Pretreatment Of Animals Research Articles

The impact of PPAR-γ/Nrf-2/HO-1, NF-κB/IL-6/ Keap-1, and Bcl-2/caspase-3/ATG-5 pathways in mitigation of DOX-induced cardiotoxicity in an animal model: The potential cardioprotective role of oxyresveratrol and/or dapagliflozin

Antioxidants given concurrently with chemotherapy offer an effective strategy for reducing the negative effects of the drug. One remaining obstacle to the use of doxorubicin (DOX) in chemotherapy is cardiotoxicity. Using vitamin E (Vit. E) as a reference standard, our study focuses on the potential preventive benefits of oxyresveratrol (ORES) and/or dapagliflozin (DAPA) against DOX-induced cardiac injury. Acute cardiotoxicity was noticed after a single intravenous injection of a male rat's tail vein with 10 mg/kg of DOX. Oral doses of ORES (80 mg/kg), DAPA (10 mg/kg), and Vit. E (1 g/kg) were given, respectively. Pretreatment of animals with Vit. E, ORES and/or DAPA revealed a considerable alleviation of heart damage, as evidenced by histopathological change mitigation and a notable drop in serum AST, LDH, CK, CK-MB, and cardiac contents of MDA and NO2−. Also, serum TAC, tissue GSH, and SOD showed substantial increases. Additionally, tissue caspase-3, serum IL-6, and TNF-α were considerably reduced. Moreover, a downregulation in cardiac gene expression of ATG-5, Keap-1, and NF-κB in addition to an upregulation of Bcl-2 gene expression and HO-1, Nrf-2, and PPAR-γ protein expression clearly appeared. Ultimately, ORES and/or DAPA have an optimistic preventive action against severe heart deterioration caused by DOX.

Evaluation of the cardioprotective activity of summer savory (Satureja hortensis L.) extract in experimental rats with Isoproterenol-induced myocardial infarction

BackgroundMyocardial infarction (MI) is a serious heart ailment that requires cutting-edge remedies for effective treatment. This study examines the possible cardioprotective effects of a hydroalcoholic extract from Satureja hortensis L. (HASH) in rats with isoproterenol (ISO) induced myocardial infarction. MethodsThe rats were pretreated orally with hydroalcoholic extract of Satureja hortensis low (200 mg/kg), high dose (400 mg/kg), and metoprolol (10 mg/kg), in their respective groups for 30 days, followed by two subcutaneous doses of isoproterenol (ISO). Blood was obtained to measure biochemicals such as creatine kinase-MB (CK-MB), Troponin I, Alanine transaminase (ALT), Aspartate transaminase (AST), and lactate dehydrogenase (LDH), and an electrocardiogram (ECG) of a rat was recorded after the experiment. Myocardial integrity was examined histopathologically, and malondialdehyde (MDA) levels and antioxidant enzyme concentrations were assessed using heart tissue homogenate. ResultsRats with myocardial infarction caused by ISO displayed significantly (P < 0.001) augmented CK-MB, Troponin I, LDH, AST, and ALT levels with aberrant ECG patterns, and alteration in cardiac mass as well as enhaced oxidative stress marker levels. Besides, biochemical results were validated by myocardium histology. Pre-treatment of animals with a high dose (400 mg/kg) of HASH or standard cardioprotective agent (metoprolol) prevented the ISO-induced alterations in the above parameters to a significant (P < 0.01) level as well as metabolic derangements and functional alterations. ConclusionsOur research suggests that HASH pre-treatment has cardioprotective action and can prevent myocardial toxicity caused by ISO. Therefore, Satureja hortensis L. extract might be a promising therapeutic plant that can be further investigated for potential cardioprotective properties.

