The effects of dpp4 inhibitors on lipid status and blood pressure in rats with diabetes mellitus type 2

© 2019, University of Kragujevac, Faculty of Science. All rights reserved. The aim of the present study was to examine, evaluate and compare the effects of administered dipeptidyl peptidase-4 (DPP4) inhibitors saxagliptin and sitagliptin on lipid status parameters and blood pressure in rats with streptozotocine induced diabetes mellitus type 2. Forty-eight Wistar albino rats were divided randomly into 4 groups: 1. group I: control healthy group; 2. group II: rats with diabetes mellitus type 2; 3. group III: rats with diabetes mellitus type 2+ treated with 0.6 mg/kg of sitagliptin; 4. group IV: rats with diabetes mellitus type 2 treated with 0.45 mg/kg of saxagliptin. The rats from experimental groups were fed with a high-fat diet for 4 weeks and after 6–8 h of starvation received one dose of streptozotocin (STZ) intraperitoneally (25 mg/kg body weight) to induce type 2 diabetes mellitus (T2DM). Animals with fasting glucose above 7 mmol/L and insulin over 6 mmol/L were included in the study as rats with T2DM. Upon completion of the experiments, the blood was collected from the anesthetized animals and serum triglyceride (TG), total cholesterol (TCH), high density lipoprotein (HDL), and low density lipoprotein (LDL) were measured using spectrophotometry and commercial kits. At the beginning of the study and the day before sacrificing animals, the blood pressure and heart rate were measured by a tail-cuff noninvasive method. DPP4 inhibitors, as glucagon-like peptide-1 (GLP-1) agonists, were associated with modest reductions in DBP, LDL-C, TCH, and TGL and significant improvement in HDL, SBP and HR

The effect of the chronic administration of dpp4inhibitors on systemic oxidative stress in rats with diabetes type 2

© 2019, University of Kragujevac, Faculty of Science. All rights reserved. Type 2 diabetes (T2DM) is characterized by well-preserved insulin secretion; however, the surrounding tissue is insensitive to insulin, resulting in increased blood glucose level due to the inability of tissues to convert glucose into energy. As a result of chronic non-regulation of glucose levels and high daily fluctuations in the blood, the micro-and macrovascular complications occur in these patients. Complications develop through two main mechanisms: induction of oxidative stress and innate immunity. In this regard, the aim of this study was to examine the effect of four week administration of DPP4 inhibitors (saxagliptin, sitagliptin and vildagliptin) to the parameters of oxidative stress and antioxidant defense in the group of rats with diabetes type 2 (T2DM). Sixty Wistar albino rats were divided randomly into 5 groups: group I: control healthy group; group II: rats with diabetes type 2; group III: rats with diabetes type 2 treated with 0.6 mg/kg of sitagliptin; group IV: rats with diabetes type 2 treated with 0.45 mg/kg of saxagliptin, group V: rats with diabetes type 2 treated with 9 mg/kg vildagliptin. The rats from experimental groups were fed with a high-fat diet for 4 weeks and after 6–8 h of starvation received one dose of streptozotocin (STZ) intraperitoneally (25 mg/kg body weight) to induce T2DM. Animals with fasting glucose above 7 mmol / L and insulin over 6 mmol / L were included in the study as rats with T2DM. Upon completion of the experiments, the blood was collected from the anesthetized animals and used for sphectrophotometrical determination of parameters of oxidative stress, and antioxidative defense. T2DM induced significant increase in production of reacitve oxygen species (ROS) (superoxide anion radical and hydrogen peroxide), but additional four-week administration of gliptins induced decrease in ROS values. On the other hand, T2DM induced decrease of nitric oxide, superoxide dismutase, catalaze, and reduced gluthation and concomitant therapy with gliptins induced increase of these parametars, suggesting significant antioxidant potential of this group of drugs

The influence of Vitamin E-coated dialysis membrane on oxidative stress during a single session of on-line hemodiafiltration

