الفهرس 
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Abstract
Skeletal muscle atrophy or wasting represents an important problem. Muscle atrophy may result from disuse and metabolic disease. It has been recently recognized that skeletal muscle is an endocrine organ that can express, synthesize and secrete a variety of bioactive molecules which exert significant regulatory effects. These bioactive molecules include; myostatin,interleukin-6 and hydrogen sulfide (H2S). Recently, H2S is proved to be important in a broad range of physiological and pathophysiological functions. H2S travels freely across cell membranes activating various molecular targets such as activation of KATP channels. Thus, we aimed in this work to: investigate the possible effect of H2S on skeletal muscle in cast immobilization model of hindlimbs in rats. Also, to clarify the role of ATP sensitive K channels in the mechanism of action of H2S on skeletal muscle. This study was conducted on 40 adult male albino rats aged 6-8 weeks, weighing 180-250 grams. Animals were bred and housed in the animal house of Medical Experimental Research center (MERC). Rats were divided randomly into 4 groups (10 rats each): group (I) (Immobilized group) (I group): with their left hindlimbs were immobilized by plaster cast. group (II) (Immobilized and H2S group) (IH group): in which they were injected intraperitoneally by sodium hydrosulfide (NAHS) at a dose of 2mg/kg daily combined with immobilization. group (III) (Immobilized with combined H2S and ATP sensitive K channels blocker group) (IHG group): in which they received glibenclamide (sensitive KATP channels blocker) at a dose of 5 mg/kg daily by gastric gavage combined with sodium hydrosulfide (NAHS) and immobilization. All the three groups were maintained with plaster cast for two weeks. The contralateral loose limb were used as a control for each group and to ensure that the contralateral hindlimb were an adequate control reference, a group of negative control rats that not immobilized, not receiving any drugs were used group (IV) (negative control group) (C group). At the end of the 2 weeks, the rats were anesthetized with thiopental injected intraperitoneally. Rats were sacrificed by cardiac puncture. Then, casts in immobilized groups were removed to obtain our preparations by isolation of soleus and tibialis anterior muscles from immobilized and contralateral limbs in order to record the contractile parameters by computerized data acquisition system unit MP45(BIOPAC Student Lab 3.7.3.). Then, these tissue samples were used for biochemical and histopathological examination. The present work revealed that: 1.The immobilized group (I gp) showed significant reduction in the relative muscle weight ratio, significant deterioration in the contractile parameters, significant increase in the tissue levels of malondialdehyde, significant reduction in total antioxidant capacity in the muscle together with significant atrophic changes in both soleus and tibialis anterior muscles as detected by histopathological examination. These atrophic changes were in form of marked separation of the muscle fibers, marked increased fibrous tissue and severe infiltration by inflammatory cells. 2. NAHS supplementation in (IH gp) can help in protection against myopathy as it showed significant increase in relative muscle weight ratio, significant improvement in the contractile parameters with reduction of fatigue index and better recovery. Also, it showed significant decrease in MDA with significant enhancement in TAC levels and significant alleviation of atrophic changes in both soleus and tibialis anterior muscles. This protective effect may due to anti-apoptotic, anti-inflammatory, vasorelaxant, antioxidant and angiogenic action of hydrogen sulfide. 3. Addition of glibenclamide to NAHS treatment to immobilized rats (IHG gp) led to similar changes in soleus and tibialis anterior muscles as the immobilized group. So that, glibenclamide can be assumed to abolish the protective effect of hydrogen sulfide most probably through blocking KATP channels. Conclusion from the results showed in this work, it is possible to conclude that H2S has a protective role in the cast immobilization rat model of myopathy and it exerts its actions mainly through opening the ATP sensitive K+ channels. Recommendations Hydrogen sulfide donors can be used as additional dietary supplementations for the prevention of myopathy in prolonged cast immobilization. Also, it can be used in diabetic patients as administration of glibenclamide as an anti-diabetic drug resulted in myopathy. In addition, we can recommend replacement of glibenclamide as antidiabetic drug with other sulfonylurea drugs as glimepiride as it causes less myopathy.