Prophylactic effects of Combretum molle boughs on changes in the hematological, biochemical, and histological parameters in dexamethasone-induced insulin-resistant rats

BackgroundCombretum molle (Combretaceae) is a plant used in Cameroon traditional medicine to treat diabetes mellitus. To our knowledge, no studies have been performed on the preventive effects of C. molle on change in hematological, biochemical, and histological parameters of insulin-resistant rats. The aim of the study was to evaluate the preventive effect of C. molle on changes in the hematological biochemical, and histological parameters of insulin-resistant rats. MethodsInsulin resistance was induced for 10 days by subcutaneous injection of dexamethasone (1 mg/kg), one hour after oral pretreatment of animals with distilled water, metformin (40 mg/kg), and C. molle extract (250 and 500 mg/kg). Hematological profile (red blood cells, white blood cells, platelets and their indices), biomarkers of renal and hepatic function, hepatic glycogen level, activity of hepatic enzymes of carbohydrate metabolism, and histological sections of kidney, liver and pancreas were assessed. ResultsC. molle extract (250 and 500 mg/kg) caused a significant decrease (p < 0.05 to p < 0.001) in white blood cells, platelets count, and the activities of fructose 6-diphosphatase, glucose-6-phosphate dehydrogenase, and transaminases. It also caused significant increase (p < 0.05 to p < 0.001) in red blood cells, hemoglobin, albumin, glycogen, urea, uric acid, and creatinine values, and fructose-1,6-diphospatase and glucokinase activity. Histological examination revealed regeneration of beta-cells of the pancreatic islets and preventive renal and hepatic tissues against damages caused by impact of dexamethasone. ConclusionC. molle extract protected insulin-resistant patients from hematological, biochemical, and histopathological changes, there by validating the merits of the use of this plant in traditional medicine to treat diabetes mellitus and its complications.

Animal-assisted psychotherapy in treatment of adults with depressive symptoms: A retrospective quasi-experimental study

Abstract Animal-assisted psychotherapy (AAP), a subspeciality of animal-assisted therapy (AAT), is a relatively new and innovative treatment modality currently provided to all age groups with various mental and behavioral health issues in different clinical settings. As AAP has become more popular, there is a need to evaluate the use of this approach in therapeutic settings. This study assessed AAP in treating adults with depressive symptoms using a modified version of the Patient Questionnaire Depression Module (mPHQ-9). Secondary data were obtained from a therapy site specializing in AAP in the Denver Metro region of the United States from January 2015 to February 2021. Adult participants 18 years and older were assessed at intake and the approximately 6-month treatment mark. A paired-sample t-test found that AAP resulted in a statistically significant decrease in depressive symptomology, with modified PHQ-9 (mPHQ-9) scores from Intake to Time 2 (t (50) = 6.56, p &lt; 0.001). The importance of animals in the participants’ decision to seek therapy also significantly influenced the change in depressive symptoms. The total variance explained by the importance of animals pre-treatment on depressive symptoms for adults with AAP was 8.1%, F (168.69, 1926.14) = 4.29, p = 0.044; moderate effect size (η2 = 0.46) was found. Clinical implications include the function of AAP, which requires a more accurate operational definition and a manualized AAP treatment protocol. AAP is a progressively growing intervention and a promising complementary modality to traditional therapeutic methods for adults with depressive symptoms.

Involvement of the Dopaminergic and Serotonergic Systems in the Antidepressant-like Effect Caused by Ethanolic Extract of Pistacia lentiscus in Tail Suspension Test

Background: Depression is one of the most common psychiatric disorders worldwide and causes disability. There is a need to produce new agents for the treatment of depression with the maximum efficiency and the lowest side effects. The positive effects of Pistacia lentiscus have been reported in the central nervous system and different disorders. Objectives: This study evaluated the antidepressant-like effect of the ethanolic extract of P. lentiscus (EEPL) in a mouse model and its possible mechanisms. Methods: The male NMRI mice (20 - 25 g) intraperitoneally (i.p.) received vehicle (10 mL/kg), imipramine (30 mg/kg), fluoxetine (20 mg/kg, i.p.), and EEPL (50 - 400 mg/kg). After 45 minutes, the animals were subjected to a tail suspension test (TST). The open-filed test (OFT) was used to assess the animal’s locomotion. To elucidate possible monoaminergic mechanisms, the mice were pre-treated with various receptor antagonists 1 hour before the most effective dose of EEPL. Results: The administration of EEPL (100 - 400 mg/kg) induced an antidepressant-like effect (37.5%, 49.3%, and 63.9% reduction, respectively) in the TST (P &lt; 0.001) without considerable effects on animal locomotion in OFT (P &gt; 0.05). The antidepressant-like effect of EEPL (200 mg/kg) was blocked by the pre-treatment of animals with SCH23390, sulpiride, haloperidol, ketanserin, WAY100135, and p-chlorophenylalanine (pCPA) (P &lt; 0.001), but not with prazosin, yohimbine, or propranolol (P &gt; 0.05). Conclusions: The results show that the antidepressant-like effect of EEPL is mediated by the modulation of dopaminergic and serotonergic systems. Overall, the results suggested that EEPL exerted an antidepressant-like activity in the mouse model of depression, which might be considered a useful drug in the management of depression.

