Comparison of the neuroprotective effects of aspirin, atorvastatin, captopril and metformin in diabetes mellitus

Objective: The aim of this study was to investigate the effect of combined intake of a high dose of aspirin, atorvastatin, captopril and metformin on oxidative stress in the brain cortex and hippocampus of streptozotocin (STZ)-induced diabetic rats. Material and methods: Rats were randomly divided into the following 11 groups: control and diabetic (D), as well as 9 groups that were treated with metformin (M, 300 mg/kg) or aspirin (ASA, 120 mg/kg) alone or in different combinations with captopril (C, 50 mg/kg) and/or atorvastatin (AT, 40 mg/kg) as follows: (D + M), (D + ASA), (D + M + ASA), (D + M + C), (D + M + AT), (D + M + C + ASA), (D + M + C + AT), (D + M + AT + ASA) and (D + M + C + AT + ASA). The rats in treatment groups received drugs by gavage daily for six weeks. Serum lipid profile and levels of oxidative markers in the brain cortex and hippocampus tissues were evaluated. Results: The levels of malondialdehyde in the brain cortex and hippocampus in all the treated groups decreased significantly (p < 0.05). There was a significant increase in the total thiol concentration as well as catalase activity in treated rats in (M + AT), (M + C + ASA), (M + C + AT), (M + AT + ASA) and (M + C + AT + ASA) groups in cortex and hippocampus in comparison with the diabetic rats (p < 0.05). Also, the superoxide dismutase activity in all treated rats with medications was significantly increased compared to the diabetic rats (p < 0.05–0.01). Conclusion: Our findings showed that the combined use of high-dose aspirin, metformin, captopril and atorvastatin potentiated their antioxidant effects on the brain, and hence could potentially improve cognitive function with their neuroprotective effects on hippocampus

Effect of the cholinergic system of the lateral periaqueductal gray (lPAG) on blood pressure and heart rate in normal and hydralazine hypotensive rats

Objective(s): Due to the presence of the cholinergic system in the lateral periaqueductal gray (lPAG) column, the cardiovascular effects of Acetylcholine (ACH) and its receptors in normotensive and hydralazine (HYD) hypotensive rats in this area were evaluated.Materials and Methods: After anesthesia, the femoral artery was cannulated and systolic blood pressure (SBP), mean arterial pressure (MAP), heart rate (HR), and also electrocardiogram for evaluation of low frequency (LF) and high frequency (HF) bands, important components of heart rate variability (HRV), were recorded. ACH, atropine (Atr, a muscarinic antagonist), and hexamethonium (Hex, an antagonist nicotinic) alone and together microinjected into lPAG, changes (Δ) of cardiovascular responses and normalized (n) LF, HF, and LF/HF ratio were analyzed.Results: In normotensive rats, ACH decreased SBP and MAP, and enhanced HR while Atr and Hex did had no effects. In co-injection of Atr and Hex with ACH, only ACH+Atr significantly attenuated parameters. In HYD hypotension, ACH had no affect but Atr and Hex significantly improved the hypotensive effect. Co-injection of Atr and Hex with ACH decreased the hypotensive effect but the effect of Atr+ACH was higher. In normotensive rats, ACH decreased nLF, nHF, and nLF/nHF ratio. These parameters in the Atr +ACH group were significantly higher than in ACH group. In HYD hypotension nLF and nLF/nHF ratio increased which was attenuated by ACH. Also, Atr+ACH decreased nLF and nLF/nHF ratio and increased nHF.Conclusion: The cholinergic system of lPAG mainly via muscarinic receptors has an inhibitory effect on the cardiovascular system. Based on HRV assessment, peripheral cardiovascular effects are mostly mediated by the parasympathetic system

Anti-inflammatory, immunomodulatory and anti-oxidant effects of Ocimum basilicum L. and its main constituents: A review

