Efficacy of Albendazole-Chitosan Microsphere-based Treatment for Alveolar Echinococcosis in Mice

This study aimed to investigate the pharmacology and anti-parasitic efficacy of albendazole–chitosan microspheres (ABZ-CS-MPs) for established intraperitoneal infections of Echinococcus multilocularis metacestodes in an experimental murine model. Male outbred Kunming mice infected with E. multilocularis Metacestodes were administered with three ABZ formulations, namely, ABZ-CS-MPs, Liposome–Albendazole (L-ABZ), and albendazole tablet (ABZ-T). Each of the ABZ formulations was given orally at three different doses of 37.5, 75, and 150mg/kg, three times a week for 12 weeks postinfection. After administering the drugs, we monitored the pharmacological performance and anti-parasitic efficacy of ABZ-CS-MPs compared with L-ABZ, and ABZ-T treated mice. ABZ-CS-MPs reduced the weight of tissues containing E. multilocularis metacestodes most effectively compared with the ABZ-T group and untreated controls. Metacestode grown was Highly suppressed during treatment with ABZ-CS-MPs. Significantly higher plasma levels of ABZ metabolites were measured in mice treated with ABZ-CS-MPs or L-ABZ compared with ABZ-T. In particular, enhanced ABZ-sulfoxide concentration profiles were observed in the mice given 150mg/kg of ABZ-CS-MPs, but not in the mice treated with L-ABZ. Histological examination showed that damages caused disorganization of both the germinal and laminated layers of liver hyatid cysts, demolishing their characteristic structures after treatment with ABZ-CS-MPs or L-ABZ. Over time, ABZ-CS-MPs treatment induced a shift from Th2-dominant to Th1-dominant immune response. CS-MPs As a new carrier exhibited improved absorption and increased bioavailability of ABZ in the treatment of E. multilocularis infections in mice.     

Sesamin attenuates behavioral,biochemical and histological alterations induced by reversible middle cerebral artery occlusion in the rats

Restoration of blood flow to an ischemic brain region is associated with generation of reactive oxygen species (ROS) with consequent reperfusion injury. ROS cause lipid peroxidation, protein oxidation, and DNA damage, all of which are deleterious to cells. So diminishing the production of free radicals and scavenging them may be a successful therapeutic strategy for the protection of brain tissue in cerebral stroke. The present study investigated the neuroprotective effect of sesamin (Sn) to reduce brain injury after middle cerebral artery occlusion (MCAO). The middle cerebral artery (MCA) of adult male Wistar rat was occluded for 2 h and reperfused for 22 h. Sesamin is the most abundant lignan in sesame seed oil is a potent antioxidant. Sesamin (30 mg/kg) was given orally twice, 30 min before the onset of ischemia and 12 h after reperfusion. The initial investigations revealed that sesamin reduced the neurological deficits in terms of behavior and reduced the level of thiobarbituric acid reactive species (TBARS), and protein carbonyl (PC) in the different areas of the brain when compared with the MCAO group. A significantly depleted level of glutathione and its dependent enzymes (glutathione peroxidase [GPx] and glutathione reductase [GR]) in MCAO group were protected significantly in MCAO group treated with sesamin. The present study suggests that sesamin may be able to attenuate the ischemic cell death and plays a crucial role as a neuroprotectant in regulating levels of reactive oxygen species in the rat brain. Thus, sesamin may be a potential compound in stroke therapy.     

Quercetin Protects Against Oxidative Stress Associated Damages in a Rat Model of Transient Focal Cerebral Ischemia and Reperfusion

Experimental studies have demonstrated that oxidative stress and apoptosis play an important role in cerebral ischemic pathogenesis and may represent a target for treatment. The purpose of this study was to determine whether the quercetin dihydrate (Q) protects against cerebral ischemia neuronal damage. Male Wistar rats were subjected to transient middle cerebral artery occlusion (MCAO) for 2?h and reperfused for 72?h. Quercetin (30?mg/kg, i.p) was administrated 30?min before the onset of ischemia and after the ischemia at interval of 0, 24, 48, and 72?h. The administration of Q showed marked reduction in infarct size, reduced the neurological deficits in terms of behaviors, suppressed neuronal loss and diminished the p53 expression in MCAO rats. Q was found to be successful in upregulating the antioxidant status and lowering the TBARS level. Conversely, the elevated activity of poly (ADP-ribose) polymerase (PARP), and activity of caspase-3 in MCAO group was attenuated significantly in Q treated group when compared with MCAO group. Our study reveals that Q, as a powerful antioxidant, could prevent free radicals associated oxidative damage and morphological changes in the MCAO rats. Thus, it may have a therapeutic value for the treatment of stroke.     