Repeated pre-exposure to morphine inhibited the amnesic effect of ethanol on spatial memory: Involvement of CaMKII and BDNF

Evidence has suggested that addiction and memory systems are related, but the signaling cascades underlying this interaction have not been completelyealed yet. The importance of calcium-calmodulin-dependent protein kinase II (CaMKII) and brain-derived neurotrophic factor (BDNF) in the memory processes and also in drug addiction has been previously established. In this present investigation, we examined the effects of repeated morphine pretreatment on impairment of spatial learning and memory acquisition induced by systemic ethanol administration in adult male rats. Also, we assessed how these drug exposures influence the expression level of CaMKII and BDNF in the hippocampus and amygdala. Animals were trained by a single training session of 8 trials, and a probe test containing a 60-s free-swim without a platform was administered 24 h later. Before training trials, rats were treated with a once-daily subcutaneous morphine injection for 3 days followed by a 5-day washout period. The results showed that pre-training ethanol (1 g/kg) impaired spatial learning and memory acquisition and down-regulated the mRNA expression of CaMKII and BDNF. The amnesic effect of ethanol was suppressed in morphine- (15 mg/kg/day) pretreated animals. Furthermore, the mRNA expression level of CaMKII and BDNF increased significantly following ethanol administration in morphine-pretreated rats. Conversely, this improvement in spatial memory acquisition was prevented by daily subcutaneous administration of naloxone (2 mg/kg) 15 min prior to morphine administration. Our findings suggest that sub-chronic morphine treatment reverses ethanol-induced spatial memory impairment, which could be explained by modulating CaMKII and BDNF mRNA expressions in the hippocampus and amygdala.

An Observationa Study on the Role of Zinc Sulphate in Paracetamol Toxicity

Aim: The aim of this study was to determine the role of Zinc Sulphate as an agent of hepatoprotective in the acetaminophen-induced changes of histopathological nature in the model of animals. Methodology: The design of this study was observational study design. This study was conducted at Allied Hospital Faisalabad and the duration of this study was from April 2022 to July 2022. Our research sample was 90 albino rats with the range of weight from 18 – 32 grams and we made three groups each group consisting of thirty albino rats. Control group was A group and normal saline level was maintained in this group as 0.9%; acetaminophen was given (250 mg / kg) in B group through a single dose; Zinc Sulphate (1 – 5 mg / kg) was given to C group for a duration of 1 – 7 days before the acetaminophen (250 mg / kg) Sigle dose. After the six hours’ duration was conducted biochemical studies after giving acetaminophen to albino rats. At last step of the treatment weight of all animals was checked at than sacrificed. Histopathological and gross examination was carried out for liver and statistical evaluation of the data was carried out through Chi-Square test. Results: Demonstration of the zinc’s protective effect was made through serum concentration reduction level of the enzymes of liver such as aspartate aminotransferase, lactate dehydrogenase, alanine aminotransferase and serum sorbitol dehydrogenase, including the histopathological centrilobular congestion changes, necrosis and hepatocellular degeneration. We observed through the histopathological evaluation that typical changes in pathological environment of centri-zonal necrosis, leukocyte infiltration, steatosis, edema in animals and portal tiraditos those were treated only with acetaminophen. Animal pretreatment through zinc sulphate lead the whole procedure to dependent on the dose for the avoidance of various changes. Practical Implication: In the practical implication of this study the determination of the Zinc Sulphate role as an agent of hepatoprotective in the acetaminophen-induced changes of histopathological nature in the model of animals. Conclusion: It is concluded that Zinc is responsible for the production of hepato-protective effect with the prevention of ultrastructural hepatic tissue injuries and also causes free amino acid metabolism disturbance which is a result of the acetaminophen toxic dose. Keywords: Acetaminophen, Zinc, Liver Toxicity And Hepato-Protective Effect.

