Nicorandil improves post-fatigue tension in slow skeletal muscle fibers by modulating glutathione redox state

Abstract

Fatigue is a phenomenon in which force reduction has been linked to impairment of several biochemical processes. In skeletal muscle, the ATP-sensitive potassium channels (K) are actively involved in myoprotection against metabolic stress. They are present in sarcolemma and mitochondria (mitoK channels). K channel openers like nicorandil has been recognized for their ability to protect skeletal muscle from ischemia-reperfusion injury, however, the effects of nicorandil on fatigue in slow skeletal muscle fibers has not been explored, being the aim of this study. Nicorandil (10 μM), improved the muscle function reversing fatigue as increased post-fatigue tension in the peak and total tension significantly with respect to the fatigued condition. However, this beneficial effect was prevented by the mitoK channel blocker 5-hydroxydecanoate (5-HD, 500 μM) and by the free radical scavenger N-2-mercaptopropionyl glycine (MPG, 1 mM), but not by the nitric oxide (NO) synthase inhibitor Nω-nitro-L-arginine methyl ester (L-NAME, 100 μM). Nicorandil also decreased lipid peroxidation and maintained both reduced glutathione (GSH) levels and an elevated GSH/GSSG ratio, whereas total glutathione (TGSH) remained unaltered during post-fatigue tension. In addition, NO production, measured through nitrite concentrations was significantly increased with nicorandil during post-fatigue tension; this increase remained unaltered in the presence of nicorandil plus L-NAME, nonetheless, this effect was reversed with nicorandil plus MPG. Hence, these results suggest that nicorandil improves the muscle function reversing fatigue in slow skeletal muscle fibers of chicken through its effects not only as a mitoK channel opener but also as NO donor and as an antioxidant.

Nicorandil decreases oxidative stress in slow‐ and fast‐twitch muscle fibers of diabetic rats by improving the glutathione system functioning

“…An assay of thiobarbituric acid reactive substances (TBARS) was used as a marker of lipid peroxidation in soleus and gastrocnemius muscles according to the method described by our group 23 .…”

“…Nicorandil has been recognized to have clinical significance 16 . Researchers have reported effects of nicorandil on cardiovascular diseases, protecting against ischemia-reperfusion injury in heart [17][18][19][20] , and in skeletal muscle [21][22][23] . Nicorandil has an action linked with its functions as K ATP channel opener 17,24,25 , nitric oxide donor activity 18,19 , and cell antioxidant capacity enhancer [26][27][28] .…”

“…Nicorandil has an action linked with its functions as K ATP channel opener 17,24,25 , nitric oxide donor activity 18,19 , and cell antioxidant capacity enhancer [26][27][28] . We have recently reported that Nicorandil improves muscle function by reversing fatigue and modulating glutathione redox state in slow chicken skeletal muscle fibers 23 . Likewise, in STZ-induced diabetic rats, Nicorandil protects, via a radical scavenging effect, islet b-cells against damage induced by STZ, both in vivo and in vitro 29 .…”

Role of Adenosine Triphosphate Sensitive Potassium Channels in Glucocorticoid Induced Myopathy of a Rat Model

“…Also, glibenclamide was claimed to affect the muscle IGF-1 expression and muscle protein content (12). Nicorandil was chosen as a channel opener due to its hyperkalemic effect, its effect on skeletal muscle contractility, its claimed relation to IGF-1 expression, and the claim of being a myopathic drug (22)(23)(24).…”

N-(2-mercaptopropionyl)-glycine enhances in vitro pig embryo production and reduces oxidative stress

“…Different studies 15 – 17 have demonstrated the capacity of NMPG to reduce the deleterious effects of ROS in injuries caused by cardiac ischemia. This product has also been used in vitro to counteract high oxidative stress conditions in rat pheochromocytoma (PC12) cells 18 , skeletal muscle fibers 19 and human prostate cancer cells 20 .…”