Anti-inflammatory, anti-oxidant and anti-apoptotic effects of olive leaf extract in cardiac tissue of diabetic rats.

OBJECTIVES: Inflammatory process and apoptosis are involved in the pathogenesis of cardiac injury and oxidative damage caused by diabetes mellitus. The cardioprotective effects of standardized aqueous ethanolic olive leaf extract (OLE), metformin (as a cardiovascular protective agent) and valsartan (as an angiotensin receptor blocker) in the streptozotocin-induced diabetic rats were evaluated. METHODS: Wistar rats divided into control, diabetic, OLE-treated (100, 200 and 400 mg/kg), metformin (300 mg/kg)-treated, valsartan (30 mg/kg)-treated and metformin/valsartan-treated diabetic groups. Biochemical parameters, including malondialdehyde (MDA) levels, superoxide dismutase (SOD) and catalase (CAT) activates, and the total contents of thiol were measured, and histopathological and gene expression studies were done on cardiac tissues. Fasting blood sugar (FBS) and cardiac injury markers were examined in serum. KEY FINDINGS: FBS; the serum levels of lactate dehydrogenase (LDH), creatine kinase-muscle/brain (CK-MB), aspartate aminotransferase (AST); and heart tissue MDA levels due to diabetes were significantly alleviated by OLE treatment (effect size; ηp2 = 0.934, 0.888, 0.848, 0.888 and 0.879, respectively), and SOD and CAT activity and the thiol content in heart tissue were significantly increased (effect size; ηp2 = 0.770, 0.749 and 0.753, respectively). Interleukin-1ß (IL-1ß), tumour necrosis factor-α (TNF-α) and the number of infiltrating inflammatory cells were reduced in cardiac tissues of OLE-treated groups compared with the diabetic rats (effect size; ηp2 = 0.969 and 0.949, respectively). OLE up-regulated BCL2 gene expression and down-regulated BAX gene expression in cardiac tissue (effect size; ηp2= 0.490 and 0.522, respectively). CONCLUSION: OLE in a dose-dependent manner ameliorates cardiac damage in diabetic cardiomyopathy, perhaps through attenuating inflammation, oxidative stress and apoptosis.

Diabetic cardiomyopathy was attenuated by cinnamon treatment through the inhibition of fibro-inflammatory response and ventricular hypertrophy in diabetic rats.

Diabetic cardiomyopathy (DCM) is a chronic complication of diabetes that emphasizes the urgency of developing new drug therapies. With an illustrious history in traditional medicine to improve diabetes, cinnamon has been shown to possess blood lipids lowering effects and antioxidative and anti-inflammatory properties. However, the extent to which it protects the diabetic heart has yet to be determined. Forty-eight rats were administered in the study and grouped as: control; diabetic; diabetic rats given 100, 200, or 400 mg/kg cinnamon extract, metformin (300 mg/kg), valsartan (30 mg/kg), or met/val (combination of both drugs), via gavage for six weeks. Fasting blood sugar (FBS) and markers of cardiac injury including creatine kinase-muscle/brain (CK-MB), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) were evaluated in blood samples. Malondialdehyde (MDA) levels, the total contents of thiol, superoxide dismutase (SOD), and catalase (CAT) activities were measured. Histopathology study and gene expression measurement of angiotensin II type 1 receptor (AT1), atrial natriuretic peptide (ANP), beta-myosin heavy chain (ß-MHC), and brain natriuretic peptide (BNP) were done on cardiac tissue. FBS and cardiac enzyme indicators were reduced in all treated groups. A reduction in MDA level and enhancement in thiol content alongside with increase of SOD and CAT activities were observed in extract groups. The decrease of inflammation and fibrosis was obvious in treated groups, notably in the high-dose extract group. Furthermore, all treated diabetic groups showed a lowering trend in AT1, ANP, ß-MHC, and BNP gene expression. Cinnamon extract, in addition to its hypoglycemic and antioxidant properties, can prevent diabetic heart damage by alleviating cardiac inflammation and fibrosis. PRACTICAL APPLICATIONS: This study found that cinnamon extract might protect diabetic heart damage by reducing inflammation and fibrosis in cardiac tissue, in addition to lowering blood glucose levels and increasing antioxidant activity. Our data imply that including cinnamon in diabetic participants' diets may help to reduce risk factors of cardiovascular diseases.

