Effect Of Iron And Diazoxide On Muscle Strength Development, Oxidative Stress And Lipid Profile In Diabetic Rats
Authors: Vargas Manuel Alejandro Vargas , Barroso Mariana Alejandro Gómez , Montes Donovan Alejandro Peña , Rojo Christian Alejandro Cortés , Molina Alfredo Alejandro Saavedra , Trujillo Xóchitl Ángelica Rosío Trujillo , Viera Miguel Ángelica Rosío Huerta , Pérez Rocío Alejandro Montoya 
Published: April 2020

Diabetes is a global health problem. Oxidative stress plays an essential role in the development of complications, among the most frequent symptoms is muscle fatigue. Diabetes also contributes to a high cardiovascular risk attributed to dyslipidemia. Diazoxide (dzx) is a drug that acts on mitoKATP. Studies indicate that this drug improves the development of muscle strength; on the other hand, it is known that iron overload (IO) increases oxidative stress, while a reduction has a protective role. The objective was to evaluate the effect of iron and dzx on the development of muscle strength, oxidative stress, and lipid profile in diabetic rats. Male Wistar rats (250g) were used in eight groups: control, diabetics, IO, diabetic + IO, low iron, diabetic + low iron, dzx, diabetic + dzx. Soleus muscle and extensor digitorum longus (EDL) of an extremity were extracted to perform the muscle tension tests, and the other limb was used to obtain homogenates to measure lipid oxidation, glutathione levels and total reactive oxygen species (ROS). Finally, the serum was collected to measure lipid profile. Rats fed with a low iron diet and dzx administration improved muscle strength and fatigue took longer to appear. The groups fed with IO had reduced muscle strength development. Regarding the lipid peroxidation, the groups of diabetic rats fed with a low iron diet (0.34 nM/mg of protein) and dzx administration (0.033 nM/mg of protein) had the lower levels of lipid peroxidation. As for the glutathione levels, diabetic rats treated with dzx obtained the highest levels of reduced glutathione (1.65 μmol of GSH/mg of protein) and oxidized glutathione (GSSG) levels in diabetic rats with a low iron diet obtained the lowest values (0.82 μmol of GSH/mg of protein). Concerning total ROS levels, diabetic rats treated with dzx got the lowest levels (2.80 DCF*mg of protein). As for the lipid profile, diabetic rats treated with dzx obtained lower levels (ẋ =105 mg/dL). Very low‐density lipoprotein (VLDL) levels were high in the group of diabetic rats without treatment (ẋ=58.06 mg/dL), and the group of diabetics + dzx obtained similar levels to the control group (ẋ=21.1 mg/dL). Dzx acts as a mitoKATP opener, previous studies reported that the opening of these channels provokes a decrease in oxidative stress during fatigue and also activates the electron transport chain, which promotes a constant production of ATP, which is necessary for energy production and in this way the generation of muscular strength. On the other hand, iron plays an essential role in the formation of the hydroxyl radical, which is the most dangerous radical, this agrees with the results we obtained in the groups that had an IO. The higher levels of oxidative stress and muscular strength were lower in IO groups; however, the iron restriction had a protective effect on oxidative stress levels. Regarding the lipid profile, both dzx and low iron diets were shown to have a positive impact on the lipid profile by mechanisms that are not yet known.