The effect of 1 Hz, 30 mT pulsed magnetic fields on young adult rat femoral metaphyseal bone thickness was assessed. Ten same litter, female Wistar rats were studied; five of them underwent 30 min magnetic stimulation sessions for 20 consecutive days. The anterior and posterior cortical, as well as trabecular bone transverse thicknesses were measured. The results obtained under clear field microscopy in stimulated and control histological cuts were (in microm) 398 +/- 32 versus 260 +/- 22 (P = 0.002), 380 +/- 68 versus 252 +/- 21 (P = 0.03), and 168 +/- 11 versus 112 +/- 11 (P = 0.002), respectively. The transcranial magnetic stimulation system, approved for human therapy, generates pulsed electromagnetic fields, which induce a significant thickness increase in cortical and trabecular in vivo stimulated bone tissues. This is the first time this effect in healthy animals is shown.
Aims/Introduction
Myopathy is a common complication of any diabetes type, consisting in failure to preserve mass and muscular function. Oxidative stress has been considered one of the main causes for this condition. This study aimed to search if Nicorandil, a KATP channel opener, could protect slow‐ and fast‐twitch diabetic rat muscles from oxidative stress, and to unveil its possible mechanisms.
Materials and Methods
Diabetes was induced in male Wistar rats by applying intraperitoneally streptozotocin (STZ) at 100 mg/kg doses. Nicorandil (3 mg/kg/day) was administered along 4 weeks. An insulin tolerance test and assessment of fasting blood glucose (FBG), TBARS, reduced (GSH), and disulfide (GSSG) glutathione levels, GSH/GSSG ratio, and mRNA expression of glutathione metabolism‐related genes were performed at end of treatment in soleus and gastrocnemius muscles.
Results
Nicorandil significantly reduced FBG levels and enhanced insulin tolerance in diabetic rats. In gastrocnemius and soleus muscles, Nicorandil attenuated the oxidative stress by decreasing lipid peroxidation (TBARS), increasing total glutathione and modulating GPX1‐mRNA expression in both muscle’s types. Nicorandil also increased GSH and GSH/GSSG ratio and downregulated the GCLC‐ and GSR‐mRNA in gastrocnemius, without significative effect on those enzymes’ mRNA expression in diabetic soleus muscle.
Conclusions
In diabetic rats, Nicorandil attenuates oxidative stress in slow‐ and fast‐twitch skeletal muscles by improving the glutathione system functioning. The underlying mechanisms for the modulation of glutathione redox state and the transcriptional expression of glutathione metabolism‐related genes seem to be fiber type‐dependent.
In response to diabetes mellitus, skeletal muscle is negatively affected, as is evident by reduced contractile force production, increased muscle fatigability, and increased levels of oxidative stress biomarkers. Apocynin is a widely used NADPH oxidase inhibitor, with antioxidant and anti-inflammatory potential. It has been effective for amelioration of a variety of disorders, including diabetic complications. Therefore, the present study was conducted to evaluate the effects and action mechanisms of apocynin in slow- and fast-twitch diabetic rat muscles. Male Wistar rats were rendered diabetic by applying intraperitoneally a single dose of streptozotocin (45 mg/kg). Apocynin treatment (3 mg/kg/day) was administered over 8 weeks. Fasting blood glucose (FBG), insulin tolerance and body weight gain were measured. Both slow (soleus) and fast (extensor digitorum longus, EDL) skeletal muscles were used for muscle function evaluation, oxidative stress markers, and evaluating gene expression using qRT-PCR. Treatment with apocynin significantly reduced FBG levels and enhanced insulin tolerance. Apocynin also prevented muscle contractile dysfunction in EDL muscle but had no significant effect on this parameter in soleus muscles. However, in both types of muscles, apocynin mitigated the oxidative stress by decreasing ROS levels and increasing total glutathione levels and redox state. Concomitantly, apocynin also statistically enhanced Nrf-2 and GLU4 mRNA expression and downregulated NOX2, NOX4, and NF-κB mRNA. Collectively, apocynin exhibits properties myoprotective in diabetic animals. These findings indicate that apocynin predominantly acts as an antioxidant in fast-twitch and slow-twitch muscles but has differential impact on contractile function.
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