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Background: Hypertension is associated with cardiovascular dysfunction, dysregulation of the antioxidant system and alteration of the level of some enzymes in the metabolic pathway. The possible modulatory effect of acute renal denervation (ARD) on cardiovascular function and the antioxidant system is still a subject of intense debate. This study sought to ascertain the ameliorative effects of ARD on cardiovascular parameters, antioxidant system, creatine kinase and lactate dehydrogenase levels. Methods: Thirty-six Sprague-Dawley rats (5-6 weeks old) were divided into 6 groups of 6 animals each consisting of Normal Salt, High Salt, Normal Salt + Sham Denervation, High Salt + Sham Denervation, Normal Salt + Renal Denervation and High Salt + Renal Denervation. Induction of hypertension with 8 % salt in the diet lasted for 8 weeks. Renal or Sham denervation was thereafter done on selected groups. At the end of the experimental period, cardiovascular parameters, plasma antioxidant status, plasma creatine kinase (CK) and lactate dehydrogenase (LDH) levels were assessed. Significance level was set at p < 0.05. Results: Salt-loading significantly increased systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MABP), rate pressure product (RPP) while reducing superoxide dismutase (SOD), reduced glutathione (GSH) and catalase (CAT). Acute renal denervation significantly (p < 0.0001) reduced SBP, DBP, MABP, RPP, LDH and norepinephrine level while increasing SOD, GSH and CAT. ARD did not significantly alter CK level. Conclusion: Acute renal denervation, by reducing sympathetic activity, ameliorates cardiovascular and antioxidant functions as well as reduces LDH level without significantly altering CK level in salt-induced hypertension.
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Liver diseases have gained increasing attention due to their substantial impact on health, independently as well as in association with cardio-metabolic disorders. Studies have suggested that glutathione and adenosine assist in providing protection against oxidative stress and inflammation while glucocorticoid (GC) therapy has been associated with chronic inflammatory disorders, even in pregnancy. The implications of Glucocorticoid exposure on maternal health and fetal growth is a concern, however, the possible role of glutathione and adenosine has not been thoroughly investigated. The study therefore hypothesize that exposure to glucocorticoids leads to depletion of hepatic glutathione and adenosine levels, contributing to oxidative stress and tissue injury. Additionally, we aim to investigate whether the effects of glucocorticoids on hepatic health are pregnancy dependent in female rats. Twelve Pregnant and twelve age-matched non-pregnant rats were used for this study; an exogenous administration of glucocorticoid (Dex: 0.2â¯mg/kg) or vehicle (po) was administered to six pregnant and six non-pregnant rats from gestational day 14 to 19 or for a period of 6 days respectively. Data obtained showed that GC exposure led to a decrease in hepatic glucose-6-phosphate dehydrogenase, glutathione peroxidase, GSH/GSSG ratio and adenosine content in both pregnant and non-pregnant rats. In addition, increased activities of adenosine deaminase and xanthine oxidase, along with increased production of uric acid and increased levels of lactate dehydrogenase, aspartate aminotransferase, alanine transferase, alkaline phosphatase and gamma-glutamyl transferase were observed. In summary, the study indicates that GC-induced liver damage is underlined by depleted hepatic adenosine and glutathione levels as well as elevated markers of tissue inflammation and/or injury. Furthermore, the findings suggest that the effects of GC exposure on hepatic health are pregnancy independent.
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BACKGROUND: Smoking is associated with dysregulation of the antioxidant system and addiction. AIM: This study sought to ascertain the effect of Nigella Sativa (NS) oil on the antioxidant system, nicotine/tobacco addiction as well as the expressions of α4ß2 nicotinic (nAChR) and dopamine type-2 (DRD2) receptors in selected brain regions of the rat. METHODS: Thirty male Sprague-Dawley rats were divided into 6 groups comprising of vehicle-treated control, NS oil only, Smoke only, Smoke + NS oil, Nicotine only and Nicotine + NS oil. Animals were passively exposed to cigarette smoke or nicotine vapour for 12 weeks, however, NS oil treatment commenced from 9th-12th week of the experimental duration. RESULTS: Nicotine vapour and cigarette smoke-induced increase in cotinine level were significantly ameliorated by NS treatment. Cigarette smoke or nicotine vapour exposure significantly (p<0.05) decreased the level of antioxidant enzymes while increasing malondialdehyde level in the brain homogenates of the rats. Administration of NS oil significantly (p<0.05) reversed the reduced antioxidant level. Cigarette-smoke also significantly increased α4-nAChR expression in the frontal cortex and olfactory bulb compared to control. Nicotine vapour significantly increased DRD2 expression only in the olfactory cortex. NS oil administration reduced both the cigarette-smoke-induced increase in α4-nAChR and nicotine vapour-induced increase in DRD2 gene expression only in the olfactory cortex. CONCLUSION: Findings from this study suggest that NS oil improves brain antioxidant status while ameliorating nicotine vapour and cigarette smoke addiction through down-regulation of α4-nAChR and DRD2 gene expressions in discrete brain regions in Sprague-Dawley rats.