Serum amyloid A, haptoglobin and ceruloplasmin levels before and after treatment in cattle with dermatophytosis

The aim of this study is to determine the changes in serum amyloid A (SAA), haptoglobin (Hp) and ceruloplasmin (Cp) levels before and after treatment in cattle with dermatophytosis. The animal material of the study consisted of a total of 30 cattle, 20 with dermatophytosis and 10 healthy, of different ages and genders. Blood was taken from the sick animals twice, before and after the treatment, and once from the healthy animals, and their serum was separated. The obtained sera were stored at -20 ºC until the Hp, SAA and Cp levels were measured. Trichoben® (Interhas, TR) vaccine was administered to the sick animals twice, 14 days apart. When the pre-treatment and post-treatment serum Hp, SAA and Cp values of the sick animals were statistically compared, it was determined that the pre-treatment values were significantly higher (P&amp;lt;0.001) than the post-treatment values. Similarly, when the values of pre-treatment and control animals were compared, it was seen that the difference was significant (P&amp;lt;0.001). When the serum SAA, Hp and Cp values of the animals in the post-treatment and control groups were compared, it was determined that the difference was statistically insignificant (P&amp;gt;0.05). As a result, it was determined that SAA, Hp and Cp values, which are positive acute phase proteins, increased significantly in cattle with dermatophytosis and these values decreased with treatment. According to this result, it was concluded that serum SAA, Hp and Cp values are important biomarkers in the evaluation of the prognosis of the disease in cattle with dermatophytosis.

Antidepressant-like Properties of Melatonin and Atorvastatin Combination following the Restraint Stress in Mice: A Study of Oxidative Stress Factors.

Antidepressant properties of melatonin and atorvastatin have been reported by clinical and experimental studies. Since both melatonin and atorvastatin possess antioxidant properties and considering the involvement of oxidative stress factors in depression, the aim of the present investigation was to study the possible role of oxidative stress factors in the antidepressant- like effect of melatonin and atorvastatin combination in mice forced swimming test. Following the induction of restraint stress, mice were randomly divided into eight groups including the non-stressed and stressed vehicle-treated groups, melatonin- and atorvastatintreated groups, a combination of melatonin and atorvastatin-treated group, and fluoxetineadministrated group. The open field test (OFT) and forced swimming test (FST) were carried out, and the hippocampus and prefrontal cortex were removed for the measurement of oxidative stress factors. Induction of restraint stress increased the immobility time in FST, and melatonin (10 mg/kg) significantly reduced it. Atorvastatin at both doses of 1 and 10 mg/kg could not alter the immobility time, significantly. Co-administration of melatonin and atorvastatin (10 mg/kg) exerted a significant antidepressant-like response and decreased the immobility time compared with melatonin or atorvastatin (10 mg/kg), alone. Induction of restraint stress elevated the malondialdehyde (MDA) levels in mice's hippocampus, while pretreatment of animals with atorvastatin (10 mg/kg) could reverse it. The co-administration of melatonin and atorvastatin (10 mg/kg) increased the cortical superoxide dismutase (SOD) activity compared with atorvastatin alone, but could not alter the catalase (CAT) activity. It is concluded that atorvastatin might augment the antidepressant-like properties of melatonin in FST.

Natural Antibodies Mediate Protection Against Acinetobacter baumannii Respiratory Infections.

