The effects of dexmedetomidine on trauma-induced secondary injury in rat brain.

BACKGROUND: The objective of this study was to investigate the effect of dexmedetomidine (Dex), a sedative drug with little or no depressant effect on respiratory centers, on secondary injury in rat brain tissue by means of the Na+/K+ ATPase enzyme, which maintains the cell membrane ion gradient; malondialdehyde, an indicator of membrane lipid peroxidation; glutathione, an indicator of antioxidant capacity; and histopathological analyses. METHODS: Eighteen rats were randomized into three groups: the trauma group received anesthesia, followed by head trauma with a Mild Traumatic Brain Injury Apparatus; the Trauma+Dex group received an additional treatment of 100 µg/kg intraperitoneal dexmedetomidine daily for three days; the Control group received anesthesia only. RESULTS: The highest MDA levels compared to the Control group were found in the Trauma group. Mean levels in the Trauma+Dex group were lower, albeit still significantly high compared to the Control group. Glutathione levels were similar in all groups. Na/K-ATPase levels were significantly lower in the Trauma group compared to both the Control group and the Trauma+Dex group. Histopathologic findings of tissue degeneration including edema, vascular congestion and neuronal injury, and cleaved caspase-3 levels were lower in the Trauma+Dex group compared with the Trauma group. CONCLUSIONS: Dexmedetomidine administered during the early stage of traumatic brain injury may inhibit caspase-3 cleavageHowever, the mechanism does not seem to be related to the improvement of MDA or GSH levels.

The Effects of White Tea (Camellia Sinensis) and Infliximab Against Cisplatin- Induced Testicular Damage via Oxidative Stress and Apoptosis / Efectos del Té Blanco (Camellia Sinensis) e Infliximab Contra el Daño Testicular Inducido por Cisplatino a Través del Estrés Oxidativo y la Apoptosis

SUMMARY: Cisplatin (Cis) is an important chemotherapeutic agent used in cancer treatment. Males exposed to Cis were reported to exhibit testicular toxicity. Cis-induced testicular toxicity is mediated by oxidative stress, inflammation, testosterone inhibition and apoptosis. Accordingly, this study was conducted to evaluate the potential protective roles of infliximab (IFX), which is an anti- TNF-a agent, and of white tea (Camellia sinensis), which is known to possess antioxidant, anti-apoptotic, and anti-inflammatory effects, against Cis-induced testicular toxicity in rats. Rats were randomly assigned into five groups as follows: control group, Cisplatin (7 mg/kg) treatment group, Cisplatin (7 mg/kg) + infliximab (7 mg/kg) treatment group, cisplatin + white tea (WT) treatment group, and Cisplatin+ WT+IFX combined treatment group. In the present study, Cis exposure reduced the sperm count. It also increased testicular oxidative stress as well as the levels of inflammatory and apoptotic markers. Histopathological assays supported the biochemical findings. Treatment with IFX and/or WT restored testicular histology, preserved spermatogenesis, suppressed oxidative stress and apoptosis, and significantly ameliorated Cis-induced damage. It was concluded that white tea and infliximab could potentially serve as therapeutic options for the protection of testicular tissue against the harmful effects of Cis.

El cisplatino (Cis) es un importante agente quimioterapéutico utilizado en el tratamiento del cáncer. Se informó que los hombres expuestos a Cis exhibieron toxicidad testicular. La toxicidad testicular inducida por Cis está mediada por el estrés oxidativo, la inflamación, la inhibición de la testosterona y la apoptosis. En consecuencia, este estudio se realizó para evaluar las posibles funciones protectoras de infliximab (IFX), un agente anti-TNF-α, y del té blanco (Camellia sinensis), conocido por sus propiedades antioxidantes, antiapoptóticas y anti-TNF-α -efectos inflamatorios, contra la toxicidad testicular inducida por Cis en ratas. Cinco grupos de ratas se asignaron al azar de la siguiente manera: grupo control, grupo de tratamiento con cisplatino (7 mg/ kg), grupo de tratamiento con cisplatino (7 mg/kg) + infliximab (7 mg/kg), grupo de tratamiento con cisplatino + té blanco (WT), y grupo de tratamiento combinado Cisplatino+ WT+IFX. En el presente estudio, la exposición a Cis redujo el conteo de espermatozoides. También aumentó el estrés oxidativo testicular, así como los niveles de marcadores inflamatorios y apoptóticos. Los ensayos histopatológicos respaldaron los hallazgos bioquímicos. El tratamiento con IFX y/o WT restauró la histología testicular, preservó la espermatogénesis, suprimió el estrés oxidativo y la apoptosis, y mejoró significativamente el daño inducido por Cis. Se concluyó que el té blanco y el infliximab podrían potencialmente servir como opciones terapéuticas para la protección del tejido testicular contra los efectos nocivos de Cis.

