Published online Dec 15, 2019. doi: 10.4239/wjd.v10.i12.546
Peer-review started: July 26, 2019
First decision: August 19, 2019
Revised: October 20, 2019
Accepted: October 27, 2019
Article in press: October 27, 2019
Published online: December 15, 2019
Processing time: 143 Days and 5.2 Hours
It is known that under conditions of tissue tolerance to insulin, observed during type 2 diabetes mellitus (DM2), there is an increased production of reactive oxygen species. Moreover, the free radicals can initiate lipid peroxidation (LPO) in lipoprotein particles. The concentration of LPO products can influence the state of insulin receptors, repressing their hormone connection activity, which is expressed as a reduction of the glucose consumption by cells. It is possible that reduction in glucose concentration during administration of 10-(6-plastoquinonyl) decyltriphenylphosphonium (SkQ1) to rats with DM2 may be related to the antioxidant properties of this substance.
To establish the influence of SkQ1 on free-radical homeostasis in the heart and blood serum of rats with streptozotocin-induced hyperglycemia.
To induce hyperglycemia, rats were fed a high-fat diet for 1 mo and then administered two intra-abdominal injections of streptozotocin with a 7-d interval at a 30 mg/kg of animal weight dose with citrate buffer equal to pH 4.4. SkQ1 solution was administered intraperitoneally at a 1250 nmol/kg dose per day. Tissue samples were taken from control animals, animals with experimental hyperglycemia, rats with streptozotocin-induced glycemia that were administered SkQ1 solution, animals housed under standard vivarium conditions that were administered SkQ1, rats that were administered intraperitoneally citrate buffer equal to pH 4.4 once a week during 2 wk after 1-mo high-fat diet, and animals that were administered intraperitoneally with appropriate amount of solution without SkQ1 (98% ethanol diluted eight times with normal saline solution). To determine the intensity of free radical oxidation and total antioxidant activity, we used the biochemiluminescence method. Aconitate hydratase (AH), superoxide dismutase, and catalase activities were estimated using the Hitachi U-1900 spectrophotometer supplied with software. The amount of citrate was determined by means of the Natelson method. Real-time polymerase chain reaction was carried out using an amplifier ANK-32.
It was found that the mitochondrial-directed antioxidant elicits decrease of biochemiluminescence parameter values that increase by pathology as well as the levels of primary products of LPO, such as diene conjugates and carbonyl compounds, which indicate intensity of free radical oxidation. At the same time, the activity of AH, considered a crucial target of free radicals, which decreased during experimental hyperglycemia, increased. Apparently, increasing activity of AH influenced the speed of citrate utilization, whose concentration decreased after administering SkQ1 by pathology. Moreover, the previously applied anti-oxidant during hyperglycemia influenced the rate of antioxidant system mobilization. Thus, superoxide dismutase and catalase activity, as well as the level of gene transcript under influence of SkQ1 at pathology, were changing to the direction of control groups values.
According to the results of performed research, SkQ1 can be considered a promising addition to be included in antioxidant therapy of DM2.
Core tip: The results of this research suggest that the mitochondria targeted antioxidant 10-(6-plastoquinonyl) decyltriphenylphosphonium (SkQ1) might be a potential substance for incorporation into the antioxidant therapy of type 2 diabetes mellitus. The ability of this compound to lower the intensity of free-radical processes, acting as the key component of the pathogenesis of the type 2 diabetes mellitus, serves as the basis for this conclusion. Thus, after the introduction of SkQ1 to the animals with streptozotocin induced hyperglycemia, the values of the biochemiluminescence parameters reflecting the free-radical oxidation intensity, the concentration of diene conjugates and carbonyl products of protein oxidation, aconitate hydratase activity, and citrate content approached those of control values. At the same time, the activity level of the antioxidant enzymes superoxide dismutase and catalase approached those of normal values.