Effects of melatonin on the activity of the glutathione antioxidant system and various NADPH-generating enzymes in the liver and blood of rats with type 2 diabetes mellitus

2011 ◽  
Vol 45 (7) ◽  
pp. 385-388 ◽  
Author(s):  
A. A. Agarkov ◽  
T. N. Popova ◽  
L. V. Matasova
Author(s):  
O. B. Furka

Introduction. The most important function of the liver in the body is neutralization and destruction of toxic substances. Metabolism and utilization of chemical and biological toxins are carried out by neutralizing the hepatocyte system, followed by the removal of harmful products from the body.The aim of the study – to investigate the effect of acetaminophen on the background of type 2 diabetes mellitus on the main parameters of the glutathione unit of the antioxidant system in rat liver homogenate in time dynamics.Research Methods. The experiments were carried out on white mature rats weighing 180–220 g, contained on a standard ration of the vivarium and free access to water. We conducted 2 series of experiments. In the first, toxic acetaminophen was caused by a single intraventricular injection of acetaminophen in 2 % starch solution at a dose of 1250 mg/kg body weight (1/2 LD50), in the second suspension of acetaminophen in a 2 % starch solution at a dose of 55 mg/kg, which corresponds to the highest therapeutic dose for 7 days. The non-genetic form of experimental type 2 diabetes mellitus was modeled according to the method of Islam S., Choi H. (2007) by a single intraperitoneal injection of a streptozotocin solution (“Sigma”, USA) at a body weight (200±20) g at a rate of 65 mg/kg, which diluted with citrated buffer (pH 4.5) with a preliminary (within 15 minutes) intraperitoneal administration of nicotinamide in a dose of 230 mg/kg. For the control group, rats with the same body weight were administered with a similar volume of solvent (citrate buffer pH 4.5).Results and discussion. Activation of lipid peroximation reactions is one of the fundamental biological mechanisms of damage to biostructures and the development of cellular pathology for the actions of damaging factors of various genesis, especially under the conditions of xenobiotics.Conclusion. Acetaminophen poisoning against type 2 diabetes mellitus causes a significant disruption of compensatory mechanisms, especially the state of the enzyme and non-enzyme links of the antioxidant system.


Author(s):  
K.A. Cherepanova

Objective. The aim of the paper is to analyze the impact of plant antioxidant “Dihydroquercetin Baikalsky” on the LPO-AOS system and carbohydrate-lipid metabolism in residents of Khanty-Mansiysk with type 2 diabetes mellitus. Materials and Methods. The study enrolled 132 adult residents of Khanty-Mansiysk, including 78 people with type 2 diabetes mellitus and 54 healthy subjects. The authors examined the indicators of pro- and antioxidant activity in blood samples in all the trial subjects: products of lipid peroxidation (LPO), the state of the antioxidant system (AOS), oxidative stress coefficient. Patients with type 2 diabetes mellitus (n=48) undergoing standard glucose-lowering therapy were taking 1 capsule (60 mg) of Dihydroquercetin Baikalsky post cibum daily. Statistica 10.0 and Microsoft Excel software package were used to process the results obtained. Results. It was found that 12-week dihydroquercetin intake led to a significant decrease in primary and secondary lipid peroxidation products and an increase of AOS activity, which indicated the antioxidant effect of the bioflavonoid. The authors noted a positive trend towards a decrease in the parameters of the carbohydrate-lipid profile. Conclusion. The data obtained indicate the antioxidant properties of dihydroquercetin in persons with type 2 diabetes mellitus. Keywords: northern region, lipid peroxidation, antioxidant system, carbohydrate-lipid metabolism, dihydroquercetin. Цель. Провести анализ коррекции показателей системы ПОЛ – АОС и углеводно-липидного обмена антиоксидантом растительного происхождения «Дигидрокверцетин Байкальский» у жителей г. Ханты-Мансийск, страдающих сахарным диабетом 2 типа. Материалы и методы. В исследование включены 132 взрослых жителя г. Ханты-Мансийск, в т.ч. 78 чел. с сахарным диабетом 2 типа и 54 условно здоровых добровольца. У обследуемых лиц изучены показатели про- и антиоксидантной активности в образцах крови: продукты перекисного окисления липидов (ПОЛ), состояние антиоксидантной системы (АОС), коэффициент окислительного стресса. Группа больных сахарным диабетом 2 типа (48 чел.) на фоне стандартной сахароснижающей терапии в течение 12 нед. принимала после еды по 1 капсуле (60 мг) в день антиоксиданта «Дигидрокверцетин Байкальский». Полученные результаты статистически обработаны с использованием пакета программ Statistica 10.0 и Microsoft Excel. Результаты. Установлено, что прием дигидрокверцетина в течение 12 нед. способствовал достоверному снижению содержания первичных и вторичных продуктов ПОЛ и повышению активности АОС, что свидетельствует об антиоксидантном действии данного биофлавоноида. Отмечена положительная тенденция к снижению показателей углеводно-липидного профиля. Выводы. Полученные данные указывают на антиокислительные свойства дигидрокверцетина у лиц, страдающих сахарным диабетом 2 типа. Ключевые слова: северный регион, перекисное окисление липидов, антиоксидантная система, углеводно-липидный обмен, дигидрокверцетин.