Neuroprotective effects of Vaccinium myrtillus on damage-related brain injury.

Traumatic brain injury may trigger the secondary brain injury, which has the potential to be reversible and thus preventable. Anthocyanins are phylotherapeutic plants, which are reported to exhibit anti-inflammatory properties. This study aimed to evaluate the therapeutic efficiency of an anthocyanin, namely Vaccinium myrtillus, to alleviate secondary brain injury and identify possible mechanism of actions. It is hypothesized that lipid peroxidation and Na+ -K+ -ATPase activity may be involved in neuronal ischemia. Thus, brain tissue Malondialdehyde content, Na+ -K+ -ATPase content, and cleaved caspase-3 content was investigated following moderate head trauma in a rat model. Twenty-four Sprague-Dawley male rats were allocated into four groups: Control, Trauma, Solvent-Control, and Treatment. Trauma and Solvent-Control groups showed more prominent brain edema, neuronal ischemia, vascular congestion, increase in brain tissue Malondialdehyde and cleaved caspase-3 levels, and decreased Na+-K+-ATPase activity compared to the Control group. Although the Treatment group had comparable histological signs to the Trauma and Solvent-Control groups, Malondialdehyde level and Na+-K+-ATPase activity was similar to Control group, and cleaved caspase-3 levels were lower compared to Trauma and Solvent-Control groups. We conclude that anthocyanin extracts may alleviate secondary brain injury via anti-oxidative and anti-apoptotic mechanisms.

Diagnostic value of serum signal peptide-CUB-EGF-like domain-containing protein 1 levels in patients with acute appendicitis

SUMMARY OBJECTIVE: Acute appendicitis is one of the most common surgical causes of an acute abdomen among patients admitted to the emergency room due to abdominal pain. The clinical diagnosis of acute appendicitis is usually difficult and is made by evaluating the clinical, laboratory, and radiological findings together. The aim of this study was to investigate the diagnostic potential of signal peptide-CUB-EGF-like domain-containing protein 1 as a biomarker for acute appendicitis. METHODS: A total of 67 adult patients without any comorbidities who presented to the emergency department with abdominal pain and were clinically diagnosed with acute appendicitis were included in the case group. The patients included in the study were classified into the negative appendectomy group and the acute appendicitis group according to their histopathological final diagnosis. In addition, 48 healthy volunteers without comorbidities were included in the control group. Signal peptide-CUB-EGF-like domain-containing protein 1 levels of patients and the control group were measured. RESULTS: According to postoperative histopathological examinations of the patients, 7 (10.4%) patients were diagnosed with negative appendectomy, and 60 (89.6%) patients were diagnosed with acute appendicitis. Signal peptide-CUB-EGF-like domain-containing protein 1 levels were higher in the patients with acute appendicitis than in negative appendectomy patients (p=0.012). Signal peptide-CUB-EGF-like domain-containing protein 1 levels were also higher in the case group compared to the control group (p=0.001). CONCLUSION: The admission signal peptide-CUB-EGF-like domain-containing protein 1 level was significantly higher in adults with acute appendicitis. The SCUBE1 level is a novel but promising biomarker that aids in the diagnosis of acute appendicitis.

Protective effect of thymoquinone in preventing trauma-related damage: an experimental study.

BACKGROUND: Secondary injury is a potentially modifiable factor of outcome in traumatic brain injury. This study aimed to investigate thymoquinone's effects on trauma-induced neuronal damage. METHODS: Eighteen adult female Sprague-Dawley rats were assigned into three groups following ketamine and xylazine anaesthesia (n = 6): Control, Trauma, Trauma + Thymoquinone. First dose of thymoquinone was administered three hours after the trauma. RESULTS: The trauma group showed significant oedema, vascular congestion, and ischaemia. Also, caspase-3 activity and malondialdehyde content of brain tissue was significantly increased, and Na,K-ATPase activity and glutathione levels were significantly reduced. Thymoquinone significantly reduced oedema, vascular congestion, ischaemia, and caspase-3 activity compared with the trauma group. While Na,K-ATPase activity and glutathione levels was similar to the Control group, malondialdehyde content was similar to the trauma group. CONCLUSIONS: This study showed that low dose thymoquinone exhibited a neuroprotective effect following severe traumatic brain injury, if administered within three hours of injury. Similar levels of glutathione and malondialdehyde suggest no antioxidant effect. Significant reduction in oedema and ischaemia in the neuron cells and partially preserved activity of Na,K-ATPase suggest that thymoquinone protects mitochondrial functions and energy levels of the neuronal cells following severe traumatic brain injury.

