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Given the heightened risk of diabetes‐related cardiovascular events associated with inactivity, this study investigates the molecular mechanisms of vascular damage in streptozotocin (STZ)‐induced diabetic rats. The aim is to elucidate the impact of different exercises (interval and continuous training) and metformin on biochemical parameters, aortic injury, oxidative stress, and inflammation to provide insights into potential therapeutic interventions for diabetes‐associated vascular complications. Male Wistar rats were administered a single dose of STZ (60 mg/kg) to induce diabetes. Diabetic rats underwent either interval training or continuous training (40 min/day, 5 days/week, 6 weeks), received metformin (300 mg/kg), or a combination of metformin and exercise. After 6 weeks, biochemical parameters in serum and oxidative stress markers and mRNA expression of endothelial nitric oxide synthase (eNOS), lectin‐like oxidized low‐density lipoprotein receptor‐1 (LOX‐1), and intercellular adhesion molecule‐1 (ICAM‐1) in aorta tissue were assessed. Serum levels of fasting blood sugar (FBS), triglyceride (TG), total cholesterol (TC), low‐density lipoprotein (LDL), TG/HDL, TC/HDL, and LDL/HDL ratios were significantly reduced in all treatment groups compared to the diabetes group. Both types of exercises, metformin, and exercise+metformin combinations, significantly reduced oxidative stress by decreasing malondialdehyde (MDA) and enhancing the antioxidant status in the aortic tissue compared to the diabetic group. In addition, in exercise groups, metformin, and combination groups, the expression of eNOS was significantly elevated, while LOX‐1 and ICAM‐1 expression significantly decreased compared to the diabetic group. In most cases, the combination of exercise and metformin (especially interval training) was more effective than exercise alone. It seems that exercise along with taking metformin can be considered as a therapeutic method by improving hyperglycemia and hyperlipidemia and reducing oxidative stress and vascular inflammatory responses, leading to ameliorating biomarkers function related to endothelial damage in experimental diabetes conditions. [ABSTRACT FROM AUTHOR]

Background: Exercise training could be essential in preventing pathological cardiac remodeling in diabetes. Therefore, the effects of moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT) singly or plus metformin on diabetes-induced cardiomyopathy were investigated in this study. Methods: Forty-nine Wistar rats (male) were recruited. Seven groups of animals were treated for six weeks as control, diabetes, MICT (15 m/min, 40 min/day), HIIT (20 m/min, 40 min/day), metformin (300 mg/kg), HIIT+metformin (Met-HIIT), and MICT+metformin (Met-MICT). The metformin was orally administered with an intragastrical needle, and the exercised rats were trained (5 days/week) with a motorized treadmill. Metabolic parameters, echocardiographic indices, histopathology evaluation, and assessment of gene expression connected with cardiac fibrosis, hypertrophy, mitochondrial performance, and intracellular calcium homeostasis were investigated. Results: Our results demonstrated that all the interventions prevented weight loss and enhanced heart weight/body weight ratio and fasting plasma glucose in diabetic rats. Both types of exercise and their metformin combinations improved diabetic animals' echocardiography indices by enhancing heart rate, fractional shortening (FS), ejection fraction (EF) and reducing end-systolic and end-diastolic diameter of left ventricular (LVESD and LVEDD). Gene expression of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), transforming growth factor (TGF)-ß, and collagen increased in the diabetes group. In contrast, the gene expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1a), AMP-activated protein kinase (AMPK), ryanodine receptors (RyR), and Ca2+ ATPase pump of the sarcoplasmic reticulum (SERCA) was reduced in diabetic animals. Exercise training alone or in combination with metformin reversed these changes. Moreover, diabetes-induced cardiac fibrosis was ameliorated in treated groups. All indicators of diabetic cardiomyopathy were improved more in the Met-HIIT group than in other groups. Conclusions: Exercise training, notably with metformin combination, alleviated diabetes-induced cardiac complications. The beneficial effects of exercise could be related to improving pathological cardiac remodeling and enhancing cardiac function. [ABSTRACT FROM AUTHOR]

