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Background Verapamil (VER) and cilostazol (Cilo) are mostly used as cardiovascular drugs; they have beneficial effects on different organs toxicities. Aim we investigated whether the Nuclear factor erythroid 2-related factor 2 (Nrf2), Glycogen synthase kinase-3β (GSK-3β), and Nuclear factor-kappa B (NF-κB) pathway involved in the protective role of these drugs against Thioacetamide (TAA) induced hepatotoxicity. Method male rats were randomized divided into five groups, each group (n = 10): control, TAA, VER+TAA, Cilo+TAA, and VER+Cilo+TAA groups. Hepatotoxicity induced in rats by TAA injection once on the 7th day of the experiment. Results TAA-induced hepatotoxicity indicated by a significant elevated in serum markers (Alanine aminotransferases (ALT), Aspartate aminotransferases (AST), and bilirubin), oxidative stress markers (Malondialdehyde (MDA), and Nitric oxide (NO)), and protein levels markers (NF-κB, and S100 calcium-binding protein A4 (S100A4)). Also, TAA decreased Nrf2, and increased GSK-3β genes expression. Histopathological alterations in the liver also appeared as a response to TAA injection. On the other hand VER and/or Cilo significantly prevented TAA-induced hepatotoxicity in rats through significantly decreased in ALT, AST, bilirubin, MDA, NO, NF-κB, and S100A4 protein levels. Also, they increased Nrf2 and decreased GSK-3β genes expression which caused improvement in the histopathological changes of the liver. Conclusion the addition of verapamil to cilostazol potentiated the hepatoprotective activity, and inhibited the progression of hepatotoxicity caused by TAA through the Nrf2/GSK-3β/NF-κBpathway and their activity on oxidative stress, inflammation, and NF-κB protein expression.

Deferasirox belongs to a new is a bishydroxyphenyltriazoles iron chelator used for treatment of chronic iron overload. The use of Deferasirox is associated with hepatotoxicity. Silymarin is a benzo gamma-pyrones flavonoid which affords hepatoprotection and preserves hepatocyte membranes by its antioxidant effect. Curcumin is a poly-phenol compound naturally concentrated in the herb Curcuma longa. The present study was conducted to evaluate and compare the hepatoprotective effects of both silymarin and curcumin against deferasirox-induced hepatotoxicity in rats and to explore the potential mechanisms account for their hepatoprotective effects. The present study was carried out using 32 male wistar randomly assigned into 4 groups (8 rats each) as follows; Group1: served as normal control group in which rats received distilled water (0.5ml per rat) by oral gavage. Group II (Deferasirox group) in which hepatotoxicity was induced by oral administration of deferasirox in a dose of 100 mg/kg once daily for 4 weeks dissolved in distilled water for a concentration of 35mg/ml. Group III (deferasirox+ curcumin) in which rats received curcumin in a dose of 100 mg/kg daily dose by oral gavage for 4 weeks suspended in distilled water for a concentration of 35 mg/ml one hour before administration of deferasirox. Group IV (deferasirox+ silymarin) in which rats received silymarin in dose of 7.56 mg/kg once daily by oral gavage for 4 weeks suspended in distilled water for a concentration of 2.7mg/ml one hour before administration of deferasirox. At the end of the treatment period, all rats were sacrificed by cervical dislocation, blood samples were collected for measurement of ALT, AST, ALP and total bilirubin. Liver samples were used for measurement of MDA, GSH and IL-6. Histopathological and immunohistochemistry were also done. The present data revealed that rats pretreated with curcumin or silymarin exhibited significant reduction in ALT, AST, ALP, total bilirubin, IL-6 and MDA levels with significant elevation of GSH level compared to deferasirox group. In-between group comparison revealed that there was a more significant reduction in ALT, AST, ALP, total bilirubin, IL-6 and MDA in group IV compared to group III. In conclusion, both curcumin and silymarin represent natural protective agents against Deferasirox-induced hepatotoxicity due to their antioxidant and anti-inflammatory effects.

Zaleplon (ZP) is a sedative and hypnotic drug used for the treatment of insomnia. Despite its potent anticonvulsant activity, ZP is not commonly used for the treatment of convulsion since ZP is characterized by its low oral bioavailability as a result of poor solubility and extensive liver metabolism. The following study aimed to formulate specifically controlled release nano‐vehicles for oral and parenteral delivery of ZP to enhance its oral bioavailability and biological activity. A modified single emulsification–solvent evaporation method of sonication force was adopted to optimize the inclusion of ZP into biodegradable nanoparticles (NPs) using poly (dl‐lactic‐co‐glycolic acid) (PLGA). The impacts of various formulation variables on the physicochemical characteristics of the ZP‐PLGA‐NPs and drug release profiles were investigated. Pharmacokinetics and pharmacological activity of ZP‐PLGA‐NPs were studied using experimental animals and were compared with generic ZP tablets. Assessment of gamma‐aminobutyric acid (GABA) level in plasma after oral administration was conducted using enzyme‐linked immunosorbent assay. The maximal electroshock‐induced seizures model evaluated anticonvulsant activity after the parenteral administration of ZP‐loaded NPs. The prepared ZP‐PLGA NPs were negatively charged spherical particles with an average size of 120–300 nm. Optimized ZP‐PLGA NPs showed higher plasma GABA levels, longer sedative, hypnotic effects, and a 3.42‐fold augmentation in oral drug bioavailability in comparison to ZP‐marketed products. Moreover, parenteral administration of ZP‐NPs showed higher anticonvulsant activity compared to free drug. Oral administration of ZP‐PLGA NPs achieved a significant improvement in the drug bioavailability, and parenteral administration showed a pronounced anticonvulsant activity.