The effect of HTLV1 infection on inflammatory and oxidative parameters in the liver, kidney, and pancreases of BALB/c mice.

Viral infections are linked to the progression of inflammatory reactions and oxidative stress that play pivotal roles in systemic diseases. To confirm this phenomenon, in the present study, TNF-α level and oxidative stress markers were examined in the liver, kidney, and pancreas of HTLV1-infected male BALB/c mice. To this end, twenty BALB/c mice were divided into HTLV1-infected mice that were inoculated with 1-million HTLV1-infected cells (MT-2), and the control groups. Two months after inoculation, the peripheral blood, mesenteric lymph nodes, liver, kidney, and pancreas were collected after deep anesthetization of mice (ketamine, 30 mg/kg). The extracted DNA of mesenteric lymph nodes was obtained to quantify proviral load (PVL) using quantitative real-time polymerase chain reaction (qRT-PCR). The levels of lipid peroxidation, total thiol (SH), nitric oxide (NO), TNF-α, catalase (CAT), and superoxide dismutase (SOD) activities were examined in the liver, kidney, and pancreases. Furthermore, histopathological changes in the liver and kidney were evaluated. In liver tissue, the levels of MDA, TNF-α, and blood cell infiltration were significantly increased, and the levels of CAT and SOD were significantly decreased. In the kidney, a reduction in SOD, CAT, and total SH and an increase in MDA and NO were observed. In the pancreas, CAT activity, total SH, and SOD were decreased, and the levels of MDA and NO were enhanced. In terms of TNF-α production, it has been shown that the level of this inflammatory cytokine was increased in the liver, kidney, and pancreas. The HTLV1 may have a role in inducing inflammatory reactions and oxidative stress pathways in the tissues.

Comparing the effects of Portulaca oleracea seed hydro-alcoholic extract, valsartan, and vitamin E on hemodynamic changes, oxidative stress parameters and cardiac hypertrophy in thyrotoxic rats.

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.

The effect of Cinnamomum cassia extract on oxidative stress in the liver and kidney of STZ-induced diabetic rats.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

The Comparison of Antioxidant Effect of Aspirin, Metformin, Atorvastatin and Captopril Co-administration in the Heart and Kidney Tissues of Diabetic Rats.

The present study investigated the effects of co-administration of aspirin, metformin, atorvastatin and captopril on serum lipid profile and oxidative stress in the heart and kidney of streptozotocin-induced diabetic rats. In this study, rats were randomly divided into the following eleven groups: control (Cont.), 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), 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 daily received drugs by gavage for six weeks. Finally, serum lipid profile and levels of oxidative markers in the heart and kidney tissues were evaluated. In diabetic rats, blood levels of glucose, cholesterol, TG (triglyceride), LDL (low-density lipoprotein), MDA (malondialdehyde) and AIP (atherogenic index of plasma) significantly increased but those of HDL (high-density lipoprotein) and total thiol as well as SOD (superoxide dismutase) and CAT (catalase) activities significantly decreased. Treatment with different combinations of C, ASA, AT and M significantly ameliorated these parameters. This study showed that co-administration of ASA, M, C and AT, could improve glucose and lipid metabolism and oxidative stress markers in the kidneys and heart tissues of diabetic rats more markedly than the administration of these drugs alone.

Human T-Cell Leukemia Virus Type 1 Changes Leukocyte Number and Oxidative Stress in the Lung and Blood of Female BALB/c Mice.

