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This study shows the possible contribution of muscarinic receptors in the pathophysiology of post-traumatic stress disorder. Sprague-Dawley rats of both sexes were exposed to dirty cat litter (trauma) for 10 min and the protocol was repeated 1 week later with a trauma reminder (clean litter). The rats also received intraperitoneal fluoxetine (2.5, 5 or 10 mg/kg/day), propranolol (10 mg/kg/day) or saline for 7 days between two exposure sessions. Functional behavioral experiments were performed using elevated plus maze, following exposure to trauma reminder. Western blot analyses for M-1, M-2, M-3, M-4 and M-5 receptor proteins were employed in the homogenates of the hippocampus, the frontal cortex and the amygdaloid complex. The anxiety indices increased from 0.63 +/- 0.02 to 0.89 +/- 0.04 in rats exposed to the trauma reminder. The freezing times were also recorded as 47 +/- 6 and 133 +/- 12 s, in control and test animals respectively. Fluoxetine or propranolol treatments restored the increases in the anxiety indices and the freezing times. Female rats had higher anxiety indices compared to males. Western blot data showed increases in M-2 and M-5 expression in the frontal cortex. Expression of M-1 receptors increased and M-4 subtype decreased in the hippocampus. In the amygdaloid complex of rats, we also detected a down-regulation of M-4 receptors. Fluoxetine and propranolol only corrected the changes occurred in the frontal cortex. These results may imply that muscarinic receptors are involved in this experimental model of post-traumatic stress disorder. (C) 2012 Elsevier B.V. All rights reserved.

BACKGROUND/AIMS The aim of this study was to investigate the effects of Nigella sativa (NS) oil form on reducing the damage caused by indomethacin in the stomach and duodenum of rats owing to their antioxidant and anti-inflammatory properties. MATERIAL and METHODS The rats were divided into 4 groups: group 1, saline-treated control group; group 2, NS-treated control group; group 3, saline-treated ulcer group and ulcers caused by indomethacin (30 mg/kg) and administration of physiological serum; group 4, NS-treated ulcer group, which is the group receiving NS oil after administration of indomethacin. At the end of the study, blood samples collected from animals were examined for tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and glutathione (GSH), malondialdehyde (MDA) levels and myeloperoxidase (MPO),and Na+/K+-ATPase activities in gastric and intestinal tissue samples. RESULTS Levels of TNF-alpha and IL-1 beta in serum and MDA and MPO values in tissue were found to be higher in the saline-treated ulcer group than in the saline-treated control group. In addition, tissue GSH and Na+/K+-ATPase levels were found to be lower. These values were found to be reversed when comparing NS-treated ulcer group to saline-treated ulcer group. Histopathological findings showed epithelial regeneration and improvement instead of dense tissue damage. CONCLUSION The strong antioxidant and anti-inflammatory effects of NS against potential small intestine and gastric damage were shown using an experimental indomethacin-induced ulcer model in rats. Hence, our study suggests that NS used together with indomethacin can prevent gastrointestinal damage; thus, this agent can create a new clinical therapeutic principle.

Methotrexate (MTX) is an effective cytotoxic agent which is used to treat malignancies and inflammatory diseases. Origanum onites (O. onites) is found throughout the Eastern Mediterranean region and has been used in traditional medicine. The essential oils (EOs) of O. onites rich in highly bioactive phytochemicals such as carvacrol (CVR) and has antiviral, antioxidant, anticancer and proapoptotic properties. The aim of this study was to investigate the protective effects of CVR and O. onites-EO treatment in MTX-induced hepatorenal toxic rats' liver and kidney tissues. The bcl-2/bax ratio, glutathione (GSH) level, malondialdehyde (MDA) level, and myeloperoxidase (MPO) activity of liver and kidney tissues were evaluated in the MTX-induced rat model. Results showed that the administration of CVR or O. onites-EO significantly increased bcl-2/bax expression and GSH levels as well as reduced MDA level and MPO activity in the kidney and liver tissues of MTX-induced rat model. In conclusion, our results suggest that O. onites-EO and CVR have protective effect in MTX-induced hepatorenal toxic rats' liver and kidney tissues by decreasing oxidative stress and apoptosis.

Objective The present study aims to investigate the therapeutic effects of resveratrol (RES) on isoproterenol (ISO) induced myocardial injury rat model. Methods Catecholamine-induced heart damage was induced by ISO treatment for 30 days. The rats were divided into four groups as follows: the control group received saline, the ISO group received 5.0 mg/kg ISO, the RES group received 10 mg/kg RES, and the ISO-RES group received 10 mg/kg RES and 5 mg/kg ISO treatments for 30 days. Following echocardiographic measurements and body weight recorded, the rats were decapitated. Plasma and cardiac tissue samples obtained by decapitation were analyzed using biochemical, histopathological, molecular and immunohistochemical methods. Results In the ISO group, Na+/K+ ATPase activity and ATP content, GSH, and caveolin-3 levels were low. LDH, CK and lysosomal enzyme activities, MDA level, and MPO activity were found to be high. It was determined that GSH and MDA levels and MPO, Na+/K+ ATPase activity, ATP content caveolin-3 levels changes that arose from ISO treatment were suppressed by RES treatment. Conclusion RES treatment has ameliorated all the functional and biochemical parameters. The results obtained in this study suggest that RES is a promising supplement against catecholamine exposure as it improves antioxidant defense mechanisms in the heart. In the light of above-mentioned data, RES can be assumed as a promising agent in ameliorating the oxidative injury of the myocardium.