Ocimum basilicum L. (O. basilicum) is an ornamental and therapeutic plant with various pharmacological effects and medical applications. In this article, detailed information on the anti-oxidant, immunomodulatory, and anti-inflammatory properties of O. basilicum and its main constituents was provided. The literature survey of the different databases until the end of November 2021 was explored on the immunomodulatory, anti-inflammatory and anti-oxidant effects of the herb and its constituents. The plant and its constituents showed diverse pharmacological effects including immunomodulatory, anti-inflammatory and anti-oxidant properties by improving of the inflammatory mediators including interleukin (IL)-10, IL-4, tumor necrosis factor-alpha (TNF-α), interferon gamma (IFN-γ), nitric oxide (NO), serum levels of IFN-γ, IL10 and IL-4, IgG, IgM and phospholipase A2 (PLA2), immunoglobulin E (IgE), total protein (TP), oxidant and anti-oxidant markers. O. basilicum and its main constituents therefore, could be effective on the treatment of diseases associated with inflammation, immune dysregulation and oxidative stress. The present review article provides readers with organized information about the anti-oxidant, immunomodulatory, and anti-inflammatory properties of O. basilicum

Effects of Zataria multiflora Extract and Carvacrol on Doxorubicin-Induced Oxidative Stress in Rat Brain

Background: Due to the antioxidant effects of Zataria multiflora (ZM) and Carvacrol (CAR) in various problems and the prominent role of the ROS in neurotoxicity induced by Doxorubicin (DOX), this study was designed to investigate the effects of ZM hydroalcoholic extract and CAR on DOX-induced oxidative stress in rat brain. Methods: 24 male rats were randomly divided into four groups including: 1)Control ,2)Doxorubicin (DOX) that received DOX via a tail vein on the first day of the study, 3,4) ZM+DOX and CAR+DOX which received ZM and CAR by gavage for 28 consecutive days. Brain tissue removed for redox markers evaluation. Results: MDA level in the DOX group was significantly increased compared to control group while in treated groups did not show any significant changes in comparison with the DOX group. Also, Thiol content in DOX group showed significant reduction compared to control group. Thiol contents in treated groups showed no significant difference compared to DOX group. Catalase (CAT) activity, an antioxidant enzyme, in the DOX group were significantly decreased compared to control group and increased in treated rats in comparison with the DOX group. Activity of Superoxide dismutase (SOD), an antioxidant enzyme, in the DOX group was significantly reduced compared to control group and increased in treated rats in comparison with the DOX group. Conclusion: The present study showed that ZM hydroalcoholic extract and CAR could inhibit DOX induced oxidative stress of the brain mainly with effect on the enzymatic antioxidant defense system

Protective effects of long-term administration of Ziziphus jujuba fruit extract on cardiovascular responses in L-NAME hypertensive rats

Objective: Ziziphus jujuba stimulates the release of nitric oxide (NO).  Because NO is involved in cardiovascular regulations, in this study the effects of hydroalcoholic extract of Z. jujuba on cardiovascular responses in acute NG-nitro-L-arginine methyl ester (L-NAME) hypertensive rats were evaluated. Materials and Methods: Rats were divided into 6 group (n=6): 1) saline, 2) L-NAME received (10mg/kg) intravenously, 3) sodium nitroprusside (SNP) (50µg/kg)+L-NAME group received SNP before L-NAME and 4-6) three groups of Z. jujuba (100, 200 and 400mg/kg) that treated for four weeks and on the 28th day, L-NAME was injected. Femoral artery and vein were cannulated for recording cardiovascular responses and drug injection, respectively. Systolic blood pressure (SBP), Mean arterial pressure (MAP) and heart rate (HR) were recorded continuously. Maximal changes (∆) of SBP, MAP and HR were calculated and compared to control and L-NAME groups. Results: In L-NAME group, maximal ΔSBP (L-NAME: 44.15±4.0 mmHg vs control: 0.71±2.1 mmHg) and ΔMAP (L-NAME: 40.8±4.0 mmHg vs control: 0.57±1.6 mmHg) significantly increased (p0.05). All doses of Z. jujuba attenuated maximal ∆SBP and ∆MAP induced by L-NAME but only the lowest dose (100 mg/kg) had significant effects (ΔSBP: 20.36±5.6 mmHg vs L-NAME: 44.1±4.0 mmHg and ΔMAP: 20.8±4.5 mmHg vs L-NAME: 40.8±3.8 mmHg (p0.05). Conclusion: Because long-term consumption of Z. jujuba extract, especially its lowest dose, attenuated cardiovascular responses induced by L-NAME, we suggest that Z. jujuba has potential beneficial effects in prevention of hypertension induced by NO deficiency

