The protective effects of gallic acid and SGK1 inhibitor on cardiac damage and genes involved in Ca2+ homeostasis in an isolated heart model of ischemia/reperfusion injury in rat.

Serum and glucocorticoid-induced kinase 1 (SGK1) is an enzyme that may play a vital role in myocardial ischemia/reperfusion (I/R) injury. This enzyme may affect sarcoplasmic reticulum Ca2+ ATPase (SERCA2), ryanodine receptor (RyR2) and sodium/calcium exchanger (NCX1) during myocardial ischemia/reperfusion injury. The objective of this investigation was to analyze the effects of the combination of GSK650394 (SGK1 inhibitor) and gallic acid on the calcium ions regulation, inflammation, and cardiac dysfunction resulting from ischemia/reperfusion (I/R) injury in the heart. Sixty male Wistar rats were randomly divided into six groups, pretreated with gallic acid or vehicle for 10 days. Then the heart was isolated and exposed to I/R. In the SGK1 inhibitor groups, GSK650394 was infused 5 min before ischemia induction. After that, Ca2+ homeostasis, inflammatory factors, cardiac function, antioxidant activity, and myocardial damage were evaluated. The findings suggested that the use of two drugs in combination therapy produced more significant improvements in left ventricular end diastolic pressure, left ventricular systolic pressure, RR-interval, ST-elevation, inflammation factors, and antioxidant enzymes activity as compared to the use of each drug. Despite this, there was a significant decrease observed in heart marker enzymes (including lactate dehydrogenase (LDH), troponin-I (cTn-I), creatine kinase-MB (CK-MB) and creatine phosphokinase (CPK) when compared to the ischemic group. Additionally, the expression of RyR2, NCX1, and SERCA2 genes showed a noteworthy increase as compared to the ischemic group. The findings of this study propose that using both of these agents on myocardial I/R injury could have superior advantages compared to using only one of them.

Effect of Gallic Acid Pretreatment and SGK1 Enzyme Inhibition on Cardiac Function and Inflammation in a Rat Model of Ischemia-Reperfusion Injury.

Background: Serum and glucocorticoid-induced kinase 1 (SGK1) is an enzyme that may play an important role in ischemic-reperfusion (I/R) injury and myocardial dysfunction. Although many studies have been conducted on individual antioxidants, little attention has been paid to the effects of co-administration of an antioxidant with an SGK1 inhibitor on cardiac function after I/R. Methods: This study aimed to determine the effects of gallic acid (as an antioxidant) combined with an SGK1 inhibitor on I/R-induced cardiac dysfunction and inflammation. Sixty male Wistar rats were randomized into 6 groups, pretreated with gallic acid or vehicle for 10 days. Subsequently, the heart was isolated and exposed to I/R. In groups that received the SGK1 inhibitor, the heart was perfused with the SGK1 inhibitor GSK650394, 5 min before induction of ischemia. After that, cardiac function, inflammatory factors, and myocardial damage were evaluated. Results: The combination of these two compounds improved cardiac contractility, heart rate, rate pressure product, left ventricular developed pressure, left ventricular systolic pressure, perfusion pressure, and QRS voltage significantly (P < 0.05). In addition, concomitant therapy of these two agents reduced tumor necrosis factor-alpha and interleukin-6, and the activity of creatine kinase-MB, lactate dehydrogenase, and troponin-I (P < 0.05). Conclusion: The results indicated that administration of gallic acid with the SGK1 inhibitor may have a potentiating effect on the improvement of cardiac dysfunction and I/R-induced inflammation.

Protective effects of gallic acid and SGK1 inhibitor on oxidative stress and cardiac damage in an isolated heart model of ischemia/reperfusion injury in rats.

Objectives: Oxidative stress and serum and glucocorticoid-induced Kinase 1 gene (SGK1) perform a central role in the consequences of ischemia in the heart. This research aimed to investigate the effect of coadministration of gallic acid and the GSK650394 (as SGK1 gene inhibitor) on the ischemic complications of a rat model of cardiac ischemia/reperfusion (I/R) injury. Materials and Methods: Sixty male Wistar rats were divided into 6 groups with or without pretreatment with gallic acid for 10 days. After that, the heart was isolated and perfused with Krebs-Henseleit solution. A 30 min of ischemia was performed followed by a 60 min reperfusion. In 2 groups, GSK650394 was infused 5 min before ischemia induction. Ten minutes after reperfusion commencement, cardiac marker enzyme (CK-MB, LDH, and cTn-I) activities were measured in the cardiac perfusate. At the end of reperfusion, the activity of anti-oxidant enzymes (Catalase, Superoxide dismutase, and Glutathione peroxidase), lipid peroxidation (MDA), total anti-oxidant capacity (TAC), intracellular reactive oxygen species (ROS), infarct size, and SGK1 gene expression were measured in the heart tissue. Results: The results indicated that dual therapy with both drugs significantly improved endogenous anti-oxidant enzyme activity and TAC more than each drug alone. However, the heart marker enzymes (CK-MB, LDH, and cTn-I), MDA, ROS, infarct size, and SGK1 gene expression were reduced significantly compared with the ischemic group. Conclusion: The results of this study suggest that concomitant administration of both drugs in the case of cardiac I/R injury may have a more beneficial effect than each one alone.