BACKGROUND: Human T-cell leukemia virus type 1(HTLV-1) infection is likely to induce nonneoplastic inflammatory pulmonary diseases. Therefore, an experimental study was conducted to evaluate the leukocytes' number alteration and oxidative stress in the lung and blood of HTLV-1-infected BALB/c mice, which could be of benefit for the recognition of HTLV-1 mechanism in the induction of pulmonary disorders. MATERIALS AND METHODS: Twenty female BALB/c mice were divided into two groups of control and HTLV-1-infected animals. The HTLV-1-infected group was inoculated with 106 MT-2 HTLV-1-infected cells. Two months later, the infection was confirmed using real-time polymerase chain reaction, and then lung pathological changes, total and differential inflammatory cell counts in the blood and bronchoalveolar lavage fluid (BALF), along with oxidative stress biomarker levels in the BALF and lung tissue were evaluated. RESULTS: In the HTLV-1-infected group, the peribronchitis score (P < 0.01), the number of total leukocytes, neutrophils, lymphocytes, and monocytes (P < 0.05) in the blood and BALF were increased. The number of eosinophils in the blood of the HTLV-1-infected group was higher than in the control group (P < 0.01), whereas the number of basophils of BALF was increased in the HTLV-1-infected group (P < 0.001). The lung and BALF oxidative stress results showed that the MDA level was increased, while the total thiol level and superoxide dismutase activity were decreased in the HTLV-1-infected group (P < 0.01). CONCLUSION: The HTLV-1 infection seems to induce pulmonary inflammatory reactions by recruiting leukocytes as well as inducing oxidative stress in the lung tissue.

Cardioprotective effects of Fenugreek (Trigonella foenum-graceum) seed extract in streptozotocin induced diabetic rats.

Introduction: Inadequate control of diabetes mellitus (DM) leads to considerable cardiovascular implications like diabetic cardiomyopathy (DCM). Cardiomyocyte apoptosis is one of the main mechanisms of DCM pathogenesis associated with hyperglycemia, oxidative stress, inflammation, hyperlipidemia and several other factors. Trigonella foenum-graecum (Fenugreek) has been long used as a traditional medicine and has many therapeutic effects, including anti-diabetic, anti-hyperlipidemia, anti-inflammatory and anti-oxidant properties. The current study aimed to investigate cardioprotective effects of fenugreek seed on diabetic rats. Methods: Diabetes was induced in forty-two male rats by injection of streptozotocin (STZ) (60 mg/ kg). Diabetic animals were treated with three different doses of fenugreek seed extract (50, 100 and 200 mg/kg) or metformin (300 mg/kg) for six weeks by gavage. Nondiabetic rats served as controls. Glucose, cholesterol, and triglycerides levels were measured in the blood samples, and oxidative stress markers as well as gene expression of ICAM1 , Bax and Bcl2 were assessed in the cardiac tissues of the experimental groups. Results: Diabetic rats exhibited increased serum glucose, cholesterol and triglycerides levels, elevated markers of oxidative stress thiobarbituric acid-reacting substances (TBARS) levels , total thiol groups (SH), catalase (CAT) and superoxide dismutase (SOD) activity, and enhanced apoptosis cell death (ratio of Bax/Bcl2). Fenugreek seed extract considerably improved metabolism abnormalities, attenuated oxidative stress and diminished apoptosis index. Conclusion: Our study suggests that fenugreek seed may protect the cardiac structure in STZ-induced diabetic rats by attenuating oxidative stress and apoptosis.

The vasodilatory effect of Apium graveolens L (celery) seed in isolated rat aorta: The roles of endothelium, calcium and potassium channels.

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.

Ginger (Zingiber Officinale Roscoe) Extract Protects the Heart Against Inflammation and Fibrosis in Diabetic Rats.