Modulation of restraint stress induced oxidative changes in rats by antioxidant vitamins

In the present study we examined immobilization stress-induced antioxidant defense changes in rat plasma and also observed the antioxidant effects of pre and post vitamins A, E and C administration (15 mg/Kg of body weight) individually and in combination (vit E + C) on these alterations.Following immobilization stress the circulating activities of superoxide dismutase, catalase and glutathione-S-transferase were decreased, while the level of thiobarbituric acid reactive substances (TBARS) was increased as compared to non-stressed control rats.Post treatment with individual vitamins A, E and C (after exposure to stress) resulted in a less marked alteration of plasma TBARS levels and activities of SOD, GST and catalase as compared to pre vitamin stress or stress alone treatments. Both pre and post vitamin treatments were effective in preventing stress induced derangement of free radical metabolism with a relative dominance by latter. The combined treatment with vitamin E and C did not show any additive antioxidant effect on restraint stress induced altered free radical metabolism, rather a predominant effect similar to vitamin E alone was observed. The prevention of oxidative stress generated in response to restraint stress by the vitamins can be summarized as: vitamin (E + C) i.e. vit E > vit C > vit A, thus combined vitamin (E + C) treatment though showed maximum preventive effect, but was similar to vitamin E treatment alone, in terms of the circulating activities of SOD, GST, catalase and TBARS levels.     

Comparative analysis of realistic CT-scan and simplified human airway models in airflow simulation

Efforts to model the human upper respiratory system have undergone many phases. Geometrical proximity to the realistic shape has been the subject of many research projects. In this study, three different geometries of the trachea and main bronchus were modelled, which were reconstructed from computed tomography (CT) scan images. The geometrical variations were named realistic, simplified and oversimplified. Realistic refers to the lifelike image taken from digital imaging and communications in medicine format CT scan images, simplified refers to the reconstructed image based on natural images without realistic details pertaining to the rough surfaces, and oversimplified describes the straight wall geometry of the airway. The characteristics of steady state flows with different flow rates were investigated, simulating three varied physical activities and passing through each model. The results agree with previous studies where simplified models are sufficient for providing comparable results for airflow in human airways. This work further suggests that, under most exercise conditions, the idealised oversimplified model is not favourable for simulating either airflow regimes or airflow with particle depositions. However, in terms of immediate analysis for the prediction of abnormalities of various dimensions of human airways, the oversimplified techniques may be used.     

Neuroprotective Effect of Sesame Seed Oil in 6-Hydroxydopamine Induced Neurotoxicity in Mice Model: Cellular,Biochemical and Neurochemical Evidence

Natural antioxidants have shown a remarkable reduction in oxidative stress due to excess formation of reactive oxygen species by enhancing antioxidant mechanism in the neurodegenerative disorders. Sesame seed oil (SO) is one of the most important edible oil in India as well as in Asian countries and has potent antioxidant properties thus the present study evaluated the neuroprotective effect of SO by using 6-Hydroxydopamine (6-OHDA)-induced Parkinson’s disease model in mice. The mice were fed an SO mix diet for 15 days and then 6-OHDA was injected into the right striatum of mice brain. Three weeks after 6-OHDA infusion, mice were sacrificed and the striatum was removed. The neuroprotective role of SO on the activities of antioxidant and non-antioxidant enzymes such as glutathione reductase (GR), glutathione-S-transferase (GST), glutathione peroxidase (GPx), catalase (CAT) and content of glutathione (GSH) and thiobarbituric acid reactive substance (TBARS) were studied in the striatum. The activities of all the above-mentioned enzymes decreased significantly in 6-OHDA group (Lesioned) when compared with Sham. The pretreatment of SO on antioxidant mechanism and dopamine level in the brain had shown some significant improvement in Lesion+SO (L+SO) group when compared with Lesioned group. However, NADPH oxidase subunit, Nox2 and inflammatory stimulator Cox2 expression was increased as well as antioxidant MnSOD level was decreased in Lesioned group while SO showed the inhibitory effect on the activation of Nox2 and Cox2 and restored MnSOD expression in L+SO group. Increased tyrosine hydroxylase (TH) expression in substantia nigra as well as dopamine and its metabolite DOPAC level in L+SO group also support our findings that SO may inhibit activation of NADPH oxidase dependent inflammatory mechanism due to 6-OHDA induced neurotoxicity in mice.     

Untargeted Plasma Metabolomics Identifies Endogenous Metabolite with Drug-like Properties in Chronic Animal Model of Multiple Sclerosis

We performed untargeted metabolomics in plasma of B6 mice with experimental autoimmune encephalitis (EAE) at the chronic phase of the disease in search of an altered metabolic pathway(s). Of 324 metabolites measured, 100 metabolites that mapped to various pathways (mainly lipids) linked to mitochondrial function, inflammation, and membrane stability were observed to be significantly altered between EAE and control (p < 0.05, false discovery rate <0.10). Bioinformatics analysis revealed six metabolic pathways being impacted and altered in EAE, including α-linolenic acid and linoleic acid metabolism (PUFA). The metabolites of PUFAs, including ω-3 and ω-6 fatty acids, are commonly decreased in mouse models of multiple sclerosis (MS) and in patients with MS. Daily oral administration of resolvin D1, a downstream metabolite of ω-3, decreased disease progression by suppressing autoreactive T cells and inducing an M2 phenotype of monocytes/macrophages and resident brain microglial cells. This study provides a proof of principle for the application of metabolomics to identify an endogenous metabolite(s) possessing drug-like properties, which is assessed for therapy in preclinical mouse models of MS.