Author(s):  
I. O. Buzdugan ◽  
O. I. Fediv ◽  
S. V. Roborchuk ◽  
L. О. Voloshyna

Objective — to investigate the functional state of endothelium and methods of correction of endothelial dysfunction in patients with gastric and duodenal peptic ulcers (GPU and DPU)  in combination with hypertension (AH) and type 2 diabetes mellitus (DM2). Materials and methods. The investigation involved 100 patients, who were divided into the groups: group 1 consisted of  20 apparently healthy individuals (AHI), group 2 included  40 patients with GPU (n = 23) and DPU (n = 17) without signs of AH and DM2, group 3 involved 40 patients with GPU (n = 15) and DPU (n = 25) in combination with hypertension and DM2. The groups were sub‑divided into subgroups A and B depending on the H. pylori strains’ toxigenicity:   group A included patients with CagA+ VacA+ strains’  combination, groups  B — infected with H. pylori with a combination of strains of CagA+ or VacA+. All patients were administered the traditional antihelicobacter therapy (AHBT) (esomeprazole 20 mg twice daily + amoxicillin 1.0 g twice daily + clarithromycin 500 mg twice daily for 10 days). To increase the effectiveness of eradication therapy, 40 patients  in addition to AHBT, received a combined probiotic (Bifidobacterium bifidum, B. lactis, Enterococcusus acidophilus, L. paracasei, L. plantarum, L. rhamnosus, L. salivarius) 1 sachet twice a day for 1 month. Eradication control was monitored 4 weeks after completion of treatment. Results. The increased expression of the vascular cell adhesion molecule‑1 (VCAM‑1) and the number of desquamated endothelial cells (DEK) and improvement of the oxidant‑antioxidant system have been established. Before the treatment, in comparison with the levels in AHI,  levels of sVCAM exceeded in 5.88 times (р < 0.05), of erythrocytic malondialdehyde in 1.92 times (р < 0.05), and levels of the reduced glutathione was lower by 46.39 % (р < 0.05). The use of triple therapy improved the endothelial condition and the state of the oxidative‑antioxidant system, and additional application of probiotic promoted more effective correction of the indices of endothelial state and oxidative‑antioxidant system by means of maximal decrease of the levels of sVCAM and erythrocytic malondialdehyde and increase of the reduced glutathione levels. Conclusions. The presence of H. pylori, in particular its toxigenic strains, results in the development of endothelial disfunction in patients with GPU and DPU, combined with arterial hypertension and DM 2.  When combined with hypertension and DM2, the course of GPU and DPU is accompanied with «mutual burden» syndrome resulting in the exhaustion of the antioxidant defense system and increased indexes of the glutathione system.  


Author(s):  
O. B. Furka ◽  
I. B. Ivanusa ◽  
M. M. Mykhalkiv ◽  
I. M. Klishch

Introduction. Acetaminophen has dose-dependent effect on the liver, which is the degree of damage depends on the concentration of this drug in plasma. When administration in large quantities of acetaminophen (accidentally or with suicidal intent) centrolobular massive necrosis occurs in the liver. Diabetes is also a risk factor for cirrhosis.The aim of the study – to study the effect of acetaminophen on main indices of antioxidant system in liver homogenate and blood plasma of rats with type 2 diabetes mellitus in time dynamics.Methods of the research. We conducted two series of experiments. In the first series toxic lesion was caused by a single intragastric administration of acetaminophen suspension in 2 % starch solution to animals in a dose of 1250 mg/kg (1/2 LD50). In the second series the suspension of acetaminophen in 2 % starch solution in a dose of 55 mg/kg was given, which corresponds to the highest therapeutic dose during 7 days. Non-genetic form of experimental type 2 diabetes mellitus was modeled by single intraperitoneal administration of streptozotocin solution in doses 65 mg/kg to rats, which was diluted by citrate buffer (pH 4.5) with the previous intraperitoneal nicotinamide administration in doses of 230 mg/kg. Rats with the same body weight, which were given the same amount of solvent (citrate buffer pH 4.5), were used as the control group.Results and Discussion. The results of the experiment show that a greater toxicity in the experimental animals causes the administration of acetaminophen on the background of type 2 diabetes.Conclusion. Toxic lesion by acetaminophen in rats with type 2 diabetes mellitus is accompanied by significant violation of enzymatic components of the antioxidant system, have a compensatory nature and direct to neutralize of free radical oxidation products.


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