RESUMO
BACKGROUND: 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. AIM: To establish the influence of SkQ1 on free-radical homeostasis in the heart and blood serum of rats with streptozotocin-induced hyperglycemia. METHODS: 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. RESULTS: 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. CONCLUSION: According to the results of performed research, SkQ1 can be considered a promising addition to be included in antioxidant therapy of DM2.
RESUMO
Acute hepatitis results from oxidative stress triggered by hepatotoxic drugs causing liver injury and the activation of caspases cascade. The glutathione antioxidant system protects against reactive oxygen species and mitigates development of these processes. The effectiveness of silymarin, a polyphenolic flavonoid, essenthiale, composed of phosphatidyl choline, and melaxen, a melatonin-correcting drug, as hepatoprotectors has been investigated. The variation of 6-sulfatoxymelatonin (aMT6s), resulting from the biotransformation of melatonin, and GSH has been measured. The activities of caspase-1 and caspase-3, glutathione antioxidant system, and NADPH-generating enzymes were determined. The aMT6s decreases in patients with drug hepatitis and recovers with administration of mexalen. GSH increased in the presence of the studied hepatoprotectors. Pathologically activated caspase-1 and caspase-3 decreased their activities in the presence of hepatoprotectors with melaxen showing the highest effect. The positive effect of melatonin appears to be related to the suppression of decompensation of the glutathione antioxidant system functions, recovery of liver redox status, and the attenuation of inhibition of the NADPH supply.
RESUMO
Correlation between intensity of free radical processes estimated by biochemiluminesce parameters, content of lipoperoxidation products, and changes of glutathione peroxidase (GP, EC 1.11.1.9) and glutathione reductase (GR, EC 1.6.4.2) activities at rats liver injury, after 12, 36, 70, 96, 110, and 125 hours & tetrachloromethane administration have been investigated. The histological examination of the liver sections of rats showed that prominent hepatocytes with marked vacuolisation and inflammatory cells which were arranged around the necrotic tissue are more at 96 h after exposure to CCl4. Moreover maximum increase in GR and GP activities, 2.1 and 2.5 times, respectively, was observed at 96 h after exposure to CCl4, what coincided with the maximum of free radical oxidation processes. Using a combination of reverse transcription and real-time polymerase chain reaction, expression of the glutathione peroxidase and glutathione reductase genes (Gpx1 and Gsr) was analyzed by the determination of their respective mRNAs in the rat liver tissue under toxic hepatitis conditions. The analyses of Gpx1 and Gsr expression revealed that the transcript levels increased in 2.5- and 3.0-folds, respectively. Western blot analysis revealed that the amounts of hepatic Gpx1 and Gsr proteins increased considerably after CCl4 administration. It can be proposed that the overexpression of these enzymes could be a mechanism of enhancement of hepatocytes tolerance to oxidative stress.