Acinetobacter baumannii causes a wide range of dangerous infections due to the emergence of pandrug-resistant strains. Therefore, there is a need for alternative therapeutics to treat these infections, including those targeting the host immune responses. However, immune responses, especially the humoral response against this pathogen, are poorly understood. This study investigated the lymphocyte-mediated innate immune resistance to A. baumannii AB5075 pulmonary infection using B- and T-cell-deficient (Rag2-/-) mice, the protective effect of natural antibodies (NAbs), and the expression of complement-mediated responses using a mouse pneumonia model. Our results showed that intranasally infected Rag2-/- mice are impaired in clearing bacteria from lung, liver, and spleen at 24 hours postinfection compared to wildtype mice. Animal pretreatment with normal mouse serum or purified antibodies from naive mice rescued Rag2-/- mice from infection. Analysis of C3 complement protein binding demonstrated that NAbs increased C3 protein deposition on A. baumannii cells, indicating the activation of the classical complement pathway by NAbs. Overall, our study shows that NAbs mediate innate immune resistance against A. baumannii, a finding that may lead to the development of effective therapies against human infections caused by this antibiotic-resistant A. baumannii.

Morus alba fruit diet ameliorates cognitive deficit in mouse model of streptozotocin-induced memory impairment.

Mounting evidence shows that dietary intake of fruits with polyphenols is beneficial to improve impaired memory functions. This study explored the preventive as well as therapeutic effects of diet enriched with Morus alba fruits extract (DEMA) in streptozotocin (STZ) induced mouse model of memory impairment. The study consisted of two facets: one aspect consisted of pretreatment of animals with DEMA for two weeks followed by STZ (i.c.v) intervention and the second phase involved induction of dementia with STZ (i.c.v) followed by treatment with DEMA for 14days. Cognitive functions of animals were measured by Morris Water Maze test and to delineate the associated mechanism of action, brain biochemical estimations (acetyl-cholinesterase activity, myeloperoxidase activity, thiobarbituric acid reactive species, superoxide dismutase activity, reduced glutathione and nitrite/nitrate) and histopathological studies (haematoxylin and eosin staining) were performed. Pre- and post- treatment with DEMA significantly prevented and attenuated, respectively, the detrimental effects of STZ on mice brain. The results demonstrated that dietary modification, by incorporation of M. alba fruits, reduces the incidence and aids in treatment of memory disorder in mice by reducing central cholinergic activity, decreasing oxidative stress and preventing neurodegeneration.

Naringin promotes positive inotropism in atrial tissue through β-AR/PKA-dependent pathway

Naringin is a flavonoid glycoside found in citrus fruits and grapes with a wide range of therapeutic actions. We aimed to study the inotropic effect of naringin on rat-isolated atria, dissecting intracellular mechanisms involved in this response. Concentration-response curves of naringin (0.003-6 mM) were obtained before and after pre-incubation with selective antagonists. Our results showed that naringin presented a biphasic inotropic response, with a positive inotropic effect at low and middle concentrations (0.003-2.0 mM), and a negative inotropic effect at high concentrations (above 3 mM). Pre-incubation with propranolol or atenolol (β-adrenergic receptors antagonists, β-AR), H89 (protein kinase-A inhibitor, PKA), nifedipine (L-type Ca2+ channel blocker), or ryanodine (ryanodine receptor inhibitor) fully abolished the positive inotropic effect induced by naringin. Pre-treatment of animals with reserpine, catecholamine-depleting drug, also prevented the increase of atrial contractility evoked by naringin. Altogether, we show that naringin causes a positive inotropic effect in isolated atria through β-AR/PKA-dependent pathway.

Origanum majorana L. extract alleviates dexamethasone-induced hepatotoxicity, oxidative stress and pathological alterations in vivo