BACKGROUND/AIMS Humic acid (HA) formed by the decomposition of organic matter is a high-molecular-weight polymer. Humic-derived substances are potential drugs for human health, and their role in the prevention and treatment of diseases, like diabetes, antiviral, UV-B protective effect, cancer, and cardiovascular disease, is emphasized in various studies. It has antiulcerogenic, antitumor. Yang et al. demonstrated that HA exerts an antiproliferative effect and growth inhibition on HL-60 cells through the induction of apoptosis. A study showed that the antiulcer effect of Shilajit (HAs extracted from Shilajit) samples may be due to antimicrobial, anti-inflammatory, antianxiety, antioxidant, healing, and regenerative effects. The present study aimed to investigate the effects of HA on cultures of the chronic myeloid leukemia cell line in vitro. MATERIAL and METHODS We determined the apoptotic effect of HA in K562 cells by using various molecular methods. For cell viability, HA was tested in vitro against K562 cell lines using the MTT colorimetric process. Bax, bcl-2, casp-3, and casp-9 expressions were quantified by Western blot. Apoptosis analysis has been made with the Annexin-V/PI method. RESULTS The IC50 values of HA were determined 100 mg mL(-1) for the K562 cell line. HA has been shown to inhibit cell proliferation. As the bcl-2/bax ratio decreased and increasing the levels of caspase-3 and caspase-9, the cells underwent apoptosis. CONCLUSION As a result, HA showed the anticancer effect on leukemia cells. In the future, HA can be used as a chemopreventive agent in leukemia treatments.

Objectives: The purpose of this study was to investigate possible protective effects of St. John's wort in the hepatic ischemia/reperfusion injury. Material and Methods: The hepatic artery, portal vein, and bile duct were all clamped for 45 minutes to induce ischemia in rats, and after that reperfusion for 1 hour. SJW was administrated orally, once a day for 3 days before ischemia/reperfusion. The aspartate aminotransferase, alanine aminotransferase, tumor necrosis factor, and interleukin levels were measured in the serum samples. Luminol chemiluminescence, lucigenin luminol chemiluminescence levels; myeloperoxidase. The sodium-potassium ATPase (Na+/K+ ATPase) activity was determined in the liver tissue, and caspase-3 and caspase-9 activity with the bcl-2/bax ratio were measured by the western blot analysis. Results: The St. John's wort administration recovered the aspartate aminotransferase, alanine aminotransferase, tumor necrosis factor, and IL-1 beta levels serum parameters meaningfully, while ischemia/reperfusion caused an increase in luminol chemiluminescence, lucigenin luminol chemiluminescence, myeloperoxidase, caspase-3, and caspase-9 activity and led to a decrease in the B-cell lymphoma-2/bcl-2-associated X protein (bcl-2/bax) ratio and the Na+/K+ ATPase activity. Conclusion: The obtained results indicate protective effects of St. John's wort on the ischemia/reperfusion injury through various mechanisms, and we are able to suggest that St. John's wort can clinically create a new therapeutic principle.

Objective: In the present study, it was aimed to study the antioxidant effects of spironolactone (SPL) to determine its possible protective effects in hepatic ischemia reperfusion injury. Material and Methods: Hepatic artery, portal vein, and bile duct of Wistar albino rats were clamped for 45 minutes under anesthesia to form an ischemia period. Then reperfusion was allowed and the rats were decapitated 60 minutes later. SPL (20 mg/kg, p.o.) or SF was orally administered for 30 minutes before ischemia. Rats in the control arm underwent sham surgery and were administered isotonic saline. Liver function was studied by measuring aspartate aminotransferase (AST), alanine aminotransferase (ALT), tumor necrosis factor-alpha (TNF-alpha), and interleukin 1beta (IL-1 beta) levels. Malondialdehyde (MDA), glutathione (GSH), luminol, and lucigenin levels, myeloperoxidase (MPO) and Na+-K+- ATPase enzyme activities were analyzed to study tissue injury under light microscope. Results: While IR increased AST, ALT, TNF-alpha, and IL-1 beta levels and MDA, luminol, and lusigenin levels and MPO activities, it caused a decrease in GSH levels and Na+K+-ATPase activity. Spironolactone administration significantly improved these values. Conclusion: Protective effects of SPL against ischemia/reperfusion injury via various mechanisms suggest that this agent may become a novel treatment agent in clinical practice.

BACKGROUND: This study was designed to determine possible protective effect of betaine treatment against oxidative injury in pulmonary tissue induced with thermal trauma. METHODS: Under ether anesthesia, shaved dorsum of Wistar albino rats was exposed to a 90 degrees C water bath for 10 seconds to induce burn injury. Betaine was administered orally (250 mg/kg) for a period of 21 days before burn injury, and single dose of betaine was administered after thermal injury. Control group rats were exposed to 25 degrees C water bath for 10 seconds. Upon conclusion of experiment, rats were decapitated and blood was collected for analysis of pro-inflammatory cytokines and lactate dehydrogenase (LDH) activity. Lung tissue samples were taken to determine malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO), and Na+/K+-ATPase activity, in addition to histological analysis. RESULTS: Burn injury caused significant increase in both cytokine levels and LDH activity. In lung samples, raised MDA levels, MPO activity, and reduced GSH levels and Na+/K+-ATPase activity were found due to burn injury. CONCLUSION: Treatment of rats with betaine significantly restored GSH level and Na+/K+-ATPase activity, and decreased MDA level and MPO activity. According to the findings of the present study, betaine significantly diminishes burn-induced damage in tissue.