Agomelatine protects heart and aorta against lipopolysaccharide-induced cardiovascular toxicity via inhibition of NF-kß phosphorylation.

The aim of this study was to investigate the possible ameliorating effects of agomelatine (AGO) on lipopolysaccharide (LPS)-induced endothelial and cardiac damage. Twenty-four female Wistar Albino rats divided into 3 groups as follows: Control, LPS and LPS + AGO. Total oxidant status (TOS), total antioxidant status (TAS), nuclear factor kappa beta (NF-kß)/p65, p-NF-kß, full caspase-8 (Cas-8) and cleaved cas-8 levels were measured in cardiac tissues and creatine kinase MB (CKMB), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) levels in blood biochemically. In addition; cas-8, sirtuin-1 (SIRT-1), interleukin-4 (IL-4), interleukin-10 (IL-10), haptoglobin measured histopathologically in cardiac and aortic tissues. The levels of CKMB, AST, LDH and TOS were increased and TAS were decreased in the LPS group. In Western blot analyses NF-kß/p65, p-NF-kß/p65, full and cleaved cas-8 protein levels increased in cardiac tissues of LPS group. In histopathological and immunohistochemical evaluation of the heart sections; hyperemia, micro-hemorrhages and inflammatory cell infiltrations, increase of cas-8, haptoglobin, IL-4 and IL-10 and decrease of SIRT-1 levels were observed in cardiac and endothelial tissues of LPS groups. AGO treatment reversed all these parameters. It was shown that LPS-induced inflammation, oxidative stress and apoptosis via increasing of NF-kß/p65 signaling, decreasing of SIRT-1 levels and increase of cas-8 levels in heart and endothelial tissues respectively. AGO corrected all these parameters by its antioxidant, antiinflammatory and antiapoptotic activities.

Ameliorative effects of pregabalin on LPS induced endothelial and cardiac toxicity.

We investigated the antioxidant, anti-inflammatory and anti-apoptotic effects of pregabalin (PREG) on lipopolysaccharide (LPS) induced sepsis related cardiotoxicity via NF-kß pathways. We used 24 female Wistar albino rats divided into three groups: control, LPS treated and LPS + PREG treated. Total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), tumor necrosis factor alpha (TNF-α), nuclear factor kappa beta (NF-kß)/p65, p-NF-kß/p65, caspase-3 (Cas-3) and cleaved Cas-3 were measured in cardiac tissues and creatine kinase MB (CKMB), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) levels were measured in blood samples. Also, Cas-3, granulocyte-colony stimulating factors (G-CSF), interleukin-6 (IL-6), serum amyloid A (SAA) and inducible nitric oxide synthase (iNOS) were measured immunohistochemically in heart and aorta tissue. In the LPS group; the levels of CKMB, AST, LDH, TOS, OSI increased and TAS decreased. TNF-α, p-NF-kß/p65 and Cas-3 protein levels also increased in the LPS group. Immunohistochemical evaluation of the heart and aorta revealed a significant increase in the levels of Cas-3, G-CSF, SAA, IL-6 and iNOS in the LPS group. PREG treatment restored all measurements to near normal. LPS induced cardiovascular toxicity was due to inflammation, oxidative stress and apoptosis. PREG ameliorated the damage by inhibition of NF-kß phosphorylation.

Misoprostol ameliorates doxorubicin induced cardiac damage by decreasing oxidative stress and apoptosis in rats.

We investigated the potential cardioprotective effects of misoprostol (MP) on doxorubicin (DOX) induced cardiac damage using histologic and biochemical assessment of rat heart. We used 21 male rats divided randomly into three groups: group 1, control; group 2, DOX; group 3, DOX + MP. The control group was given 0.5 ml 0.9% NaCl intraperitoneally (i.p.) and 1 ml 0.9% NaCl orally for 6 days. DOX was administered as a single dose of 20 mg/kg i.p. on day 3. MP was administered orally for 6 days. We found that treatment with MP decreased significantly serum cardiac troponin-I, brain natriuretic peptide levels, and lactate dehydrogenase, aspartate aminotransferase, alanine transaminase and creatine kinase isoenzyme-MB activities. DOX increased the malondialdehyde level and decreased the catalase, superoxide dismutase activities and glutathione levels; MP prevented these alterations. MP also decreased NADPH oxidase-4 and caspase-3 levels. In the DOX + MP group, oxidative stress was decreased, antioxidant activity was increased and histopathological changes were decreased compared to the DOX group. Cardiac damage caused by DOX was attenuated by MP treatment owing to the antioxidative and anti-apoptotic effects of MP. MP may be useful for reducing the severity of DOX induced damage.

Melatonin protects the heart and endothelium against high fructose corn syrup consumption-induced cardiovascular toxicity via SIRT-1 signaling.

