Stigmasterol (99.9% pure) was isolated from Azadirachta indica and its chemopreventive effect on 7,12-dimethylbenz[a]anthracene (DMBA)-induced skin cancer was investigated in Swiss albino mice. Skin tumors were induced by topical application of DMBA and promoted by croton oil. To assess the chemopreventive potential of stigmasterol, it was orally administered at a concentration of 200 mg/kg and 400 mg/kg three times weekly for 16 weeks. Reduction in tumor size and cumulative number of papillomas were seen as a result of treatment with stigmasterol. The average latency period was significantly increased as compared with the carcinogen-treated control. Stigmasterol induced a significant decrease in the activity of serum enzymes, such as aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and bilirubin as compared with the control. Stigmasterol significantly increased glutathione, superoxide dismutase, and catalase as compared with the control. Elevated levels of lipid peroxide and DNA damage in the control group were significantly inhibited by administration of stigmasterol. From the present study, it can be inferred that stigmasterol has chemopreventive activity in an experimental model of cancer. This chemopreventive activity may be linked to the oxidative stress of stigmasterol. The antigenotoxic properties of stigmasterol are also likely to contribute to its chemopreventive action.

No abstract

Nanotechnology has the capacity to revolutionize numerous fields and processes, however, exposure-induced health effects are of concern. The majority of nanoparticle (NP) safety evaluations have been performed utilizing healthy models and have demonstrated the potential for pulmonary toxicity. A growing proportion of individuals suffer diseases that may enhance their susceptibility to exposures. Specifically, metabolic syndrome (MetS) is increasingly prevalent and is a risk factor for the development of chronic diseases including type-2 diabetes, cardiovascular disease, and cancer. MetS is a combination of conditions which includes dyslipidemia, obesity, hypertension, and insulin resistance. Due to the role of lipids in inflammatory signaling, we hypothesize that MetS-associated dyslipidemia may modulate NP-induced immune responses. To examine this hypothesis, mice were fed either a control diet or a high-fat western diet (HFWD) for 14-weeks. A subset of mice were treated with atorvastatin for the final 7-weeks to modulate lipids. Mice were exposed to silver NPs (AgNPs) via oropharyngeal aspiration and acute toxicity endpoints were evaluated 24-h postexposure. Mice on the HFWD demonstrated MetS-associated alterations such as increased body weight and cholesterol compared to control-diet mice. Cytometry analysis of bronchoalveolar lavage fluid (BALF) demonstrated exacerbation of AgNPinduced neutrophilic influx in MetS mice compared to healthy. Additionally, enhanced proinflammatory mRNA expression and protein levels of monocyte chemoattractant protein-1, macrophage inflammatory protein-2, and interleukin-6 were observed in MetS mice compared to healthy following exposure. AgNP exposure reduced mRNA expression of enzymes involved in lipid metabolism, such as arachidonate 5lipoxygenase and arachidonate 15-lipoxygenase in both mouse models. Exposure to AgNPs decreased inducible nitric oxide synthase gene expression in MetS mice. An exploratory lipidomic profiling approach was utilized to screen lipid mediators involved in pulmonary inflammation. This assessment indicates the potential for