Effect of white tea consumption on serum leptin, TNF-α and UCP1 gene expression in ovariectomized rats.

BACKGROUND: Obesity and dyslipidemia due to estrogen deficiency are among the important health problems in menopausal women. Increasing evidence reports the anti-obesity and anti-hyperlipidemic properties of tea polyphenols. However, the effect of white tea (WT) with high polyphenol content on overweight and lipid profile is uncertain. Here, we aimed to examine the effects of long-term WT consumption on serum leptin, tumor necrosis factor- alpha (TNF-α) and uncoupling protein 1 (UCP1) mRNA gene expression in ovariectomized (OVX) rats. METHODS: Adult rats were divided into four groups (n = 8): (i) sham, (ii) OVX, (iii) WT and (iv) OVX + WT. WT was given at a dose of 0.5% w/v for 12 weeks. In the study, body weight, serum leptin, TNF, estradiol (E2) levels, lipid profile and UCP1 mRNA gene expression in brown adipose tissue (BAT) were evaluated. RESULTS: There was a significant increase in body weight of OVX rats, which was decreased following WT consumption. While leptin and E2 levels decreased in the OVX group, TNF levels increased. There was no difference between the NF-kB levels of the groups. In addition, BAT UCP1 mRNA expression was significantly decreased in OVX groups, while WT treatment stimulated UCP1 activity. CONCLUSION: We explain the stimulatory effect of WT on weight loss mainly by the induction of UCP1 gene-mediated thermogenesis and suppression of inflammation. Therefore, we suggest that prolonged WT consumption may have beneficial effects in limiting excess weight gain caused by estrogen deficiency.

The protective effects of angiotensin-converting enzyme inhibitor against cecal ligation and puncture-induced sepsis via oxidative stress and inflammation.

AIMS: Sepsis is a severe public health problem affecting millions of individuals, with global mortality rates caused by lower respiratory tract infections are approximately 2.38 million people a year die from respiratory failure caused by infection. Although ACE is known to contribute to damage in septicemia, the pathophysiological mechanisms of sepsis remain unclear. While mortality can be significantly reduced through effective and sensitive antibiotic therapy, antibiotic resistance restricts the use of these drugs, and the investigation of novel agents and targets is therefore essential. Our aim was to determine whether Perindopril (PER) has anti-inflammatory and antioxidant capable of preventing these adverse conditions resulting in injury in previous studies. MAIN METHODS: Sprague Dawley rats were randomly assigned into the control group, received oral saline solution alone for four days. the cecal ligation and puncture (CLP) group, underwent only cecal ligation and puncture induced sepsis, while the CLP + PER (2 mg/kg) underwent cecal ligation and puncture-induced sepsis together with oral administration of 2 mg/kg PER for four days before induction of sepsis. KEY FINDINGS: Malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), Caspase-3 and nuclear factor kappa B (NF-kß/p65) levels increased in the CLP group. On the other hand, PER (2 mg/kg) oral administration to septic rats decreased MDA, TNF-α and increase glutathione (GSH) in the lung tissue. In addition, PER administration also decreased the lung tissue NF-κB and Caspase-3 immunopositivity against sepsis. SIGNIFICANCE: PER treatment may represent a promising means of preventing sepsis-induced lung injury via antioxidant and anti-inflammation effects.

An investigation of the effects of metformin on ovarian ischemia-reperfusion injury in rats.

Damage to the ovaries or tissue torsion can significantly reduce the ovarian reserve and thus cause severe gynecological and hormonal deficiencies. The discovery of new agents is always needed in the treatment of this condition. Metformin (MET) has been shown to be beneficial in attenuating ovarian ischemia-reperfusion injury. Fifty-six female Sprague Dawley rats were divided into seven groups. Group 1 represented the control group (C), Group 2, the ischemia group (I), and Group 3, the ischemia/reperfusion group (I/R). Group 4, the ischemia (I)+250 group, and Group 5, the ischemia (I)+500 group, received 250 mg/kg and 500 mg/kg MET, respectively. Group 6, the ischemia/reperfusion (I/R)+250 group, and Group 7, the ischemia/reperfusion (I/R)+500 group, received 250 mg/kg and 500 mg/kg MET, respectively. Tissue malondialdehyde (MDA), glutathione (GSH), and tumor necrosis factor-alpha (TNF-α) levels in ovarian tissue increased following I/R, while estradiol (E2) levels decreased. Moreover, infiltration and diffuse edematous areas were observed in addition to diffuse vascular congestion and hemorrhage findings. Caspase-3 and nuclear factor kappa B (NF-κß) expression levels also increased. MDA and TNF-α concentrations decreased in the MET treatment groups, while GSH and E2 levels increased. The findings showed that I/R causes ovarian damage through the induction of oxidative stress, inflammation, and apoptosis. However, MET application was effective in preventing damage in ovarian tissue by reducing levels of reactive oxygen species, proinflammatory cytokines, caspase-3 and NF-κß.