BackgroundOriganum majorana (O. majorana) is one of the most widely used herbs in Egypt due to its antioxidant, anti-inflammatory, anti-genotoxic, antimutagenic, anticoagulant and beneficial properties. Our study's main goal is to determine how well O. majorana leaf extract can reduce hepatotoxicity and oxidative stress produced by dexamethasone (DXM). Thirty female rats were divided into three groups of ten. Animals in group1 received distilled water daily for eight weeks and served as control. Those in group 2 exposed subcutaneously to 0.1 mg/kg body weight of DXM three times per week for eight weeks and served as the toxic group, while those in group 3 were treated daily and orally with 100 mg/kg of O. majorana aqueous extract + 0.1 mg/kg of DXM three times per week for eight weeks and served as treated group.ResultsDue to DXM treatment, the activities of liver function markers were significantly elevated (P < 0.0001), whereas O. majorana pretreated animals improved or reduced the elevated liver function enzyme activities. Dexamethasone administration considerably enhancing oxidative stress which rose (P < 0.0001) MDA concentration and attenuated the antioxidant defense system by decreasing the activities of GST, GSP, GSR, and CAT significantly in liver homogenate when compared to control animals. The results further demonstrated that pretreatment with O. majorana boosted the antioxidant defenses against the damaging effects of DXM.ConclusionIt can be said that dexamethasone exposure induced- hepatotoxicity and oxidative stress in rats that repaired by O. majorana aqueous extract which had the ability to reduce the impact of hepatic damage. To evaluate the health benefits and safety of O. majorana in individuals, more clinical research is needed.Graphical abstract

Sumc (Rhus coriaria L.) fruit ameliorates paracetamol-induced hepatotoxicity

Sumac [Rhus coriaria L. (Anacardiaceae)] is a widely used spice in the Middle East. In this study, the hepatoprotective effects of sumac fruit were evaluated using a rat model of paracetamol-induced liver injury. The experimental design relies on the pretreatment of rats with intraperitoneal sumac extract followed by a toxic dose of paracetamol. Tissue alterations, serum levels of oxidative stress markers, as well as gene expression of immunomarkers were evaluated. Rats pre-treated with sumac displayed attenuated signs of toxicity. Upon paracetamol intoxication, sumac-pretreated animals showed a minimal increase in liver enzyme levels. In parallel, serum albumin and total protein levels were close to normal. Moreover, pretreated sumac animals had preserved hepatocyte morphology, whereas unprotected animals had necrotic deformations. Importantly, these effects were dose-dependent and comparable to the silymarin-treated positive control group. In conclusion, sumac extract offers a potential hepatoprotective regimen against xenobiotic-induced hepatotoxicity and for oxidative stress management.

The neurotoxic mechanism of Jack Bean Urease in insects involves the interplay between octopaminergic and dopaminergic pathways

In the last decades, the entomotoxicity of JBU and its derived peptides became an object of study, due mainly to the ubiquitous interaction of these compounds with different species of insects and their potential as natural insecticides. In this work, we investigated the neurotoxic effects of JBU in Nauphoeta cinerea cockroaches by dissecting pharmacologically the monoaminergic pathways involved. Selective pharmacological modulators for monoaminergic pathways in in vivo and ex vivo experimental models were employed. Thus, the analysis of N. cinerea neurolocomotory behavior demonstrated that JBU (1.5 and 3 μg/g) induces a significant decrease in the exploratory activity. In these assays, pretreatment of animals with phentolamine, SCH23390 or reserpine, interfered significantly with the response of JBU. Using in vivo abductor metathoracic preparations JBU (1.5 μg/g) induced progressive neuromuscular blockade, in 120 min recordings. In this set of experiments, the previous treatment of the animals with phentolamine, SCH23390 or reserpine, completely inhibited JBU-induced neuromuscular blockade. The recordings of spontaneous compound neural action potentials in N. cinerea legs showed that JBU, only in the smallest dose, significantly decreased the number of potentials in 60 min recordings. When the animals were pretreated with phentolamine, SCH23390, or reserpine, but not with mianserin, there was a significant prevention of the JBU-inhibitory responses on the action potentials firing. Meanwhile, the treatment of the animals with mianserin did not affect JBU's inhibitory activity. The data presented in this work strongly suggest that the neurotoxic response of JBU in N. cinerea involves a cross talking between OCTOPAMIN-ergic and DOPAMIN-ergic nerve systems, but not the SEROTONIN-ergic neurotransmission. Further molecular biology studies with expression of insect receptors associated with voltage clamp techniques will help to discriminate the selectivity of JBU over the monoaminergic transmission.

Dimethyl Sulfoxide Induces Hemolysis and Pulmonary Hypertension.