Assuntos
Antioxidantes , Encéfalo , Carum , Nicotina , Óleos de Plantas , Ratos Sprague-Dawley , Receptores Nicotínicos , Animais , Masculino , Receptores Nicotínicos/metabolismo , Receptores Nicotínicos/genética , Receptores Nicotínicos/efeitos dos fármacos , Nicotina/farmacologia , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Encéfalo/metabolismo , Encéfalo/efeitos dos fármacos , Óleos de Plantas/farmacologia , Ratos , Receptores de Dopamina D2/metabolismo , Receptores de Dopamina D2/genética , Receptores de Dopamina D2/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Fumaça/efeitos adversosRESUMO
BACKGROUND: Abnormal vascular reactivity and reduced expression of endothelial nitric oxide synthase (eNOS) gene are hallmark of salt-induced hypertension in rats. Although l-arginine is an established vasodilator, the mechanism by which it modulates vascular reactivity in salt-induced hypertension is not clearly understood. OBJECTIVES: This study was designed to investigate the mechanism by which oral l-arginine supplementation modulates vascular reactivity and eNOS gene expression in Sprague-Dawley rats fed a high-salt diet. METHODS: Forty-eight weaned male Sprague-Dawley rats of weight range 90 to 110 g were randomly divided into 6 groups of 8 rats per group. Group I was fed normal rat chow ad libitum and served as the Normal Diet group. Group II was fed a diet that contained 8% NaCl. Groups III and IV took normal and high-salt diet, respectively, and then received oral l-arginine supplementation (100 mg/kg/day), while groups V and VI took normal and high-salt diet, respectively, and then were co-administered with both l-arginine and l-nitro-arginine methyl ester (L-NAME; 100 mg/kg/day and 40 mg/kg/day, respectively) orally. At the end of 12-week experimental period, the animals were sacrificed to assess vascular reactivity and gene expression level. RESULTS: Our results show that high-salt diet significantly reduced (P < .05) endothelium-dependent relaxation response to acetylcholine and qualitatively reduced eNOS gene expression in the abdominal aorta of the rats. However, l-arginine supplementation improved the impaired endothelium-dependent relaxation and nitric oxide level while ameliorating the reduced eNOS gene expressions. CONCLUSION: This study suggests that oral supplementation of l-arginine enhances endothelial-dependent relaxation in rats fed a high-salt diet by ameliorating eNOS gene expression in the abdominal aorta of the rats.
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BACKGROUND: Cisplatin is an anti-cancer drug that causes nephrotoxicity and oxidative stress. Extracts of Nigella sativa is nephroprotective. Vitamin E is also a potent antioxidant. This study sought to determine a possible synergistic effect of administering the two agents prior to cisplatin use on nephrotoxicity and oxidative stress. METHODS: 48 male Wistar rats were randomly divided into 6 groups of 8 rats each. Group I served as the control. Group II received cisplatin without any treatment for 6 days. Groups III, IV, V and VI received 100 mg/kg Nigella sativa (NS), 200 mg/kg NS, 100 mg/kg Vitamin E and 200 mg/kg NS+100 mg/kg Vitamin E respectively for 5 days prior to 6 days administration of cisplatin. On the last day of the experiment, all the animals were sacrificed and serum samples collected for analysis. RESULTS: Cisplatin administration caused a significant increase in creatinine level (p<0.01), urea level (p<0.01), sodium concentration and malondialdehyde level (p<0.001). Pre-administration with NS caused a significant reduction in creatinine level (p<0.001), urea level (p<0.001), sodium concentration (p<0.001) and malondialdehyde (p<0.01) level. Pre-administration with vitamin E caused a significant reduction in creatinine level (p<0.001), urea level (p<0.01), sodium concentration (p<0.001) and malondialdehyde level. They both also caused a significant increase in superoxide dismutase, reduced glutathione and catalase (CAT) levels. The combination of NS and vitamin E however did not show significant synergistic effects. CONCLUSION: These results suggest that even though pre-administration of the two agents protect against renal toxicity and oxidative stress, the effects are however not collaborative.
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Cisplatino/efeitos adversos , Nefropatias/prevenção & controle , Nigella sativa/química , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Vitamina E/administração & dosagem , Animais , Catalase/sangue , Creatinina/sangue , Modelos Animais de Doenças , Humanos , Rim/efeitos dos fármacos , Rim/metabolismo , Nefropatias/sangue , Nefropatias/induzido quimicamente , Masculino , Malondialdeído/sangue , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Substâncias Protetoras/uso terapêutico , Distribuição Aleatória , Ratos , Ratos Wistar , Superóxido Dismutase/sangue , Ureia/sangueRESUMO
OBJECTIVE: Anacardium occidentale L. leaf is useful in the treatment of inflammation and asthma, but the bioactive constituents responsible for these activities have not been characterized. Therefore, this study was aimed at identifying the bioactive constituent(s) of A. occidentale ethanolic leaf extract (AOEL) and its solvent-soluble portions, and evaluating their effects on histamine-induced paw edema and bronchoconstriction. METHODS: The bronchodilatory effect was determined by measuring the percentage protection provided by plant extracts in the histamine-induced bronchoconstriction model in guinea pigs. The anti-inflammatory effect of the extracts on histamine-induced paw edema in rats was determined by measuring the increase in paw diameter, after which the percent edema inhibition was calculated. The extracts were analyzed using gas chromatography-mass spectrometry to identify the bioactive constituents. Column chromatography and Fourier transform infrared spectroscopy were used respectively to isolate and characterize the constituents. The bronchodilatory and anti-inflammatory activities of the isolated bioactive constituent were evaluated. RESULTS: Histamine induced bronchoconstriction in the guinea pigs and edema in the rat paw. AOEL, hexane-soluble portion of AOEL, ethyl acetate-soluble portion of AOEL, and chloroform-soluble portion of AOEL significantly increased bronchodilatory and anti-inflammatory activities (Pâ¯<â¯0.05). Oleamide (9-octadecenamide) was identified as the most abundant compound in the extracts and was isolated. Oleamide significantly increased bronchodilatory and anti-inflammatory activities by 32.97% and 98.41%, respectively (Pâ¯<â¯0.05). CONCLUSION: These results indicate that oleamide is one of the bioactive constituents responsible for the bronchodilatory and anti-inflammatory activity of A. occidentale leaf, and can therefore be employed in the management of bronchoconstriction and inflammation.