuring a certain period of postoperative time, the activity of energy metabolism is depressed in the skeletal muscle of rats with POFS, but it can be improved by supplement of ginsenoside Rb1.

Animals ; Calcium-Transporting ATPases ; physiology ; Energy Metabolism ; drug effects ; Fatigue ; drug therapy ; metabolism ; Ginsenosides ; pharmacology ; therapeutic use ; Male ; Muscle, Skeletal ; metabolism ; Postoperative Complications ; drug therapy ; metabolism ; Rats ; Rats, Sprague-Dawley ; Sodium-Potassium-Exchanging ATPase ; physiology ; Syndrome

This study was conducted to evaluate whether the composition of carbohydrate or fat diet affects insulin resistance by measuring the muscle glucose transport rate. Both high-sucrose and high-starch diet with or without high-fat decreased insulin-stimulated glucose transport, but there were no significant differences among groups. Calorie intake in both high-sucrose and high-starch diet groups was higher than in chow group. The high-fat high-sucrose diet induced decrease in insulin-stimulated glucose transport was partially improved by supplement with fish oil. Calorie intake in high-fat high-sucrose and fish oil supplemented groups was higher than in chow group. The decreased insulin-stimulated glucose transport was accompanied by the increase in visceral fat mass, plasma triglyceride and insulin levels. These changes were improved by the supplement with fish oil. These results demonstrate that the composition of fat in diet is clearly instrumental in the induction of muscle insulin resistance. However, in high carbohydrate diet, it is likely that the amount of calorie intake may be a more important factor in causing insulin resistance than the composition of carbohydrate. Thus, the compositions of carbohydrate and fat in diet differentially affect on muscle insulin resistance.
Animals ; Blood Glucose/metabolism ; Body Weight ; Diet ; Dietary Carbohydrates/*pharmacology ; Dietary Fats/*pharmacology ; Dietary Supplements ; Energy Intake/drug effects ; Fish Oils/pharmacology ; Insulin/blood ; Insulin Resistance/*physiology ; Intra-Abdominal Fat/drug effects/metabolism ; Male ; Muscle, Skeletal/*drug effects/physiology ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the effect of ascorbic acid (VC) on relaxation of ex vivo Bufo gastrocnemius during sustained isometric contraction.

METHODSDynamic tension of the muscle was recorded under constant voltage stimulation within 7.0 min at 2 s intervals. The rest tension and relaxation rate of the muscle was obtained by weighted fitting to the relaxation process of tension <90% of its peak with a mono-exponential model to characterize the muscular relaxation.

RESULTSVC at 2.0 mmol/L alone or in combination with the inhibitors of the antixoidation enzymes (surperoxide dismutase, glutathione peroxidase and catalase) resulted in negligible alterations in the muscular relaxation kinetics. VC combined with the inhibitor of surperoxide dismutase resulted in significantly lowered relaxation rate while increased rest tension, but VC with the inhibitor of either catalase or glutathione peroxidase showed negligible action. VC combined with the inhibitors of all the 3 enzymes also caused significant effect on the muscular relaxation kinetics, which was similar the effect of VC with superoxide dismutase inhibitor.

CONCLUSIONVC at high concentration may result in oxidative toxicity to the biological system rich in transitional metal ion complexes but with low antioxidation capacity by causing superoxide-mediated oxidative damages.

Animals ; Ascorbic Acid ; pharmacology ; Bufonidae ; Electric Stimulation ; In Vitro Techniques ; Isometric Contraction ; drug effects ; Muscle Relaxation ; drug effects ; Muscle, Skeletal ; drug effects ; physiology