BACKGROUND: Fibrosis and inflammation in the heart of patients with diabetes mellitus alongside increased production of free radicals and collagen are together known as diabetic cardiomyopathy. Ginger rhizome has antidiabetic, antioxidant and anti-inflammatory effects. Thus, we investigated the effect of ginger extract on diabetes-induced cardiomyopathy in streptozotocin-induced diabetic rats. METHODS: Animals were divided into 7 groups: control; diabetic; diabetic treated with different doses of ginger extract of 100, 200 and 400 mg/kg; metformin (200 mg/kg); and metformin-valsartan (200 and 30 mg/kg, respectively). Serum levels of glucose, aspartate aminotransferase, lactate dehydrogenase and creatine kinase-muscle/brain were measured. Fibrosis and inflammation were determined by histologic assessment. Gene expression of transforming growth factor (TGF)-ß1, TGF-ß3 and angiotensin II type 1 receptor was evaluated by real-time polymerase chain reaction in heart tissue. RESULTS: Serum glucose level in all treated groups, except for the ginger extract 100-mg/kg group, was significantly lower than in the diabetic group. Serum levels of aspartate aminotransferase, lactate dehydrogenase and creatine kinase-muscle/brain were significantly reduced in all treated groups compared with the diabetic group. In the study of fibrosis, collagen amount in the heart tissue of all treated groups, except the ginger extract 100-mg/kg group, was significantly lower than in the diabetic group. Inflammatory cell infiltrates were decreased, and disarrangement was improved in cardiac tissues of all treated groups compared with the diabetic group. Expression of angiotensin II type 1 receptor and TGF-ß1 and TGF-ß3 genes in all treated groups downregulated compared with the diabetic group. CONCLUSIONS: Treatment by ginger extract reduced myocardial fibrosis and inflammation in the course of diabetic cardiomyopathy, possibly through regulation of the expression of genes involved in the SMAD/TGF-ß pathway.

Antihypertensive Effects of Standardized Asafoetida: Effect on Hypertension Induced by Angiotensin II.

BACKGROUND: Asafoetida is an oleo-gum-resin obtained from the rhizome of Ferula assa-foetida plant that its effects on hypertension have been reported. This study examines the effect of aqueous extract of asafoetida on the cardiovascular parameters in acute hypertension induced by angiotensin II (AngII). MATERIALS AND METHODS: Thirty-six male rats were divided into six groups including Group 1: control; Group 2: AngII (50 ng/kg, intravenous); Group 3: losartan (Los; 10 mg/kg, i. p) + AngII; and Groups 4, 5, and 6 that received three doses of asafoetida (10, 30, and 60 mg/kg, i. p), separately. Los and extract were injected 30 min before hypertension induced by AngII. The femoral artery was cannulated and was connected to a pressure transducer, and cardiovascular parameters (systolic blood pressure [SBP], mean arterial pressure [MAP], and heart rate [HR]) were continuously recorded by a Power Lab system. The changes (Δ) of parameters were calculated and used for statistical analysis. RESULTS: AngII significantly increased the value of Δ SBP and Δ MAP compared to the control and significantly decreased Δ HR value. Injection of Los attenuated increased cardiovascular responses by AngII. Three doses of asafoetida ameliorated cardiovascular responses by AngII. Three doses of asafoetida decreased the Δ HR non significantly compared to AngII. CONCLUSION: Our results indicated that aqueous extract of asafoetida ameliorated cardiovascular responses in acute hypertension induced by AngII. This effect in a lower dose was more effective and comparable with Los. Therefore, a part of antihypertensive effect of asafoetida is mediated through inhibition of the AngII receptor type 1 receptor of AngII.

The Protective Effects of Pharmacologic Postconditioning of Hydroalcoholic Extract of Nigella sativa on Functional Activities and Oxidative Stress Injury During Ischemia-Reperfusion in Isolated Rat Heart.

Oxidative stress is known to act as the trigger of cardiac damage during ischemia-reperfusion (I/R) injury. Postconditioning (PoC) is employed to minimize the consequences of ischemia at the onset of reperfusion. Regarding the well-known antioxidant properties of Nigella sativa (Ns), the aim of this study was to investigate whether Nigella sativa postconditioning (Ns-PoC) could reduce IRI by lowering the formation of reactive oxygen species (ROS). Isolated rat hearts were perfused with the Langendorff apparatus, which were subjected to 20 min of preperfusion, 20 min of global ischemia, followed by 40 min of reperfusion. At the onset of reperfusion, based on the type of intervention group, a 10-min period of Krebs flow was developed along with the treatment, and then the reperfusion with Krebs solution was conducted for 30 min. Heart rate (HR) and left ventricular pressure (LVP) were recorded by isometric transducers connected to a data acquisition system. Thiobarbituric acid reactive substances (TBARS), 4-hydroxynonenal (4-HNE) levels, total thiol groups (-SH) levels, superoxide anion dismutase (SOD), and catalase (CAT) activities in myocardial tissues were detected to evaluate the oxidative stress damage degree. Ns-PoC significantly improved cardiodynamic parameters including left ventricular developed pressure (LVDP), rate pressure product (RPP), and the maximum up/down rate of the left ventricular pressure (± dp/dt) as well as SH groups, SOD, and CAT activities. Moreover, it decreased MDA and 4-HNE levels during early reperfusion. The results of this study showed that Ns-PoC ameliorated cardiac functions in isolated rat heart during I/R injuries by improving myocardial oxidative stress states, which may be related to the antioxidant effect of Ns.