High fructose corn syrup (HFCS) has been shown to cause cardiovascular toxicity via oxidative stress and inflammation. The aim of this study is to demonstrate the protective effects of melatonin (MLT) against HFCS-induced endothelial and cardiac dysfunction via oxidative stress and inflammation. Thirty-two Sprague Dawley male rats were distributed into three groups as control, HFCS, and HFCS + MLT. HFCS form F55 was prepared as 20% fructose syrup solution and given to the rats through drinking water for 10 weeks, and MLT administrated 10 mg/kg/day orally for last 6 weeks in addition to F55. After decapitation, blood and half of the heart samples were collected for biochemical analysis and other half of the tissues for histopathological and immunohistochemical analysis. Aspartate transaminase, creatine kinase MB, lactate dehydrogenase, total oxidant status and oxidative stress index, and caspase-3 levels increased and total antioxidant status levels decreased significantly in HFCS group. MLT treatment reversed all these parameters. Histopathologically, hyperemia, endothelial cell damage and increased levels of angiogenin, C-reactive protein, inducible nitric oxide synthase, myeloperoxidase and decreased sirtuin-1 (SIRT-1) expressions were observed in HFCS group. MLT ameliorated all these changes. MLT has an anti-inflammatory, antioxidant, antiapoptotic effects on HFCS-induced cardiovascular toxicity through enhancing the expression of SIRT-1.

Anti-inflammatory and antiresorptive functions of melatonin on experimentally induced periapical lesions.

AIM: To investigate the effects of systemically administered melatonin on inflammation and alveolar bone resorption in rats with experimentally induced periapical lesions. METHODOLOGY: Thirty adult Sprague Dawley rats were divided equally into negative, positive control and melatonin groups. The pulp chambers of their mandibular first molars were exposed to the oral environment to induce experimental periapical lesions in the positive control and melatonin groups. The melatonin group received daily intraperitoneal injections of melatonin at a dose of 10 mg kg-1 . After 21 days, the animals were euthanized; the hemi-mandible parts were prepared for radiological, histopathological, immunohistochemical (IL-1ß, RANK, RANKL, OPG and tartrate-resistant acid phosphatase (TRAP) and Brown-Brenn (bacteria) evaluations. Data were analysed by Kruskal-Wallis (for non-parametric data) and one-way anova tests (for parametric data) (P < 0.05). RESULTS: The area of radiographic periapical bone loss was significantly smaller in rats that were given daily intraperitoneal injections of melatonin (P < 0.01). The histopathological scores of the melatonin group were significantly lower than those of positive control group (P < 0.01). Histomorphometrically, the area of periapical bone loss in the melatonin group was significantly smaller than the positive control group (P < 0.01). The expression of IL1-ß, RANK and RANKL was significantly higher in the positive control group, whereas OPG was significantly higher in the melatonin group (P < 0.01). The number of osteoclasts was significantly greater in the positive control group by TRAP staining analyses (P < 0.01). The scores for bacteria localization using Brown-Brenn staining in the melatonin group was significantly lower than that of the positive control group (P < 0.01). CONCLUSIONS: Melatonin demonstrated antiresorptive effects on bone associated with experimentally induced periapical lesions in rats via its anti-inflammatory activity. Further studies are necessary to evaluate its possible effects on the healing of periapical lesions.

The impact of electric fields on testis physiopathology, sperm parameters and DNA integrity-The role of resveratrol.

This study investigated the long-term effects of electric fields (EF) which might cause physiopathological or morphological changes in the testis tissues of rats. We assumed that using resveratrol (RES) might reduce harmful effects of the EF. Thirty-two male Wistar Albino rats were randomly divided into four groups with eight animals in each; control, EF, EF + RES and RES. Malondialdehyde (MDA), superoxide dismutase, catalase, glutathione peroxidase and histopathological parameters were evaluated in testis tissue. Epididymal sperm count, motility and DNA damage were studied. Total testosterone, follicle-stimulating hormone, luteinising hormone, estradiol and growth hormone levels were evaluated in the plasma samples. EF caused statistically significant increase in MDA levels, body weight and DNA damage. A significant decrease was detected in sperm count and motility. The histopathological examination of the testes showed the germ cell decrease in the seminiferous epithelium with oedema and vascular congestion in the interstitial tissue. In immunohistochemical examination, the increase in the apoptotic cells number was detected. RES partially ameliorated biochemical, histopathological and immunohistochemical findings in the EF + RES group. These findings clearly demonstrated that EF can cause damage in rat testis. RES can ameliorate the damage caused by EF.

A RARE CAUSE OF PITUITARY APOPLEXY: CABERGOLINE THERAPY.

Pituitary apoplexy (PA) is a life-threatening clinical syndrome. Dopamine receptor agonists are the drugs of choice in the treatment of prolactinomas. The use of cabergoline is reported to cause an increased risk of PA, particularly in macroprolactinomas of cystic nature. In this report, we present a patient with a cystic macroprolactinoma who developed PA on the 16th week of cabergoline treatment.

Vitamin C attenuates methotrexate-induced oxidative stress in kidney and liver of rats.