Background/Aim. Oxidative stress is an important risk factor for the development of cardiovascular atherosclerotic diseases in the population of patients treated with regular hemodialysis. Bioincompatibility of the dialysis membrane and increased concentration of endotoxin in the hemodialysis solution are two main factors that can trigger oxidative stress. This paper was intended to examine the effect of a vitamin E-coated membrane on oxidative stress during a single session of on-line hemodiafiltration. Methods. Twenty-four patients undergoing hemodiafiltration with vitamin E-coated polysulfone dialysis membrane (Leoceed 21H) were examined, followed by a polysulfone dialysis membrane treatment without vitamin E (FX800). The following parameters of oxidative stress were measured: superoxide anion radical (O2-), hydrogen peroxide (H2O2), thiobarbutyric acid reactive substances (TBARS), nitric oxide (NO2-), catalase (CAT), superoxide dizmutase (SOD), and reduced glutathione (GSH) activity. Statistical analysis included the Kolmogorov-Smirnov test, Student-t test and Wilcoxon test. Results. On-line hemodiafiltration using a high-flux polysulfone vitamin E-coated membrane led to significant reduction of TBARS concentration and SOD activity, while the on-line hemodiafiltration session using a high-flux polysulfone membrane that is not vitamin E-coated induced a significant increase in H2O2 concentration in the serum and a decrease in SOD activity. There was no statistical significance among the other parameters of oxidative stress. Conclusion. A single session of on-line hemodiafiltration using a vitamin E-coated polysulfone membrane significantly affects oxidative stress. After a single session of online hemodiafiltration using a vitamin E-coated membrane, the concentration of TBARS has significantly decreased. The decreased activity of superoxide dismutase could be a consequence of an increased loss of microelements during an on-line hemodiafiltration session using a high-flux polysulfone membrane. Patient selection, continuous on-line hemodiafiltration using a vitamin E-coated polysulfone membrane over a 3-6 month period and increased antioxidant protection capacity could possibly reduce the risk of cardiovascular morbidity and mortality in patients treated by hemodialysis

The Influence of Menopause and Inflammation on Redox Status and Bone Mineral Density in Patients with Rheumatoid Arthritis

© 2021 Aleksandra Stojanovic et al. Although oxidative stress is considered to be one of the key pathogenic factors in rheumatoid arthritis (RA), there is insufficient knowledge regarding the impact of menopause on redox status in this population. Thus, this study is aimed at assessing the influence of menopause within healthy women and within RA patients as well as the impact of RA in premenopausal and postmenopausal women on redox status, with special reference to bone mineral density (BMD). A total of 90 women were included in the study, 42 with RA and 48 age-matched healthy controls. They were divided into subgroups according to the presence of menopause. Following oxidative stress parameters were measured spectrophotometrically: index of lipid peroxidation (measured as TBARS), nitrites (NO2-), superoxide anion radical (O2-), hydrogen peroxide (H2O2), superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH). BMD was assessed by using a dual-energy X-ray absorptiometry scanner. Comorbidities and drug history were recorded. The levels of H2O2 and TBARS were elevated in patients with RA, while NO2- and O2- increased in healthy women, both in premenopausal and postmenopausal groups. SOD activity decreased in postmenopausal RA patients. BMD was reduced in postmenopausal RA women. There was a correlation between NO2- and O2- with Health Assessment Questionnaire (HAQ) index in RA patients. Given that postmenopausal state was associated with elevated oxidative stress within healthy women and that menopausal state did not affect redox homeostasis within RA patients, but the redox homeostasis was altered in both RA groups compared to healthy women, it can be presumed that impaired redox status in RA occurred due to presence of the disease, irrespective of age. Moreover, menopause attenuates BMD reduction in women with RA. These results may indicate the need for therapeutic use of antioxidants in the form of supplements in women with RA, regardless of age

Anti-inflammatory and Antioxidant Effects of Melissa officinalis Extracts: A Comparative Study

Melissa officinalis L. (MO), traditionally referred to as lemon balm, is one of the lemon-scent aromatic herbs widely used in traditional medicine due to its calming, sedative, and anti-arrhythmic effects. Furthermore, several studies have linked its therapeutic potential with its antioxidant properties. Here, we aimed to evaluate and compare the content of active components, antioxidant, and anti-inflammatory potential of three different MO extracts (MOEs), ethanolic macerate (E1), aqueous (E2), and ethanolic (E3), obtained under reflux and their effects on systemic redox status after acute per os administration in vivo post-carrageenan application. The HPLC analysis revealed that the most abundant constituent in all the three extracts was rosmarinic acid (RA), with higher content in E1 and E3 than in E2 (P < 0.05). The highest flavonoid content was found in the aqueous extract, especially quercetin (P < 0.05). For the carrageenan-induced paw edema model, dark agouti rats were used and divided into the groups: Control, indomethacin, E1, E2, and E3 subgrouped according to applied doses: 50, 100, and 200 mg/kg. Ethanolic macerate (E1200) and aqueous (E2100) MOE were shown to be anti-inflammatory agents in the carrageenan paw edema model, with the most prominent edema inhibition in the sixth hour post-carrageenan (63.89% and 69.44%, respectively, vs. 76.67% in the indomethacin group). All the three extracts reduced the production of pro-oxidants H2O2 and TBARS post-carrageenan and increased GSH levels compared to control (P < 0.05). These data imply the possible future usage of MOEs to prevent inflammatory and oxidative stress-related diseases

