Therapeutic Effects of Thymoquinone on Alzheimer's Disease through Modulating Amyloid-beta Neurotoxicity and Neuro-inflammatory Cytokine Levels.

Alzheimer's disease (AD) is a neurodegenerative disease that involves several impaired neuronal pathways. Modulating the amyloid-beta (ß-amyloid) system is being tested to treat AD. Amyloid-beta neurotoxicity is associated with neuroinflammation and plaque formation, further progressing to AD. Protecting neurons from ß-amyloid neurotoxicity could be an efficient strategy for the treatment of AD. Thymoquinone (TQ) is an active ingredient in Nigella sativa (NS) and has shown effective therapeutic properties in AD models. TQ was able to attenuate the behavioral dysfunctions in AD models. Moreover, TQ could attenuate the neuroinflammation properties in animals with AD. In addition, studies have shown that TQ could modulate ß -amyloid neurotoxicity, an effect associated with improved AD behavioral symptoms. In this review, we highlighted the therapeutic effects of TQ on the progression of AD through modulating ß-amyloid neurotoxicity and neuro-inflammatory cytokine levels. Other phenolic compounds also present in NS improved behavioral and neuronal impairments in AD models, supporting TQ's anti-Alzhiemer's efficacy.

Nicotine and cotinine quantification after a 4-week inhalation of electronic cigarette vapors in male and female mice using UPLC-MS/MS.

OBJECTIVES: To detect the cotinine and nicotine serum concentrations of female and male C57BL/6J mice after a 4-week exposure to electronic (e)-cigarette vapors using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). METHODS: This experimental study was carried out at an animal facility and laboratories, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia, between January and August 2020. A 4-week exposure to e-cigarettes was carried out using male and female mice and serum samples were obtained for cotinine and nicotine quantification using UPLC-MS/MS. The chromatographic procedures involved the use of a BEH HSS T3 C18 column (100 mm x 2.1 mm, 1.7 µm) with acetonitrile as a mobile phase and 0.1% formic acid (2:98 v/v). RESULTS: The applied methodology has highly efficient properties of detection, estimation, and extraction, where the limit of quantification (LOQ) for nicotine was 0.57 ng/mL and limit of detection (LOD) for nicotine was 0.19 ng/mL, while the LOQ for cotinine was 1.11 ng/mL and LOD for cotinine was 0.38 ng/mL. The correlation coefficient was r2>0.99 for both compounds. The average recovery rate was 101.6±1.33 for nicotine and 100.4±0.54 for cotinine, while the precision and accuracy for cotinine and nicotine were less than 6.1. The serum cotinine level was higher in males (433.7±19.55) than females (362.3±16.27). CONCLUSION: This study showed that the gender factor might play a crucial role in nicotine metabolism.

Elucidation of the Molecular Mechanisms Underlying Sorafenib-Induced Hepatotoxicity.

Sorafenib is a small, orally-active multikinase inhibitor that is most frequently used for the management of renal cell carcinoma, hepatocellular carcinoma, and radioactive iodine-resistant thyroid carcinoma. However, recent reports have associated sorafenib with hepatotoxicity that can limit its clinical application, although the mechanism of hepatotoxicity is still to be elucidated. Thus, our study was designed to explore the molecular mechanisms underlying sorafenib-induced hepatotoxicity in an in vivo model. Twenty male adult Wistar rats were randomly placed into two groups; the first group received an oral dose of normal saline (vehicle), and the second received sorafenib (30 mg/kg) once daily for twenty-one consecutive days. After twenty-one days, liver tissues and blood samples were used for gene expression, protein expression, and biochemical analysis. Sorafenib treatment resulted in markedly increased levels of alanine aminotransferase and alkaline phosphatase, which indicate the presence of liver damage. Additionally, sorafenib administration induced the inflammatory and oxidative stress marker NF-κB-p65, while antioxidant enzymes were attenuated. Moreover, sorafenib caused upregulation of both gene and protein for the apoptotic markers cleaved Caspase-3, Bax, and Bid, and downregulation of the antiapoptotic protein Bcl-2. In conclusion, our findings suggest that sorafenib administration is associated with hepatotoxicity, which might be due to the activation of oxidative stress and apoptotic pathways.