Chronic Obstructive Pulmonary Disease (COPD) is a dangerous prevalent smoking-related disease characterized by abnormal inflammation and oxidative stress and expected to be the third cause of death in the world next decade. Corticosteroids have low effects in decreasing numbers of inflammatory mediators specifically in long-term use. Our study designed to investigate the possible protective effects of combined dexamethasone (Dex) (2mg/kg) and losartan (Los) (30mg/kg angiotensin receptor blocker, it possesses antioxidant and anti-inflammatory properties in lung injury in mice) against cigarette -smoke (CS) induced COPD in rats compared with dexamethasone and losartan. Male Sprague Dawley rats (N = 40) divided into five groups (n = 8): control group, CS group, Dex group, Los group, and Dex +Los group. COPD induced in rats by CS exposure twice daily for 10 weeks. After the specified treatment period, bronchoalveolar lavage fluid (BALF) and lung tissue were collected for measurement of SOD, NO, MDA, ICAM-, MMP-9, CRP, NF-κB and histopathology scoring. Our results indicated that Los+Dex significantly prevent CS-induced COPD emphysema, congested alveoli, and elevation of lung injury parameters in BALF. They also showed a significant decrease in MDA, ICAM-1, MMP-9, CRP, and NF-κB and a significant increase in SOD and NO. In conclusion, adding Los to Dex potentiating their activity in inhibition the progression of COPD based on its activity on oxidative stress, inflammation, and NF-κB protein expression.

A relationship between Microbiome and its effect on depression has been suspected in earlier studies. Here we examined whether the addition of Lactobacillus probiotics which flourishes the gut-microbiota will have a beneficial adjuvant therapeutic effect on treatment of depression or even considering it as a main treatment line in the future for treatment of depression or anxiety like behavior after further studies. Mice receiving probiotics in their diet exhibited mostly similar anxiolytic and anti-depressive effects of the mice that received SSRI anti-depressant citalopram and displayed enhanced outcomes which were shown in the Tail Suspension test – which is considered a high output tool in assessing anti-depression medications –, Super oxidase dismutase concentration in the brain tissue and HPLC analysis of Kynurenine biomarker in the brain. Taken together these data support the link between healthy gut microbiome and its effect on depression-like behavior and suggest that probiotics may even have a similar therapeutic effect of anti- depressants in treatment of depression. Keywords: Probiotics, Depression, Gut-microbiota, Citalopram

The implications of oxidative stress and neuro-inflammation in the pathogenesis of schizophrenia have been elucidated. Despite their effectiveness against positive symptoms of schizophrenia, antipsychotics have limited effectiveness against negative and cognitive symptoms and are associated with remarkable adverse effects. The use of celecoxib or omega-3 in schizophrenia may have beneficial effects. This study aimed to evaluate the possible efficacies of celecoxib, omega-3 or the combination of celecoxib+risperidone and omega-3+ risperidone compared to risperidone on the behavior and brain biochemistry in rats. In the present study, an amphetamine-induced model of schizophrenia in adult male rats was used to evaluate the effects of celecoxib, omega-3, celecoxib+risperidone and omega-3+ risperidone on the behavior of animals and on brain lipid peroxidation or tumor necrosis factor-alpha. In the water maze task, celecoxib, omega-3, celecoxib+risperidone, omega-3+ risperidone significantly decreased the latency time compared to amphetamine-treated group. Celecoxib, omega-3, celecoxib+risperidone, omega-3+risperidone also significantly reversed the decreased spontaneous alternation induced by amphetamine in the Y-maze task. In the social interaction task, groups treated with celecoxib, omega-3, celecoxib+risperidone, omega-3+ risperidone spent less time to recognize foreign animals than animals in the amphetamine-treated group. Increased brain MDA and TNF-α levels due to amphetamine were significantly reduced in groups treated with celecoxib+risperidone or omega-3+ risperidone. The present findings showed that celecoxib or omega-3 can attenuate amphetamine- induced behavioral impairment and these effects may be associated with their ability to decrease lipid peroxidation and cytokine release. Celecoxib or omega-3 may be promising candidates as adjuvant therapy for schizophrenia.