Like several other anticancer drugs, methotrexate (MTX) causes side effects, such as neuropathic pain, hepatotoxicity, and nephrotoxicity. Abnormal production of reactive oxygen species has been suspected in the pathophysiology of MTX-induced hepatorenal toxicity. Therefore, the aim of this study was to investigate the probable protective role of vitamin C (Vit C) on oxidative stress induced by MTX in the liver and kidney tissues of rats. A total of 32 rats were randomly and equally divided into four groups. The first group served as the control group. The second group received a single dose of 20 mg/kg of MTX intraperitoneally. To demonstrate our hypothesis, the third and the fourth groups received 250 mg/kg of Vit C for 3 days by oral gavage, with or without MTX treatment. At the end of the study, the liver and kidney tissues of the rats were collected and examined using histology. Both the tissues were assayed for malondialdehyde concentration and superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities. In hepatic and renal tissues, lipid peroxidation levels were increased, whereas SOD, CAT, and GSH-Px levels were decreased by MTX. All parameters, including CAT levels in hepatic tissue, were significantly restored after the administration of Vit C for 3 days. Similar to the biochemical findings, evidence of oxidative damage was examined in both types of tissues by histopathological examination. From the results of this study, we were able to observe that Vit C administration modulates the antioxidant redox system and reduces the renal and hepatic oxidative stress induced by MTX. Vit C can ameliorate the toxic effect of MTX in liver and kidney tissues of rat.

The effects of electromagnetic radiation (2450 MHz wireless devices) on the heart and blood tissue: role of melatonin.

OBJECTIVE: This study was designed to investigate the effects of 2450 MHz EMR on the heart and blood in rat and possible ameliorating effects of melatonin. MATERIAL AND METHOD: Thirty-two female Wistar Albino rats were randomly grouped (by eight in each group) as follows:  Group I: cage-control group (dimethysulfoxide (DMSO), 10mg/kg/day i.p. without stress and EMR. Group II: sham-control rats stayed in restrainer without EMR and DMSO (10mg/kg/day i.p.). Group III: rats exposed to 2450 MHz EMR. Group IV: treated group rats exposed to 2450 MHz EMR+melatonin (MLT) (10mg/kg/day i.p.). RESULTS: In the blood tissue, there was no significant difference between the groups in respect of erythrocytes GSH, GSH-Px activity, plasma LP level and vitamin A concentration (p > 0.05). However, in the Group IV, erythrocytes' LP levels (p < 0.05) were observed to be significantly decreased while plasma vitamin C, and vitamin E concentrations (p < 0.05) were found to be increased when compared to Group III. In the heart tissues, MDA and NO levels significantly increased in group III compared with groups I and II (p < 0.05). Contrary to these oxidant levels, CAT and SOD enzyme activities decreased significantly in group III compared with groups I and II (p 0.05). Besides, MLT treatment lowered the MDA and NO levels compared with group III. DISCUSSION: In conclusion, these results demonstrated that contrary to its effect on the heart, the wireless (2450 MHz) devices cause slight oxidative-antioxidative changes in the blood of rats, and a moderate melatonin supplementation may play an important role in the antioxidant system (plasma vitamin C and vitamin E). However, further investigations are required to clarify the mechanism of action of the applied 2450 MHz EMR exposure (Tab. 3, Fig. 1, Ref. 49).

The impact of high fructose on cardiovascular system: Role of α-lipoic acid.

The aim of this study was to evaluate the role of α-lipoic acid (α-LA) on oxidative damage and inflammation that occur in endothelium of aorta and heart while constant consumption of high-fructose corn syrup (HFCS). The rats were randomly divided into three groups with each group containing eight rats. The groups include HFCS, HFCS + α-LA treatment, and control. HFCS was given to the rats at a ratio of 30% of F30 corn syrup in drinking water for 10 weeks. α-LA treatment was given to the rats at a dose of 100 mg/kg/day orally for the last 6 weeks. At the end of the experiment, the rats were killed by cervical dislocation. The blood samples were collected for biochemical studies, and the aortic and cardiac tissues were collected for evaluation of oxidant-antioxidant system, tissue bath, and pathological examination. HFCS had increased the levels of malondialdehyde, creatine kinase MB, lactate dehydrogenase, and uric acid and showed significant structural changes in the heart of the rats by histopathology. Those changes were improved by α-LA treatment as it was found in this treatment group. Immunohistochemical expressions of tumor necrosis factor α and inducible nitric oxide synthase were increased in HFCS group, and these receptor levels were decreased by α-LA treatment. All the tissue bath studies supported these findings. Chronic consumption of HFCS caused several problems like cardiac and endothelial injury of aorta by hyperuricemia and induced oxidative stress and inflammation. α-LA treatment reduced uric acid levels, oxidative stress, and corrected vascular responses. α-LA can be added to cardiac drugs due to its cardiovascular protective effects against the cardiovascular diseases.