Many diabetes-related complications are caused by oxidative stress. In the current study, the protective effect of Cinnamomum cassia against diabetes-induced liver and kidney oxidative stress was evaluated. The male Wistar rats (n=48) were randomly divided into six groups including; control group received 500 µL normal saline orally for 42 days. Diabetes groups received intraperitoneally (i.p.) streptozotocin (STZ) as single-dose (60 mg/kg, i.p.). Cinnamon extract (100, 200, 400 mg/kg) and metformin (300 mg/kg) were orally administered to diabetic rats for 42 days. After the experiment period, the animals were anesthetized and the liver and kidney tissues were quickly removed and restored for oxidative stress evaluation. The levels of malondialdehyde (MDA), total thiol content, glutathione (GSH), nitric oxide (NO) metabolites, as well as, superoxide dismutase (SOD) and catalase (CAT) activities were measured in kidney and liver tissue. The level of MDA, SOD, and CAT activities increased significantly, while the total thiol content, and NO production were significantly reduced in diabetic animals compared to the control group (from p<0.05 to p<0.001). Treatment with cinnamon extract significantly decreased the MDA level, as well as, SOD and CAT activities in the liver and kidney of diabetic rats (from p<0.05 to p<0.001). In the liver and kidney of cinnamon treated groups, GSH and total thiol contents and NO production were significantly higher than diabetic group (from p<0.05 to p<0.001). Cinnamon extract due to its potent antioxidant property could be effective in decrease of diabetes-induced oxidative stress that plays a major role in renal and hepatic complications. [ABSTRACT FROM AUTHOR]

The present study compared the effects of Portulaca oleracea (P. oleracea) seed hydro-alcoholic extract, valsartan, and vitamin E on hemodynamic changes, oxidative stress markers and cardiac hypertrophy in a model of thyrotoxicosis. The hyperthyroid state was induced by intraperitoneal injection of levothyroxine (100 µg/kg) for 4 weeks in male adult rats. After 2 weeks, vitamin E (20 mg/kg), valsartan (8 mg/kg), and P. oleracea seed extract (400 mg/kg) were administered in three groups of thyrotoxic rats. The control group was given a daily injection of normal saline. Systolic blood pressure and heart rate were measured on three occasions with tail cuff. At the end of the fourth week, the animals were scarified and serum samples and heart tissue were collected for biochemical and histological studies. The levothyroxine increased heart rate and systolic blood pressure. A lower heart rate and reduced systolic blood pressure were observed in groups receiving valsartan and P. oleracea extract. The heart weight/body weight ratio increased in groups treated with levothyroxine, but in a microscopic study, cardiomyocyte width was not different between the groups. Levothyroxine increased the level of malondyaldehide and NO metabolite but reduced the thiol concentration, superoxide dismutase, and catalase activities. However, treatment with vitamin E and P. oleracea extract increased the thiol concentration, superoxide dismutase and catalase activities while decreasing malondyaldehide level. In addition, treatment with P. oleracea extract and valsartan decreased NO metabolite level. Treatment with P. oleracea extract improved levothyroxine induced oxidative stress and hemodynamic changes. These effects may be for antioxidant components. [ABSTRACT FROM AUTHOR]

Objective: Apium graveolens L. (celery) seed has been used for hypertension treatment. To provide a pharmacological basis, the vasorelaxant effect of celery seed extract was investigated in isolated rat aorta. Materials and Methods: Wistar male rats (200-250 g) were divided into 15 groups (n=7 for each group). The vasorelaxant response of different concentrations of celery seed extract (0.05, 0.1, 0.25, 0.5, 1, and 2 mg/ml) on isolated aorta precontracted with phenylephrine (PE) or KCl was evaluated by organ bath technique. The role of endothelium, extracellular calcium influx, intracellular sources of calcium, and potassium channels in vasorelaxant effect of celery seed extract was investigated. Results: The extract showed a concentration-dependent relaxation in the isolated aorta contracted with PE and KCl that was endothelium-dependent at lower concentrations. Pretreatment of aortic rings with indomethacin or L-NAME, did not affect the vasorelaxation induced by celery seed extract. The extract inhibited KCl and PE-induced contractions in cumulative calcium concentrations as well as after incubation with diltiazem in denuded aortic rings of endothelium. The relaxation induced by celery seed extract was inhibited by 4-aminopyridine. Conclusion: This relaxation was mediated by inhibiting calcium influx into vascular smooth muscle cells. Also, voltage-dependent potassium channels were involved in inducing the vasorelaxant effect of celery seed extract. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is a common metabolic disease with considerable morbidity and mortality. Untreated or improperly-treated diabetes can be associated with several long-term complications that necessitate an effective way to manage diabetes. Due to the side effects of synthetic glucose-lowering agents, alternative therapeutic modalities such as medicinal plants have attracted notable attention. Teucrium polium L. is a medicinal herb with antioxidant, antinociceptive, anti-inflammatory, hypolipidemic, hepatoprotective, and hypoglycemic properties. In vitro and in vivo studies have been conducted to characterize the anti-diabetic properties of Teucrium polium L. and its bioactive compounds. We conducted a literature study using Scopus, PubMed, and Google Scholar including the keywords "diabetes" and "Teucrium polium". We also scanned all the references cited by the retrieved articles. According to this review, Teucrium polium administration displayed anti-diabetic effects by targeting different mechanisms and pathways, such as enhancement of insulin secretion and insulin level, improvement of oxidative damage, regeneration of pancreatic β-cells, and promotion of glucose uptake in muscle tissues by increasing GLUT-4 translocation as well as inhibiting α-amylase activity. Although Teucrium polium has been widely regarded as a traditional method, the pharmacological studies on anti-diabetic effects are not sufficient, most studies are either in-vivo or in-vitro. The preclinical and clinical studies are further required to confirm the efficacy of Teucrium polium. [ABSTRACT FROM AUTHOR]

