Effects of Low-Intensity Transcranial Pulsed Ultrasound Treatment in a Model of Alzheimer's Disease.

Alzheimer's disease (AD) is the most common neurodegenerative disease. One of the main pathology markers of AD is the beta-amyloid plaques (ßA1-42) created from residues of the badly processed amyloid precursor protein. The accumulation of these plaques can induce neuroinflammation and oxidative stress and impair antioxidant mechanisms, culminating in cognitive and memory deficits. New therapies are necessary to treat AD as the approved drugs do not treat the progress of the disease. Transcranial low-intensity pulsed ultrasound (LIPUS) affects brain metabolism and could be tested as a treatment for AD. This study was aimed at evaluating the LIPUS treatment in a model of AD induced by ßA1-42 intracerebroventricularly (ICV) and its effects on learning memory, neurotrophins, neuroinflammation and oxidative status. ßA1-42 was administered ICV 24 h before the start of a 5-wk LIPUS treatment. The treatment with LIPUS improved recognition memory, as well as increasing nerve growth factor ß and brain-derived neurotrophic factor levels in the hippocampus and cortex. There was a decrease in protein damage in the hippocampus treated with LIPUS. Neuroinflammation and oxidative stress were not present in the AD model used. The results indicated that LIPUS is a novel and promising adjuvant strategy for treatment of the late stage of AD.

Effects of Zingiber officinale extract supplementation on metabolic and genotoxic parameters in diet-induced obesity in mice.

Obesity is an epidemic associated with many diseases. The nutraceutical Zingiber officinale (ZO) is a potential treatment for obesity; however, the molecular effects are unknown. Swiss male mice were fed a high-fat diet (59 % energy from fat) for 16 weeks to generate a diet-induced obesity (DIO) model and then divided into the following groups: standard diet + vehicle; standard diet + ZO; DIO + vehicle and DIO + ZO. Those in the ZO groups were supplemented with 400 mg/kg per d of ZO extract (oral administration) for 35 d. The animals were euthanised, and blood, quadriceps, epididymal fat pad and hepatic tissue were collected. DIO induced insulin resistance, proinflammatory cytokines, oxidative stress and DNA damage in different tissues. Treatment with ZO improved insulin sensitivity as well as decreased serum TAG, without changes in body weight or adiposity index. TNF-α and IL-1ß levels were lower in the liver and quadriceps in the DIO + ZO group compared with the DIO group. ZO treatment reduced the reactive species and oxidative damage to proteins, lipids and DNA in blood and liver in obese animals. The endogenous antioxidant activity was higher in the quadriceps of DIO + ZO. These results in the rat model of DIO may indicate ZO as an adjuvant on obesity treatment.

Ginger and avocado as nutraceuticals for obesity and its comorbidities.

Obesity is a worldwide epidemic and is one of the factors involved in the etiology of type 2 diabetes mellitus. Obesity induces low-grade inflammation and oxidative stress. The treatment for obesity involves changes in diet, physical activity, and even medication and surgery. Currently, the use of nutraceutical compounds is associated with health benefits. Ginger and avocado are used for many people all around the world; however, its effect as a nutraceutical compound is less known by the general population. For this reason, we searched information of the literature to point its effects on distinct mechanisms of defense against the obesity its comorbidities. The present review aimed showing that these nutraceuticals may be useful in obesity treatment. Reports have shown that ginger and avocado induce antioxidant and anti-inflammatory effects by improving enzymatic activity and modulating obesity-related impairments in the anti-inflammatory system in different tissues, without side effects. Furthermore, ginger and avocado were found to be effective in reversing the harmful effects of obesity on blood lipids. In conclusion, on the basis of the positive effects of ginger and avocado in in vitro, animal, and human studies, these nutraceuticals may be useful in obesity treatment.

Therapeutic effects of iontophoresis with gold nanoparticles in the repair of traumatic muscle injury.

