Ginger Extract Loaded into Chitosan Nanoparticles Enhances Cytotoxicity and Reduces Cardiotoxicity of Doxorubicin in Hepatocellular Carcinoma in Mice.

This study aimed to investigate the impact of ginger extract (GE) loaded into chitosan nanoparticles (CNPs) in enhancing cytotoxicity and reducing cardiotoxicity of doxorubicin (DXN) in hepatocellular carcinoma (HCC) induced mice. DXN and GE were loaded into CNPs and cytotoxicity of loaded and unloaded drugs against HepG2 cells was evaluated. HCC was induced in male albino mice by injection of diethylnitrosamine (DINA). Mice were divided into eight groups (n = 15): (1) normal control, (2) DINA, (3) CNPs, (4) free DXN, (5) CNPs DXN, (6) free GE, (7) CNPs GE, and (8) CNPs DXN + CNPs GE. Both GE and DXN loaded into CNPs showed a greater decline in cell viability of HepG2 cells than the unloaded forms. GE CNPs displayed pronounced anticancer activity In Vivo through apoptosis, greater down-regulation of multidrug resistance 1, enhancement of anti-oxidant activity and depletion of vascular endothelial growth factor content in liver tissues. GE CNPs in combination with DXN CNPs showed nearly normal hepatic lobule architecture and the greatest increase in apoptotic cell count. Co-treatment group had decreased cardiac malondialdehyde, tumor necrosis factor-α and serum activity of creatine kinase and lactate dehydrogenase. Combination of GE CNPs and DXN CNPs might be a potentially effective therapeutic approach for HCC.

Protective Effects of Combined Selenium and Punica granatum Treatment on Some Inflammatory and Oxidative Stress Markers in Arsenic-Induced Hepatotoxicity in Rats.

Oxidative stress is one of the major mechanisms implicated in inorganic arsenic poisoning. Punica granatum is known by its free radical scavenging properties. The aim of this study was to evaluate the protective role of combined selenium and P. granatum against arsenic-induced liver injury. Seventy-five female albino rats were divided into five groups (of 15 rats each). Toxicity was induced by oral sodium arsenite (5.5 mg/kg body weight (bw) daily) (group ІІ). Treatment of arsenic-intoxicated rats was induced by daily oral administration of sodium selenite (3 mg/kg bw) (group ІІІ), 100 mg of P. granatum ethanol extract per kilogram body weight dissolved in 300 mL distilled water in three divided doses (100 mL of this suspension every 8 h) (group IV), and combined daily oral treatment with both selenite and P. granatum ethanol extract (group V). After 3 weeks, serum and liver tissues were obtained from the decapitated rats for different estimations. Hepatotoxicity was demonstrated by significant elevation in liver weights and activities of liver enzymes, alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and decrease in serum total proteins and albumin (p < 0.05) which were confirmed by histopathological examination. Additionally, arsenic hepatotoxicity led to an increased values of malondialdehyde, advanced oxidation protein products, nitric oxide, and interleukin-6 (IL-6) (p < 0.05) and decreased activity of thioredoxin reductase, values of total anti-oxidant capacity, and nuclear factor erythroid 2-related factor 2 (Nrf2) gene expression. Significant improvement in all assessed parameters was observed in rat group treated with both P. granatum and selenium. It was concluded that combined P. granatum and selenium treatment had a synergistic hepatoprotective effect against arsenic toxicity through activation of Nrf2 anti-oxidant pathway.

Favorable effects of vildagliptin on metabolic and cognitive dysfunctions in streptozotocin-induced diabetic rats.

Progression of diabetes mellitus is accompanied by metabolic disorders together with psychological deficits including cognitive dysfunctions. Herein, we used a murine streptozotocin (STZ)-induced diabetes to investigate the beneficial effects of vildagliptin not only on metabolic abnormalities, but also on diabetes-induced cognitive decline. Sixty rats were divided randomly and equally into 2 groups; one remains normal and the other serves as STZ- induced diabetic. Both groups were further divided equally into 2 groups; one received vehicle and the other received oral vildagliptin for 8 weeks. Cognitive behavior was assessed using novel object recognition test. Blood samples were collected to measure metabolic parameters and dipeptidyl peptidase (DPP)-IV activity. Brains were removed and investigated for the levels of inflammatory and oxidative stress markers malondialdehyde (MDA), superoxide dismutase (SOD) and tumor necrosis factor-α (TNF-α), in addition to brain-derived neurotrophic factor (BDNF) and relative expression of nuclear factor kappa B (NF-κB)/p65. Treatment of STZ-induced diabetic rats with vildagliptin increased their body weight and corrected diabetes-induced memory and learning impairment. Moreover, vildagliptin significantly decreased serum levels of glucose and lipids (except high density lipoprotein) together with brain MDA, TNF-α, serum DPP-IV activities and NF-κB/p65 gene expression. On the other hand, vildagliptin significantly increased brain BDNF, SOD as well as serum insulin. Results suggested that vildagliptin has a protective role in counteracting both metabolic abnormalities and memory deficits in diabetic rats, possibly via its anti-hyperglycemic, anti-inflammatory, antioxidant effects, together with reduction of brain NF-κB/p65 over expression.