Background: Although numerous studies have proven that estrogen (Est) has a protective effect on the development of hypertension, more research needs to be done to show its detailed mechanism in a variety of hypertension. The important role of active oxygen species in blood pressure is well defined. We examined whether or not sex hormones change the growth of reactive oxygen species (ROS) ‎in kidneys after central microinjection of angiotensin II (Ang II).‎ Materials and methods: Female Wistar rats, 8 weeks old (200 ± 10 g) were used in this study. The animal groups were (1) Sham, (2) Ovariectomy (OVX), (3) Sham-Hypertension (Sham-Hyper), (4) OVX-Hypertension (OVX-Hyper), (5) Sham-Hyper-Est, (6) OVX-Hyper-Est‎;‎ (7) Sham-Hyper-Testosterone (Tst) and (8) OVX-Hyper-Tst. Solutions of 1% NaCl and 0.1 KCl ‎were used and desoxycorticostrone (doca-salt) was injected (45 mg/kg) 3 times a week in Hypertension groups. Estradiol and Tst (2 mg/kg and ‎5 mg/kg‎; daily; subcutaneously) for 4 weeks. Ang II (50 μM, 5 μL) was microinjected by intracerebroventricular (i.c.v.) infusion and malondialdehyde (MDA) and thiol in the kidneys were measured. Results: MDA in the kidneys was increased by Ang II and doca-salt treatments. Both estradiol and Tst decreased the kidney's MDA. The level of thiol was higher in Hyper ‎groups and reversed after treatment with estradiol and Tst. Conclusions: Our findings suggest that central effect of Ang II on blood pressure and kidney ‎disease is accompanied with increased levels of oxidative stress in the kidneys. Indeed sex hormones change the ROS level in the kidneys after central ‎microinjection of Ang II.‎‎ [ABSTRACT FROM AUTHOR]

Background: This study investigated the effect of hydroalcoholic extract of Nigella sativa (N. sativa) and its active component, thymoquinone (TQ) on hypertension induced by angiotensin II (AngII), the main product of renin–angiotensin system (RAS). Methods: Seven animal groups (n=7 for each group) were used as follows: (1) control, (2) AngII (300 ng/kg), (3) AngII+losartan (Los; 10 mg/kg), (4) TQ (40 mg/kg)+AngII, and (5–7) three doses of N. sativa (200, 400, and 600 mg/kg)+AngII. Los and AngII were injected intravenously; TQ and extracts were injected intraperitoneally. In TQ and N. sativa-treated groups, 30 min after injection of the extract and TQ, AngII was injected. Cardiovascular parameters were recorded by power lab system after cannulation of femoral artery. The maximum changes (∆) of systolic blood pressure (SBP), mean arterial pressure (MAP), and heart rate (HR) were calculated and used for statistical analysis. Results: AngII significantly increased maximal ∆SBP, ∆MAP, and ∆HR compared with the control (p<0.001), and these effects significantly were blunted by Los. TQ and two higher doses (400 and 600 mg/kg) of N. sativa significantly could antagonize effect of AngII on ∆SBP, ∆MAP (p<0.05 to p<0.001). AngII-induced changes of HR are also significantly decreased by TQ and dose 600 mg/kg of extract (p<0.01 and p<0.05, respectively). Conclusions: The N. sativa and its component TQ have the beneficial effect on hypertension probably due to attenuation cardiovascular effects of AngII. [ABSTRACT FROM AUTHOR]

Background: Diabetes mellitus (DM) is a prime risk factor for cardiovascular disease. The convincing experimental and clinical evidence indicated that the onset of DM is closely associated with oxidative stress and that the generation of reactive oxygen species increases in both the types of diabetes. The aim of the present study was to evaluate the effect of Teucrium polium (TP) hydroalcoholic extract on the blood glucose, cholesterol, triglyceride, and oxidative stress markers of the heart and aorta in streptozotocin (STZ)-induced diabetic rats. Methods: The male Wistar rats assigned into six groups (n = 8 in each group): Control, diabetic, and diabetic rats treated with TP extract (100, 200, and 400 mg/kg) or met and metformin (300 mg/kg) formin (300 mg/kg) group, by daily gavage for 6 weeks. Diabetes was induced by injection of STZ (60 mg/kg, i.p). Serum lipids and glucose, malondialdehyde (MDA) level, total thiol level, and also the activities of Cu, Zn-superoxide dismutase (SOD) in the cardiac and aortic tissues were assessed. Results: TP extract reduced serum glucose, triglyceride and cholesterol. The MDA levels were reduced significantly in all TP-treated groups and metformin. Total thiol levels were improved in the heart and aorta of TP extract-treated groups and metformin compared to the diabetic rats. The activity of SOD in the cardiac and aortic tissues of TP extract- and metformin-treated groups was higher than diabetic group. Conclusions: The results showed that chronic administration of TP in STZ-induced diabetic rats could decrease blood glucose, cholesterol, and triglyceride and also attenuate the oxidative stress in the aortic and cardiac tissues. [ABSTRACT FROM AUTHOR]