The effect of acute organophosphate intoxication on female rat hippocampus cornu ammonis region pyramidal neuron numbers, biochemistry and morphology.

BACKGROUND: The most commonly used insecticides and pesticides worldwide are organophosphate compounds, chemicals that irreversibly inhibit the cholinesterase enzyme. Acute intoxication with cholinesterase inhibitors is known to cause permanent effects on both the human and rat brains. AIM: To investigate the effect of acute organophosphate intoxication on hippocampus morphology, biochemistry, and pyramidal neuron numbers in female rats. METHODS: Twenty-one rats were randomly divided into three groups. The control group received normal nutrition and underwent no procedures. The sham group received intraperitoneal physiological serum, while the experimental group received intraperitoneal 0.8 g/kg fenthion. Rats were sacrificed 24 h after these procedures. The brains were removed and divided in two halves medially, with one side being kept in 10% neutral formalin. After fixation procedures, tissues were embedded in blocks, sliced, and stained. A neuron count was then performed for the hippocampus. The other hippocampus was homogenized and used for biochemical procedures. RESULTS: Hippocampus sections from rats in the experimental group exhibited swelling and loss of shape in pyramidal cells, while no changes were observed in the control or sham groups. The number of neurons in the experimental group was lower than in the control and sham groups. Biochemical analysis revealed higher MDA and GSH values in the experimental group compared to the control and sham groups. CONCLUSION: Our results show increased apoptotic neurodegeneration of cells in the cornu ammonis region of the hippocampus and changes in biochemical values in rats with acute organophosphate exposure.

An investigation of the effects of N-acetylcysteine on radiotherapy-induced testicular injury in rats.

According to data issued by the International Agency for Research on Cancer in 2012, the estimated number of new cases of all types of cancer worldwide was estimated to exceed 10 million, and 6 million of whom receive radiotherapy. Radiotherapy is the treatment of cancer using ionizing radiation. Our study investigated the effects of x-radiation resulting from radiotherapy (RT) on the testis at the molecular level, and prospectively considered the potential protective characteristics of antioxidants against testicular damage resulting from x-radiation. Forty male Sprague Dawley rats were allocated into five groups, control (group 1), abdominopelvic region 2-Gy-ionizing radiation (group 2), whole-body 6-Gy irradiation (group 3), 2 Gy abdominopelvic region irradiation and 300 mg/kg NAC treatment (group 4), and 6-Gy whole-body irradiation and 300 mg/kg NAC treatment (group 5). Disorganization and vacuolization were observed in the epithelial layer in atrophic seminiferous tubules in the only ionizing radiation (IR) groups. In addition, Johnsen's score decreased in the only IR groups, while testis tissue malondialdehyde (MDA) and glutathione (GSH) tissue levels increased. N-Acetylcysteine (NAC) treatment groups Johnsen's score and tissue GSH levels increased than only IR groups. On the other hand, tissue MDA levels decreased in the NAC treatment groups. The findings showed that ionizing radiation caused apoptosis in germinal epithelial cells led to the oxidative stress-mediated testicular injury. On the other hand, NAC may be useful in the prevention of testicular injury-suppressed ROS production.

The effects of atorvastatin therapy on rheological characteristics of erythrocyte membrane, serum lipid profile and oxidative status in patients with dyslipidemia.