Natural lavender oil (Lavandula angustifolia) exerts cardioprotective effects against myocardial infarction by targeting inflammation and oxidative stress.

BACKGROUND: The study was conducted to examine therapeutic effects of lavender oil (LO) against myocardial infarction (MI) and its potential mechanisms. METHODS: A rat model of MI was established and LO (100, 200 and 300 mg/kg) was intraperitoneally administrated immediately after ischemia. Anti-inflammatory and antioxidant activity of LO were evaluated by immunohistochemical assay and measurement of SOD, GSH, and MDA. The myocardial injury markers, apoptotic activity and infarct volume were examined by ELISA, TUNEL and TTC staining, respectively. RESULTS: Compared with the control I/R-Vehicle, the expression of tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) significantly reduced 8 h after reperfusion and expression of interleukin-10 (IL-10) elevated 48 h after reperfusion in LO-treated rats (P < 0.05). Likewise, significant decreases in apoptotic activity, infarct volume and significant restoration of antioxidant endogenous defenses were observed in LO-treated rats (P < 0.05). CONCLUSION: Collectively, these findings confirm that LO can be a good candidate to reduce injury after MI.

Berberine confers neuroprotection in coping with focal cerebral ischemia by targeting inflammatory cytokines.

SCOPE: Existing research indicates that anti-inflammatory and antioxidant properties of berberine play major roles in coping with oxidative stress in neurodegenerative diseases, but it is not known if this isoquinoline alkaloid affects inflammatory cytokines such as interleukin 10 in focal cerebral ischemia. METHODS AND RESULTS: Male Wistar rats (10 weeks old) were treated with 40mg/kg concentration of berberine 1h after focal cerebral ischemia and the anti-inflammatory properties of berberine were evaluated by immunohistochemical analysis, water content measure and behavioral tests. Evaluation of infarct volume was performed by TTC staining. Immunohistochemistry and behavioral assessment indicated recovery in treatment group compared to only ischemia group. The infarct volume decreased in treatment group compared to ischemia group. Berberine administration significantly decreased brain edema and contributed to the restoration of motor function. Moreover, berberine potently contributed to neuroprotection in motor area through downregulation of pro-inflammatory cytokines and upregulation of anti-inflammatory cytokines. CONCLUSIONS: These findings confirm the validity of berberine as a potent anti-inflammatory agent in treatment of ischemic stroke.

Effects of Nanoparticles on the Environment and Outdoor Workplaces.

Today, most parts of different nanotechnologies are growing and developing without any special rules and regulations. This could result in undesirable changes in the environment and affect workers in indoor and outdoor workplaces. Carbon-based nanoparticles, such as fullerenes, nanotubes, the oxides of metals such as iron and titanium, and natural inorganic compounds, including asbestos and quartz, can have biological effects on the environment and human health. The risk assessment of such nanoparticles requires evaluation of their mobility, reactivity, environmental toxicity, and stability. With the increasing use of nanoparticles for commercial and industrial purposes, the debate becomes whether the numerous benefits of nanoparticles can overcome the economic costs, environmental impacts, and unknown risks resulting from their use. To date, few studies have been conducted on the toxic and environmental effects that result from direct and indirect exposure to nanoparticles, and there are no clear standards to determine their effects. Lack of technical information in this regard has provided an appropriate context for supporters and opponents of nanoparticles to present contradictory and ill-considered results. Such an uncertain atmosphere has caused increased concerns about the effects of nanoparticles. Therefore, adequate studies to determine the exact, real risks of the use of nanoparticles are required. The information resulting from these studies can be useful in minimizing the environmental hazards that could arise from the use of nanoparticles. Thus, this paper briefly explains the classification of environmental nanoparticles and how to deal with their formation, diffusion, environmental fate and impacts, and our exposure to them.