Trigonella foenum-graceum seed (Fenugreek) hydroalcoholic extract improved the oxidative stress status in a rat model of diabetes-induced memory impairment.

Background The antidiabetic and antioxidant effects of Trigonella foenum-graceum have been suggested. The effects of hydroalcoholic extract of the plant seeds and metformin against the diabetes-induced memory impairment were investigated. Materials and methods The rats were treated: (1) control, (2) diabetic (3-6) and diabetic rats treated by 50, 100 and 200 mg/kg of the plant extract or metformin. The rats were diabetic by streptozotocin (STZ, 55 mg/kg). After the passive avoidance test, malondialdehyde (MDA), nitric oxide (NO) metabolites, total thiol (SH), catalase (CAT) and superoxide dismutase (SOD) were determined in the brain. Results In the diabetic group, at 3, 24 and 48 h after receiving a shock, the latency to enter the dark room was lower than for the controls (p < 0.001). All doses of the extract and metformin increased the latencies to enter the dark at 3 and 24 h after the shock treatment (p < 0.05-p < 0.001). Additionally, the two higher doses of the extract and metformin increased the latency at 48 h after the shock (p < 0.05-p < 0.001). Diabetes also elevated MDA and NO metabolites, while it reduced thiol, SOD and CAT in the hippocampal and cortical tissues (p < 0.001). Treatment of the diabetic animals by the highest dose of the extract and also metformin reduced the MDA and NO metabolites, while it improved thiols, SOD and CAT (p < 0.01-p < 0.001). Conclusions Based on our findings, metformin and the hydro-alcoholic extract from the T. foenum-graceum seed prevented memory deficits resulting from diabetes. Preventing oxidative damage in the brain may at least, in part, be responsible for the positive effects of the extract and metformin.

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.

Nigella sativa L. seed regulated eNOS, VCAM-1 and LOX-1 genes expression and improved vasoreactivity in aorta of diabetic rat.

ETHNOPHARMACOLOGICAL RELEVANCE: Nigella sativa L. seed has been widely used in traditional medicine for the treatment of diabetes. The major reason for vascular complications in diabetic patients is endothelial dysfunction. However, the impact of N. sativa seed on endothelial dysfunction in diabetes remains unclear. AIM OF THE STUDY: This study was conducted to evaluate the effect of the hydroalcoholic extract of N. sativa seed on eNOS, VCAM-1, and LOX-1 genes expression and the vasoreactivity of aortic rings to acetylcholine (Ach) in streptozotocin (STZ)-induced diabetic rat. MATERIALS AND METHODS: Treated rats received N. sativa seed extract (100, 200, and 400 mg/kg) daily by gavage for 6 weeks. The fasting blood glucose and lipids were measured and atherogenic index of plasma (AIP) was calculated. The endothelium-dependent vasoreactivity responses of isolated aortic rings were evaluated in the presence of cumulative concentrations of Ach (10-8-10-5 M). eNOS, VCAM-1, and LOX-1 genes expression in aortic tissue was assessed by using real time polymerase chain reaction (PCR). RESULTS: Male diabetic Wistar rats treated with N. sativa seed extract for six weeks reduced serum glucose and lipids and improved AIP. The vasorelaxant responses of aortic rings to Ach were markedly improved. N. sativa seed significantly increased eNOS in mRNA expression level and function, while it decreased VCAM-1 and LOX-1 expressions in vascular cells of aortic tissue which assessed only in mRNA level. CONCLUSIONS: The results of this study showed that N. sativa seed more likely, has antidiabetic and antihyperlipidemic properties and improved vasoreactivity, endothelial dysfunction, and vascular inflammation in diabetic rats' aorta.