Studies have shown the benefits of gold nanoparticles (GNPs) in muscle and epithelial injury models. In physiotherapy, the use of the microcurrent apparatus is associated with certain drugs (Iontophoresis) to increase the topical penetration and to associate the effects of both therapies. Therefore, the objective of this study was to investigate the effects of iontophoresis along with GNPs in the skeletal muscle of rats exposed to a traumatic muscle injury. We utilised 50 Wistar rats randomly divided in to five experimental groups (n = 10): Control group (CG); Muscle injury group (MI); MI + GNPs (20 nm, 30 mg kg-1); MI + Microcurrent (300 µA); and MI + Microcurrent + GNPs. The treatment was performed daily for 7 days, with the first session starting at 24 h after the muscle injury. The animals were sacrificed and the gastrocnemius muscle was surgically removedand stored for the proper evaluations. The group that received iontophoresis with GNPs showed significant differences in inflammation and oxidative stress parameters and in the histopathological evaluation showed preserved morphology. In addition, we observed an improvement in the locomotor response and pain symptoms of these animals. These results suggest that the association of boththerapies accelerates the inflammatory response of the injured limb.

Intranasal insulin treatment modulates the neurotropic, inflammatory, and oxidant mechanisms in the cortex and hippocampus in a low-grade inflammation model.

The inflammatory process plays a critical role in the development of neurodegenerative diseases. Insulin is used in preclinical and clinical studies of neurological disorders. Its intranasal (IN) administration directly in the brain allows for its peripheral metabolic effects to be avoided. Swiss male mice were injected with lipopolysaccharide (LPS) (0.1 mg/kg) to induce low-grade inflammation. IN insulin treatment was initiated 4 h later at a dose of 1.7 IU once daily for 5 days. LPS induced cognitive deficits, which the IN insulin treatment reversed. LPS significantly decreased, whereas IN insulin significantly increased the levels of brain-derived neurotrophic factor (BDNF) and nerve growth factor-ß in the cortex. In the hippocampus, IN insulin significantly decreased the BDNF level. LPS significantly increased the interleukin (IL)-6 levels in the cortex, while IN Insulin significantly decreased its levels in the hippocampus. The tumor necrosis factor-α levels were significantly decreased by IN insulin both in the cortex and hippocampus. Moreover, IN insulin significantly increased the IL-10 levels in the cortex. The levels of oxidative and nitrosative stress were significantly higher in the LPS-treated mice; however, IN insulin had a modulatory effect on both. LPS significantly increased the antioxidant enzyme activity both in the cortex and hippocampus, whereas IN insulin significantly increased the activity of both superoxide dismutase and catalase in the hippocampus and that of catalase in the cortex. The hydrogen peroxide levels revealed that LPS significantly affected the electron transport chain. Therefore, IN insulin could be useful in the treatment of neuroinflammatory diseases.

Insulin treatment protects the brain against neuroinflammation by reducing cerebral cytokines and modulating mitochondrial function.

In the central nervous system, glial cells protect the brain against neuronal stress by inducing inflammatory responses; namely, intracellular signaling and cytokine production. However, chronic inflammation is often associated with degenerative diseases that can damage hormone signaling and mitochondrial function. Lipopolysaccharide (LPS) induces neuroinflammation by stimulating the production of interleukin-1beta (IL-1ß) and tumor necrosis factor-alpha (TNF-α); moreover, it generates oxidative stress and impairs cognitive functions. The aim of the present study was to assess the therapeutic efficacy of intracerebroventricular (i.c.v.) injections of insulin against neuroinflammation. Inflammation was first induced in male Wistar rats (60 days old, n = 12/group) through an intraperitoneal injection of 0.1 mg/kg LPS. The i.c.v. insulin treatment at a 0.5 mU dose was initiated 4 h later and administered once a day for 5 days. Thereafter, the spatial memory of the rats was assessed, and the hippocampus and cortex were later dissected for biochemical analyses. Our results showed that LPS induced cognitive function impairments, but the insulin treatment reversed these effects. Whereas the levels of brain-derived neurotrophic factor and beta-nerve growth factor in the hippocampus were not altered by LPS, they were decreased in the cortex by insulin. The IL-1ß and TNF-α levels were increased in the cortex and hippocampus following exposure to LPS, but insulin reversed these effects. Evaluation of the H2O2levels and mitochondrial membrane potential revealed that LPS modulated mitochondrial function, an effect that was also reversed by insulin. Moreover, LPS induced oxidative stress by decreasing the superoxide dismutase and catalase activities and glutathione and sulfhydryl levels. Furthermore, the levels of oxidative stress probes/markers (i.e.,2',7'-dichlorodihydrofluoresceindiacetateand nitrite) were higher in the LPS-treated rats. These effects were all reversed in the cortex and hippocampus by insulin treatment. Our results suggest a potential role for insulin as a therapeutic drug against inflammatory diseases associated with mitochondrial dysfunction in the brain.