Objective(s): : Renal ischemia-reperfusion injury (IRI) as a severe condition of acute kidney injury (AKI) is the most common clinical problem with high mortality rates of 35-60% deaths in hospital. Mesenchymal stem cells (MSC) due to unique regenerative characteristics are ideal candidates for the treatment of the ischemic injuries. This work is focused on the administration of MSC to IRI-induced AKI Wistar rats and evaluating their significance in AKI treatment. Material and Methods: Animals underwent surgical procedure and AKI was induced by 40 min bilateral renal pedicle clamping. Immediately after reperfusion, 2×106 rat bone marrow derived MSCs were injected via intra-parenchymal or intra-aortic route. Results: Animals subjected to AKI after days 1 and 3 showed significant increase in the serum creatinine and blood urea nitrogen (BUN) concentration along with a declined glomerular filtration rate (GFR) when compared with non-ischemic animals. On the other hand, treated animals showed a significant enhanced regeneration as compared to ischemic animals in both administration route groups. Conclusion: According to the results concluded from the renoprotective effects of MSC in IRI/AKI, MSCs could be considered as promising therapeutic approach for AKI in clinical applications. [ABSTRACT FROM AUTHOR]

Objective(s): Cholinergic neurons are important neurons in the Pedunculopontine tegmental nucleus (PPT). In this study, nicotinic receptor of the PPT in central cardiovascular regulation in the anesthetized rat was evaluated. Materials and Methods: Saline, acetylcholine (Ach; doses: 90 and 150 nmol), hexamethonium (Hexa; doses: 100 and 300 nmol) and higher doses of Hexa (300 nmol) + Ach (150 nmol) microinjected into the PPT. The femoral artery was cannulated and cardiovascular responses were continuously recorded by a power lab system. After injection of drugs, peak changes of mean arterial pressure (AMAP), systolic blood pressure (ASBP) and heart rate (AHR) calculated and compared with saline group. Results: The ASBP and AMAP significantly decreased by two doses of Ach (P<0.05 to P<0.001) but AHR did not change. Two doses 100 (P<0.05) and 300 nmol (P<0.01) of Hexa significantly increased AHR but did not alter the AMAP or ASBP. Co-injection of Hexa + Ach significantly strengthened the AHR induced by Hexa alone (P<0.01) but did not affect AMAP or ASBP. Conclusion: These results indicate that nicotinic receptor of the PPT has an inhibitory effect on AHR with no significant effect on AMAP or ASBP. [ABSTRACT FROM AUTHOR]

Objective: Oxidative stress plays a critical role in the development of hypercholesterolemia-induced complications. This study evaluated the effects of aspirin and Salix alba hydroethanolic extract on oxidative stress in the heart and kidney of hypercholesterolemic rabbits. Materials and Methods: The antioxidant activity, as well as total phenolic and salicin content of S. alba (Sa) extract were assessed by DPPH radical scavenging activity, Folin-Ciocalteu and HPLC methods, respectively. Animals were divided into two groups of control (fed with normal chow), and HD (fed with high cholesterol diet for 6 weeks). Then, hypercholesterolemic animals allocated to the following treatment groups: CHO (received HD), Sa extract (HD plus extract 60 and 120 mg/kg), and aspirin (HD plus aspirin 120 mg/kg) and received the treatments on a daily basis for 6 weeks. MDA, GSH, and nitrite concentrations as well as the activities of SOD and CAT were evaluated in cardiac and kidney tissues. Results: The scavenging activity, total phenolic content and salicin were 19.1 µg/ml (IC50), 153.75 ± 3.6 mg of gallic acid/g, and 18.03 µg/mg, respectively. In comparison to CHO group, MDA levels were diminished in Sa and ASA groups but GSH levels were improved. NO metabolites increased in the heart of Sa 120 mg/kg group and in the kidney of all Sa and ASA treated groups. SOD activity increased only in the heart of Sa groups and in the kidney of Sa and ASA groups. CAT activity increased in the heart and kidney tissues of all Sa and ASA treated groups. Conclusion: The results showed S. alba extract improved redox homeostasis in heart and kidney tissues of hypercholesterolemic rabbits. The extract antioxidant property may be related to its phenolic content. [ABSTRACT FROM AUTHOR]