The effects of estradiol and testosterone on renal tissues oxidative after central injection of angiotensin II in female doca - salt treated rats.

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. .

Teucrium polium L. Improved Heart Function and Inhibited Myocardial Apoptosis in Isolated Rat Heart Following Ischemia-Reperfusion Injury.

OBJECTIVES: Myocardial reperfusion is the only logical cure for ischemic heart disease. However, ischemic-reperfusion (I/R) injury is one of the underlying factors facilitating and accelerating the apoptosis in the myocardium. This study set to investigate the impact of Teucrium polium (TP) hydro-alcoholic extract on I/R induced apoptosis in the isolated rat heart. METHODS: Isolated rat hearts were classified into six groups. The control samples were subjected to 80 min of perfusion with Krebs-Henseleit bicarbonate (KHB) buffer; in control-ischemia group, after primary perfusion (20 min) the hearts were exposed to global ischemia (20 min) and reperfusion (40 min). Pretreated groups were perfused with 500 µM of vitamin C and various TP concentrations (0.5, 1, 2 mg/ml) for 20 min, and then the hearts were exposed to ischemia and reperfusion for 20 min and 40 min, respectively. Cardiodynamic parameters including rate pressure product (RPP), heart rate (HR), the maximum up/down rate of left ventricular pressure (±dp/dt), left ventricular developed pressure (LVDP), and coronary artery flow (CF) were achieved from Lab Chart software data. The Bax and BCl-2 gene expressions were measured in heart samples. RESULTS: Hearts treated with TP extract and vit C represented a meaningful improvement in cardiac contractile function and CF. The overexpression of Bcl-2, downregulation of Bax, and improvement of apoptotic index (Bax/Bcl-2) were observed in pretreated TP extract and vit C hearts. CONCLUSION: The TP extract was found to ameliorate the cardiac function in the reperfused myocardium. Also, it can hinder apoptotic pathways causing cardioprotection.

The standardized extract of Nigella sativa and its major ingredient, thymoquinone, ameliorates angiotensin II-induced hypertension in rats.

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.

HTLV-1 infection-induced motor dysfunction, memory impairment, depression, and brain tissues oxidative damage in female BALB/c mice.

AIMS: The HTLV-1 infection is associated with a neuro-inflammatory disease. In the present study, the behavioral consequences and brain oxidative damages were evaluated in HTLV-1-infected BALB/c mice. MATERIAL AND METHODS: 20 female BALB/c mice were divided into two groups comprising control and HTLV-1-infected. The HTLV-1-infected group was inoculated with a 106 MT-2 HTLV-1-infected cell line. Two months later, the behavioral tests were conducted. Finally, oxidative stress was assessed in the cortex and hippocampus tissues. KEY FINDINGS: In the HTLV-1-infected group, running time and latency to fall, travel distance and time spent in the peripheral zone, total crossing number and total traveled distance in open field test, the latency of entrance into the dark compartment in the passive avoidance test, the new object exploration percentage, and discrimination ratio were significantly lower than in the control group. The immobility time, time spent in the dark compartment in passive avoidance test, and total exploration time significantly increased in the HTLV-1-infected group compared to the control group. In the cortical tissue of the HTLV-1 group, the malondialdehyde levels were elevated while the total thiol levels decreased in comparison to the control group. The activity of superoxide dismutase in the cortical and hippocampal tissues, and catalase activity in cortical tissue significantly decreased in the HTLV-1 group in comparison to the control group. SIGNIFICANCE: The HTLV-1 infection seems to induce depression-like behavior, motor dysfunction, disruption in working and fear memory and also oxidative stress in the cortex and hippocampus.

In vivo effects of allogeneic mesenchymal stem cells in a rat model of acute ischemic kidney injury.

OBJECTIVES: 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.