Effect of sildenafil on neuroinflammation and synaptic plasticity pathways in experimental autoimmune encephalomyelitis.

Multiple sclerosis (MS) is a chronic immuno-inflammatory disease of the central nervous system characterized by demyelination and axonal damage. Cognitive changes are common in individuals with MS since inflammatory molecules secreted by microglia interfere with the physiological mechanisms of synaptic plasticity. According to previous data, inhibition of PDE5 promotes the accumulation of cGMP, which inhibits neuroinflammation and seems to improve synaptic plasticity and memory.

cGMP signaling pathway in hepatic encephalopathy neuroinflammation and cognition.

Hepatic encephalopathy (HE) is a complex neuropsychiatric syndrome that results from liver failure and is characterized by a wide range of symptoms such as alteration in the sleep-waking cycle, neuromuscular coordination, mood, and cognition. The deregulation of nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) signaling pathway is thought to play an important role in the etiology and progression of neurodegenerative diseases, and several studies pointed that the cGMP signaling is impaired in patients with HE and experimental models of chronic hyperammonemia. This review aimed to briefly present the current knowledge of the cGMP signaling pathways in neuroinflammation, neurogenesis, and memory in hepatic encephalopathy and its potential therapeutic role.

Tadalafil restores long-term memory and synaptic plasticity in mice with hepatic encephalopathy.

Background And Aim: Tadalafil displays important neuroprotective effects in experimental models of neurodegenerative diseases, however its mechanisms of action remain poorly understood. The aim of the present study was to investigate the action of Tadalafil on learning and memory, neuroinflammation, glial cell activation and neuroprotection in the experimental model of hepatic encephalopathy (HE) induced by Thioacetamide (TAA) in mice.

Methods: Mice received intraperitoneal injections of TAA, for 3 consecutive days, reaching the final dose of 600 mg/kg.

Preventive role of metformin on peripheral neuropathy induced by diabetes.

Metformin is the first line drug in the treatment of type 2 diabetes, however, little is known about its therapeutic potential to prevent or delay damage to the peripheral nerve. Thus, the aim of this study was to investigate whether metformin is able to attenuate the neuroinflammatory response in sciatic nerve of insulin-dependent diabetic mice. Swiss Webster mice were divided into four groups: Control, Diabetic (STZ), Diabetic +100 mg/kg/day of metformin (STZ + M100) and Diabetic +200 mg/kg/day of metformin.

A new diethylcarbamazine formulation (NANO-DEC) as a therapeutic tool for hepatic fibrosis.

The aim of the present study was to assess if the uninterrupted and prolonged administration of nanoparticles containing diethylcarbamazine (NANO-DEC) would cause liver, kidney and heart toxicity and then analyze for the first time its action in model of liver fibrosis. Thus, NANO-DEC was administered in C57BL/6 mice daily for 48 days, and at the end the blood was collected for biochemical analyzes. In the long-term administration assay, the evaluation of serological parameters (CK-MB, creatinine, ALT, AST and urea) allowed the conclusion that NANO-DEC prolonged administration did not cause hepatic, renal and cardiac damage.

Sildenafil ameliorates EAE by decreasing apoptosis in the spinal cord of C57BL/6 mice.

Apoptosis is one form of cell death that is intimately related to health and pathological conditions. In most neuroinflammatory and/or neurodegenerative diseases, apoptosis is associated with disease development and pathology and inhibition of this process leads to considerable amelioration. It is becoming evident that apoptosis also participates in the pathogenesis of Multiple Sclerosis (MS) and its animal model, Experimental Autoimmune Encephalomyelitis (EAE).

New thiazolidinedione LPSF/GQ-2 inhibits NFκB and MAPK activation in LPS-induced acute lung inflammation.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are responsible for high mortality rates in critical patients. Despite >50 years of intensive research, there is no pharmacologically effective treatment to treat ALI. PPARs agonists, chemically named thiazolidinediones (TZDs) have emerged as potential drugs for the treatment of ALI and ARDS due to their anti-inflammatory efficacy.

Characterization and evaluation of nanoencapsulated diethylcarbamazine in model of acute hepatic inflammation.

Previous studies from our laboratory have demonstrated that Diethylcarbamazine (DEC) is a potent anti-inflammatory drug. The aim of the present study was to characterize the nanoencapsulation of DEC and to evaluate its effectiveness in a model of inflammation for the first time. C57BL/6 mice were divided into six groups: 1) Control; 2) Carbon tetrachloride (CCl4); 3) DEC 25mg/kg+CCl4; 4) DEC 50mg/kg+CCl4; 5) DEC-NANO 05mg/kg+CCl4 and 6) DEC-NANO 12.

Diethylcarbamazine attenuates the expression of pro-fibrogenic markers and hepatic stellate cells activation in carbon tetrachloride-induced liver fibrosis.

Background And Aim: While diethylcarbamazine citrate (DEC) displays important anti-inflammatory effects in experimental models of liver injury, the mechanisms of its action remain poorly understood. The aim of the present study was to investigate the fibrolytic potential of DEC.

Methods: Mice receive two injections of carbon tetrachloride (CCl) per week for 8 weeks.

RNA binding protein, tristetraprolin in a murine model of recurrent pregnancy loss.

Recurrent pregnancy loss is a major reproductive pathology affecting 1-5% of pregnant women worldwide. A distinct feature of this reproductive pathology is involvement of key inflammatory cytokines and transcription factors such as tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6) and nuclear factor kappa beta (NF-κB). Special classes of RNA-binding proteins regulate the transcripts of many of these important cytokines and regulatory factors via binding to the 3' untranslated regions (UTRs) and/or poly(A) tail and destabilizing/stabilizing the transcript.

Effects of metformin on inflammation and short-term memory in streptozotocin-induced diabetic mice.

The aim of the present study was to analyze the action of metformin on short-term memory, glial cell activation and neuroinflammation caused by experimental diabetic encephalopathy in C57BL/6 mice. Diabetes was induced by the intraperitoneal injection of a dose of 90mg/kg of streptozotocin on two successive days. Mice with blood glucose levels ≥200dl/ml were considered diabetic and were given metformin hydrochloride at doses of 100mg/kg and 200mg/kg (by gavage, twice daily) for 21 days.

Diethylcarbamazine reduces chronic inflammation and fibrosis in carbon tetrachloride- (CCl₄-) induced liver injury in mice.

This study investigated the anti-inflammatory effects of DEC on the CCl4-induced hepatotoxicity in C57BL/6 mice. Chronic inflammation was induced by i.p.

Diethylcarbamazine inhibits NF-κB activation in acute lung injury induced by carrageenan in mice.

Diethylcarbamazine citrate (DEC) is widely used to treat lymphatic filariasis and Tropical Pulmonary Eosinophilia. A number of studies have reported a possible role in the host immune system, but exactly how DEC exerts this effect is still unknown. The present study reports the effects of DEC pretreatment on NF-κB regulation using the pleurisy model induced by carrageenan.

Reduction of carrageenan-induced acute pulmonary inflammation in mice by novel thiazolidinedione derivative LPSF/RA-4.

A number of studies have demonstrated the biological activities of peroxisome proliferator-activated receptors. However, few studies have addressed the effects of the agonists of these receptors on lung diseases. The aim of the present study was to evaluate the anti-inflammatory action of a novel synthetic thiazolidine derivative (5Z)-3-benzyl-5-(1H-indol-3-ylmethylene)-thiazolidine-2,4-dione (LPSF/RA-4) on acute lung inflammation (pleurisy) induced by carrageenan.