The statins, most commonly used in the treatment of hyperlipidemia, have certain beneficial effects including improved endothelial function, plaque stability and decreased oxidative stress and inflammation, beyond their lipid-lowering effect in plasma. We evaluated the pleiotropic impact of atorvastatin on erythrocyte structural/mechanical properties and lipid peroxidation in dyslipidemics. The study group included 44 patients with dyslipidemia and was divided into subgroups according to triglyceride and cholesterol levels as hypercholesterolemic (n = 29) and mixed-type hyperlipidemic (n = 15). Subjects were given 10 mg atorvastatin per day for 12 weeks. Changes in serum lipid composition, lipid contents, Na(+)/K(+)-ATPase activity and osmotic fragility in erythrocytes and oxidative stress parameters of erythrocytes and plasma were studied. Atorvastatin therapy improved the serum lipid profile of both subgroups. This alteration was accompanied by a decreased level of cholesterol in erythrocyte membranes. Moreover, enhanced activity of Na(+)/K(+)-ATPase in erythrocytes reflected the improvements in membrane lipids of both subgroups. However, a significant change was observed in osmotic fragility values of the mixed-typed dyslipidemic group. This treatment lowered the lipid peroxidation in plasma and erythrocytes and increased plasma total antioxidant capacity in all groups. The present study shows that the use of atorvastatin reversed the structural and functional features of erythrocyte membranes in dyslipidemic subjects. Also, hypolipidemic therapy had a beneficial impact on a balance between oxidant and antioxidant systems.

Association between plasma monocyte chemoattractant protein-1 levels and the extent of atherosclerotic peripheral artery disease.

Peripheral artery disease occurs at advanced ages and accounts for substantial cardiovascular morbidity and mortality. Monocyte chemoattractant protein-1 (MCP-1), a member of the cysteine-cysteine family of chemokines, is one of the cytokines involved in the pathogenesis of atherosclerosis and is also known as cysteine-cysteine chemokine ligand 2 (CCL2). The aim of the current study was to investigate the association between the extent of atherosclerotic peripheral artery disease (PAD) and the increase in MCP-1 level. Eighty consecutive patients who had undergone peripheral angiography for suspected PAD were included. Of these patients, 48 (60%) had hypertension, 23 (28.8%) had type 2 diabetes mellitus, 39 (48.8%) had a family history of coronary artery disease, 23 (28.8%) were cigarette smokers, and 42 (52.5%) had hypercholesterolemia. Angiography revealed that the peripheral arteries of the lower extremity were normal in 41 (51.3%) patients, whereas 39 (48.7%) patients had varying degrees of PAD. The patients were queried regarding age, gender, and atherosclerotic risk factors. The plasma MCP-1 levels were significantly lower in the patients without PAD than those in the patients with PAD (172.27 ± 38.05 pg/mL vs. 200.87 ± 39.31 pg/mL, p = 0.001). Moreover, as the severity of PAD increases, MCP-1 levels also increase. Thus, the plasma MCP-1 level can be used in the diagnosis of PAD and in determining the extent of atherosclerotic PAD of the lower extremities, as in determining the extent of coronary artery disease.

The effects of atorvastatin treatment on the fibrinolytic system in dyslipidemic patients.

Statins have pleiotrophic effects related to the pathogenesis of atherosclerosis and thrombogenicity of the vessel wall beyond lipid lowering. The aim of the present study was to examine the effect of atorvastatin treatment on the fibrinolytic system in patients with dyslipidemia. The investigation was carried out on 41 dyslipidemic patients (21 males and 20 females) with a mean age of 53.8 years (range, 30-76). The patients were divided into subgroups according to their cholesterol and triglyceride levels as hypercholesterolemic (n = 26) and mixed-type hyperlipidemic (n = 15) and their risk factors for coronary heart disease including age, sex, hypertension, obesity, smoking, and family history. The patients were started on atorvastatin 10 mg/day, and evaluated within 6-12 weeks to assess the changes in fibrinolytic parameters including global fibrinolytic capacity, plasminogen activator inhibitor type-1 and tissue plasminogen activator, and lipids. After successful lipid-lowering therapy, global fibrinolytic capacity (P = 0.003) and tissue plasminogen activator levels (P = 0.04) were found to be increased and plasminogen activator inhibitor type-1 levels (P = 0.02) decreased in dyslipidemic patients. Global fibrinolytic capacity levels increased (P < 0.001) and plasminogen activator inhibitor type-1 levels decreased (P = 0.01) in patients with hypercholesterolemia (n = 26). However, no significant changes were observed in fibrinolytic parameters in patients with mixed-type hyperlipidemia (n = 15). When the patients were separately evaluated according to risk factors, significant beneficial effects on the fibrinolytic system were observed, especially in patients without obesity and hypertension as well as in older patients and males. These findings suggest that atorvastatin treatment has a beneficial effect on the fibrinolytic system in patients with hypercholesterolemia, but not in patients with mixed-type hyperlipidemia. Further studies are needed to show whether higher doses and longer periods of lipid lowering treatment have beneficial effects in patients with mixed type hyperlipidemia and some risk factors.