Vascular and lung injury are well established complications associated with hemolytic disorders, and hemolysis associated pulmonary hypertension (PH) has emerged as the most serious complication of sickle cell disease. The causal relationship between intravascular hemolysis and the development of PH is still under investigation. Previously we have shown that repetitive administration of hemolyzed autologous blood causes PH in rats. Dimethyl sulfoxide (DMSO), a widely used solvent and anti-inflammatory agent, induces hemolysis in vivo. We hypothesized that repetitive administration of DMSO would induce PH in rats. We also examined hemolysis-induced release of adenosine deaminase (ADA) and arginase from red blood cells, which may amplify hemolysis-mediated vascular injury. Acute administration of DMSO (1.5ml/30 min into the right atrium) induced intravascular hemolysis and pulmonary vasoconstriction. DMSO-induced increase in right ventricular peak systolic pressure (RVPSP) was associated with increased release of ADA. Notably, the acute increase in RVPSP was attenuated by administration of an adenosine A2A receptor agonist or by pretreatment of animals with ADA inhibitor erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA). Repetitive administration of DMSO for 10 days produced anemia, hemoglobinuria, hemoglobinemia, splenomegaly, and development of PH. Histopathological analysis revealed pulmonary vascular remodeling. The presented data describe a new model of hemolysis induced PH, suggesting that hemolysis is mechanistically related to pulmonary hypertension, and pointing to a potential pathogenic role that adenosine deaminase and accelerated adenosine metabolism may play in hemolysis associated pulmonary hypertension.

In Vivo Assessments of Mesoblastic Nephroma (Ne/De) and Myelomonoblastic Leukaemia (My1/De) Tumour Development in Hypercholesterolemia Rat Models.

Given the rising prevalence of lipid metabolic disorders and malignant diseases, we aimed to establish an in vivo hypercholesterinaemic tumour-bearing rat model for the induction and assessment of these conditions. A normal standard CRLT/N, 2 (baseline),- or 4 (2 + 2, pretreated)-week-long butter and cholesterol rich (BCR) diet was applied to mesoblastic nephroma (Ne/De) and myelomonoblastic leukaemia (My1/De) tumour-bearing and healthy control Long-Evans and Fischer 344 rats. The beginning of chow administration started in parallel with tumour induction and the 2 weeks of pre-transplantation in the baseline and pretreated groups, respectively. Fourteen days post-inoculation, the measurement of lipid parameters and [18F]F-FDG PET/MRI examinations was executed. The comparable lipid status of baseline healthy and tumorous rats proves that regardless of tumour presence, BCR-based hypercholesterolemia was achieved. A higher tumour mass among pretreated tumorous animals was found when compared to the control groups (p &lt; 0.05, p &lt; 0.01). Further, a visually greater [18F]F-FDG accumulation was observed in pretreated BCR tumorous animals; however, the quantitative data (SUVmean: 9.86 ± 0.98, 9.68 ± 1.24; SUVmax: 19.63 ± 1.20; 17.56 ± 3.21 for Ne/De and My1/De, respectively) were not statistically significantly different from those of the CRLT/N tumorous rats (SUVmean: 8.40 ± 1.42, 7.22 ± 1.06 and SUVmax: 15.99 ± 2.22, 12.46 ± 1.96 for control Ne/De and My1/De, respectively). Our model seems to be appropriate for simultaneously investigating hypercholesterolemia and cancer in the same rat.

Conjugated linoleic acid downregulates Alzheimer's hallmarks in aluminum mouse model through an Nrf2-mediated adaptive response and increases brain glucose transporter levels.