Doxorubicin-induced renal inflammation in rats: Protective role of Plantago major

Objective: The aim of the present study was to evaluate the possible protective effect of Plantago major (P. major) extract against doxorubicin (DXR)-induced renal inflammation in rats. Materials and Methods: 80 male albino rats were randomly divided into 8 groups as follows: control, DXR, Ext (extract) 600, Ext1200, dexamethasone+DXR, vitamin E+DXR, Ext600+DXR, and Ext1200+DXR. Duration of the study was 35 days and DXR was intravenously injected on the 7th day of the experiment. Tumor necrosis factor-alpha (TNF-α) production and monocyte chemoattractant protein-1 (MCP-1) expression levels were assessed in the left kidney. Serum creatinine concentration and osmolarity were determined on the 1st, 14th, 21st, 28th and 35th days of the experiment. Results: DXR caused a significant increase in renal expression of MCP-1 and TNF-α production compared to control animals. Administration of dexamethasone, vitamin E and P. major extract significantly improved the expression of these inflammatory mediators compared to DXR group. Compared to day 1 in DXR group, serum osmolarity showed a significant increase on days 21, 28 and 35. Also, on these days, serum osmolarity in DXR group was significantly higher than that on the same days in control group. In Vit E+DXR and Ext 1200+DXR groups, there was no significant changes in serum osmolarity among different days of the study. However, in these groups, serum osmolarity on days 21, 28 and 35 showed a significant decrease compared to the same days in DXR group. Conclusion: Present results suggest that hydroethanolic extract of P. major protected renal tissue against DXR–induced renal inflammation

Comparative Effects of Metformin and Glibenclamide on Aortic Reactivity to Vasodilator and Vasoconstrictor Agents in STZ-Induced Diabetic Rats: Comparative effect of metformin and glibenclamide in diabetic rats

Diabetes is an important risk factor for cardiovascular events. Endothelial dysfunction is the main cause of disability and death in diabetic patients. The present study investigates the effects of metformin and glibenclamide on vasoconstrictive and vasodilative responses in the diabetic rat aorta. Rats were divided into four experimental groups (control, STZ-diabetic, metformin and glibenclamide treated diabetic rats). The treated rats received metformin (300 mg/kg) or glibenclamide (5 mg/kg) daily by gavage for 6 weeks.Thoracic aortic rings were mounted in an organ bath system, then contractile and dilatation responses induced by acetylcholine (ACh), phenylephrine (PE), potassium chloride (KCl), and sodium nitroprusside (SNP) were evaluated in different situations.Blood glucose level in glibenclamide group in days 24 and 45 were significantly lower than diabetic group. Metformin and glibenclamide significantly reduced the contractile responses to higher concentrations of PE (10-6 - 10-5 M) compared to diabetic group. Metformin and glibenclamide significantly reduced the contractile responses to concentrations of KCl (50 and 60 mM) compared to diabetic group. The relaxation responses to Ach 10-8 M, was increased in metformin and glibenclamide groups compared to the diabetic group. The relaxation responses to Ach 10-7 - 10-5 M were significantly higher in both treated groups compared to diabetic group. The chronic administration of metformin or glibenclamide has a significant hypoglycemic effect and improves aortic reactivity to vasoconstrictor and vasodilator agents in STZ-induced diabetic rats. No significant difference was found regarding the effects of metformin and glibenclamide on vasoconstrictive and vasodilative responses in aorta