Melissa officinalis L. as a Nutritional Strategy for Cardioprotection

This review aimed to provide a summary on the traditional uses, phytochemistry, and pharmacological activities in the cardiovascular system and cardiotoxicity of Melissa officinalis (MO), with the special emphasis on the protective mechanisms in different cardiovascular pathologies. MO is a perennial aromatic herb commonly known as lemon balm, honey balm, or bee balm, which belongs to Lamiaceae family. Active components are mainly located in the leaves or essential oil and include volatile compounds, terpenoid (monoterpenes, sesquiterpenes, triterpenes), and polyphenolic compounds [rosmarinic acid (RA), caffeic acid, protocatechuic acid, quercitrin, rhamnocitrin, luteolin]. For centuries, MO has been traditionally used as a remedy for memory, cognition, anxiety, depression, and heart palpitations. Up until now, several beneficial cardiovascular effects of MO, in the form of extracts (aqueous, alcoholic, and hydroalcoholic), essential oil, and isolated compounds, have been confirmed in preclinical animal studies, such as antiarrhythmogenic, negative chronotropic and dromotropic, hypotensive, vasorelaxant, and infarct size–reducing effects. Nonetheless, MO effects on heart palpitations are the only ones confirmed in human subjects. The main mechanisms proposed for the cardiovascular effects of this plant are antioxidant free radical–scavenging properties of MO polyphenols, amelioration of oxidative stress, anti-inflammatory effects, activation of M2 and antagonism of β1 receptors in the heart, blockage of voltage-dependent Ca2+ channels, stimulation of endothelial nitric oxide synthesis, prevention of fibrotic changes, etc. Additionally, the main active ingredient of MO-RA, per se, has shown substantial cardiovascular effects. Because of the vastness of encouraging data from animal studies, this plant, as well as the main ingredient RA, should be considered and investigated further as a tool for cardioprotection and adjuvant therapy in patients suffering from cardiovascular diseases

Formulation and evaluation of helichrysum italicum essential oil-based topical formulations for wound healing in diabetic rats

As proper wound management is crucial to reducing morbidity and improving quality of life, this study evaluated for the first time the wound healing potential of H. italicum essential oil (HIEO) prepared in the form of ointment and gel in streptozotocin-induced diabetic wound models in rats. After creating full-thickness cutaneous wounds, forty-eight diabetic rats were divided into six groups: (1) negative control; (2) positive control; (3) ointment base; (4) gel base; (5) 0.5% HIEO ointment (6) 0.5% HIEO gel. Wound healing potential was determined by the percentage of wound contraction, hydroxyproline content, redox status, and histological observation. A significant decrease in the wound size was observed in animals treated with HIEO formulations compared with other groups. The HIEO groups also showed a higher level of total hydroxyproline content, and more pronounced restitution of adnexal structures with only the underlying muscle defect indicating the incision site. Hence, our results legitimate the traditional data of the pro-healing effect of HIEO because HIEO in both formulations such as gel and ointment exhibited the significant wound repairing effect in the incision wound model

Protective Role of Vitamin B<inf>1</inf> in Doxorubicin-Induced Cardiotoxicity in Rats: Focus on Hemodynamic, Redox, and Apoptotic Markers in Heart

Up until now, the specific mechanisms involved in doxorubicin (DOX)-induced cardiotoxicity have not been fully elucidated. Since thiamine deficiency is associated with myocardial dysfunction and it may lead to cardiomyopathy, we aimed to investigate whether thiamine (Vitamin B1) treatment provides cardioprotection and modulates DOX mediated subchronic cardiotoxicity as well as to determine possible mechanisms of its effects. The study involved 48 Wistar albino rats divided into four groups: healthy non-treated rats and healthy rats treated with thiamine and DOX rats without treatment and DOX rats treated with thiamine. DOX was applied as a single i.p.injection (15mg/kg), while thiamine treatment lasted 7days (25mg/kg/dayi.p.). Before and after the treatment hemodynamic changes were monitored in vivo by echocardiography. When the protocol was completed, animals were sacrificed and rat hearts were isolated in order to evaluate parameters of cardiac oxidative stress [superoxide anion radical-O2−, hydrogen peroxide-H2O2, nitric oxide-NO−, index of lipid peroxidation-thiobarbituric acid (TBA) reactive substances (TBARS), superoxide dismutase – SOD, catalase (CAT), and reduced glutathione-GSH] and apoptosis (Bax, Bcl-2, caspases). DOX treatment significantly reduced the ejection fraction, while thiamine treatment led to its minor increase in the DOX-treated group. In that sense, heart oxidative stress markers were significantly increased in DOX-treated rats, while therapeutic dose of thiamine decreased the levels of free radicals. Our study demonstrated the promising ameliorative effects of thiamine against DOX-induced cardiotoxicity through modulation of oxidative stress, suppression of apoptosis, and possibility to improve myocardial performance and morphometric structure of rats` hearts