Long-term exposure to xenoestrogens alters some brain monoamines and both serum thyroid hormones and cortisol levels in adult male rats

AbstractThe present study was designed to examine the effect of long-term treatment with the phytoestrogen soy isoflavone [(SIF); 43mg/kg body weight/day] and/or the plastics component bisphenol-A [(BPA); 3mg/kg body weight/day] on some monoamines in the forebrain and both serum thyroid hormones and cortisol levels of adult rats. Significant increases in serotonin (5-HT) and norepinephrine (NE) level, and significant decreases in 5-hydroxyindoleacetic acid (5-HIAA) level and 5-HIAA/5-HT ratio, were observed after treatment with SIF or BPA. Level of dopamine (DA) was increased in SIF-treated group and decreased in BPA-treated group. Activity of monoamine oxidase (MAO) was decreased in all treated groups. The level of serum thyroid hormones (fT3 and fT4) was increased after treatment with SIF and decreased after exposure to BPA, while cortisol level was increased in all treated groups. It may be concluded that long-term exposure to SIF or BPA disrupts monoamine levels in the forebrain of adult rats through alteration in the metabolic pathways of amines and disorders of thyroid hormones and cortisol levels

Anti-hepatotoxic effect of Casuarina stricta and Casuarina suberosa extracts on alcohol-induced liver toxicity in rats

In recent years, there has been a global trend toward the use of natural phytochemicals present in natural resources, such as fruits, vegetables, oilseeds, and herbs, as antioxidants and functional foods. The aim of the present study was to investigate the protective and antioxidant effects of methanolic extract of Casuarina stricta and Casuarina suberosa leaves on ethanol induced hepatotoxicity in rats. The ethanol intoxication (1 ml of 40 % ethanol for 100 gm body weight for 6 weeks) to rats resulted in a significant increase in serum ALT, AST, \u3b3 glutamyl transferase (\u3b3 GT), hydroxyproline, MDA level and a significant decrease in serum albumin, total protein, A/G ratio, total antioxidant capacity, SOD, catalase activities and GSH level, P < 0.05. The treatment with Casuarina stricta and Casuarina suberosa extract at a dose of 250 mg/Kg body weight together with ethanol for 6 weeks successfully prevented the alterations of studied parameters in the treated groups. Both extracts significantly increased the total antioxidant capacity. The experimental results indicate that, both Casuarina extracts have excellent hepatoprotective effect

Development of canagliflozin nanocrystals sublingual tablets in the presence of sodium caprate permeability enhancer: formulation optimization, characterization, in-vitro, in silico, and in-vivo study

AbstractCanagliflozin (CFZ) is a sodium-glucose cotransporter-2 inhibitor (SGLT2) that lowers albuminuria in type-2 diabetic patients, cardiovascular, kidney, and liver disease. CFZ is classified as class IV in the Biopharmaceutical Classification System (BCS) and is characterized by low permeability, solubility, and bioavailability, most likely attributed to hepatic first-pass metabolism. Nanocrystal-based sublingual formulations were developed in the presence of sodium caprate, as a wetting agent, and as a permeability enhancer. This formulation is suitable for children and adults and could enhance solubility, permeability, and avoid enterohepatic circulation due to absorption through the sublingual mucosa. In the present study, formulations containing various surfactants (P237, P338, PVA, and PVP K30) were prepared by the Sono-homo-assisted precipitation ion technique. The optimized formula prepared with PVP-K30 showed the smallest particle size (157 ± 0.32 nm), Zeta-potential (−18 ± 0.01), and morphology by TEM analysis. The optimized formula was subsequently formulated into a sublingual tablet containing Pharma burst-V® with a shorter disintegration time (51s) for the in-vivo study. The selected sublingual tablet improved histological and biochemical markers (blood glucose, liver, and kidney function), AMP-activated protein kinase (AMPK), and protein kinase B (AKT) pathway compared to the market formula, increased CFZ’s antidiabetic potency in diabetic rabbits, boosted bioavailability by five-fold, and produced faster onset of action. These findings suggest successful treatment of diabetes with CFZ nanocrystal-sublingual tablets