Mitochondrial dysfunction, oxidative stress, inflammation and glucose dysmetabolism are pathological signs of Alzheimer's disease (AD). Dietary aluminum (Al) overload is often used to induce AD in rodents and trigger the onset of oxidative-stress hallmarks resembling those of the human disease. The Nuclear factor erythroid 2-related factor 2 (Nrf2), owing to its key role in redox homeostasis, mitochondrial function and inflammation, is a promising drug target for neurological disorders, but only a few data are available on its modulatory effects on glucose transporter expression levels. While it has been found that the protective effect of Conjugated linoleic acid (CLA) occurs through the activation of an Nrf2-mediated adaptive response, its beneficial effect on the considered pathological signs in the Al-induced model has not been established yet. Thirty-five male BalbC mice were divided into 5 groups: two Al-intoxicated groups were treated for 5 weeks with low or high Al doses (8 or 100mg/kg/day in drinking water, respectively; L or H). Two groups of animals, orally supplemented with CLA (600mg/kgbw/day) for 7 weeks (2 preliminary weeks plus the 5-week treatment with Al; CLA+L, CLA+H) were used to investigate its protective effect, while untreated mice were used as control (Cntr). We provide evidence that mitochondrial dysfunction, Nrf2 alteration, inflammation and Acetylcholinesterase (AChE) hyperactivation can occur even from L exposure. Interestingly, animal pre-treatment with an allometric CLA dose led to significant downregulation of the toxic effects elicited by L or H, likely through the activation of an adaptive response. In conclusion, CLA ability to increase the level of glucose transporters - along with its antioxidant and anti-inflammatory effect - expands the therapeutic targets of these molecules and comes out as an intriguing suitable candidate for the treatment of multifactorial disease.

A magnetic pulse does not affect free-flight navigation behaviour of a medium-distance songbird migrant in spring.

Current evidence suggests that migratory animals extract map information from the geomagnetic field for true navigation. The sensory basis underlying this feat is elusive, but presumably involves magnetic particles. A common experimental manipulation procedure consists of pre-treating animals with a magnetic pulse, with the aim of re-magnetising particles to alter the internal representation of the external field prior to a navigation task. Although pulsing provoked deflected bearings in caged songbirds, analogous studies with free-flying songbirds yielded inconsistent results. Here, we pulsed European robins (Erithacus rubecula) at an offshore stopover site during spring migration and monitored their free-flight behaviour with a regional-scale network of radio-receiving stations. We found no pulse effect on departure probability, nocturnal departure timing departure direction or consistency of flight direction. This suggests either no use of the geomagnetic map by our birds, or that magnetic pulses do not affect the sensory system underlying geomagnetic map detection.

Pharmacological evaluation of newly synthesized organotin IV complex for antiulcer potential

The present study aims to investigate the newly synthesized organotin (IV) complex (2E, 2′E) dibutylstannanediyl bis (4-(4-nitrophenyl) amino)-4-oxobut-2-enoate (DTN) for its anti-ulcer potential. Characterization performed by carbon nuclear magnetic resonance spectroscopy proved that all values are in the expected ranges of the new compound. Gastroprotective activity of DTN was evaluated through in-silico, anti-H. pylori, in-vitro, in-vivo, and ex-vivo proteomic analysis. In-silico analysis shows that DTN possess stable binding with protein targets involved in gastric ulcer pathophysiology. DTN exhibited an inhibitory effect against 2,2-diphenyl-1-picrylhydrazyl, H. pylori and hydrogen potassium ATPase (H+/K+-ATPase). The antiulcer activity was performed using an ethanol-induced gastric ulcer model in rats. Anti-oxidant profile of DTN showed a significant increase in glutathione-S-transferase, glutathione and catalase levels whereas lipid peroxidation levels were reduced. Histopathological findings confirmed that DTN protected the gastric mucosa of rats. Inflammatory markers tumor necrosis factor-alpha, nuclear factor kappa B, cyclooxygenase-2, interleukin 6 and interleukin-1β were reduced and prostaglandin-E2 restored expression of these cytokines in DTN pretreated animals when analyzed by using immunohistochemistry, enzyme-linked immunosorbent assay and western blot techniques. In real-time polymerase chain reaction technique, the expression of H+/K+-ATPase was downregulated in DTN pretreated group. DTN did not cause any mortality up to 400 mg/Kg. This study indicates that the newly synthesized compound DTN, possess stable binding against selected targets. DTN exhibits a gastro-protective effect, mediated via anti-H. pylori, H+/K+-ATPase inhibition, anti-oxidant and anti-inflammatory pathways, exploring its therapeutic potential in gastric ulcer management.