Rationale
Exposure to UV light can induce adverse effects on human health, such as photo‐aging, immunosuppression, and cancer. Sunscreens are used to prevent the absorption of UV rays, but certain UV‐filtering compounds have been shown to disrupt endocrine systems or act as carcinogens. To assess the effects of the exposure to such compounds, it is important to study the pathways by which they are biotransformed in the body.
Methods
Liquid chromatography coupled to high‐resolution tandem mass spectrometry (LC/HRMS/MS) was employed to evaluate the oxidative metabolism and, specifically, the formation of reactive metabolites of six active ingredients commonly used in sunscreen formulations: oxybenzone, avobenzone, homosalate, octisalate, octocrylene, and octinoxate. In vitro incubations were performed with human and rat liver microsomes in the presence of β‐nicotinamide adenine dinucleotide phosphate and glutathione. An LC/HRMS/MS method was developed to identify metabolites employing a biphenyl reversed‐phase column for separating parent molecules, metabolites, and glutathione (GSH) adducts.
Results
Each tested compound resulted in the formation of several metabolites, including at least one GSH adduct. Compounds containing ester groups were hydrolyzed, and some metabolites of the free acid forms were also detected. High‐resolution MS/MS data was crucial for the structural elucidation of metabolites and GSH adducts. Fragmentation pathways were proposed for all parent compounds, as well as each described metabolite and adduct.
Conclusions
The results of this study will help better understand the metabolism and detoxification pathways of these xenobiotics.
Vitamin D (VD) cannot be considered as a true vitamin, but rather as a hormone, which exerts its action via a vitamin D receptor (VDR). Many genes have been shown to be involved in the evolution of diabetes in various populations, such as the vitamin D receptor gene. The aim of our study was to investigate if BsmI, TaqI, ApaI, FokI, and Tru9I, polymorphisms of VDR gene have an impact on MODY diabetes and its clinical aspects in a Tunisian population. A total of 95 patients and 153 controls were genotyped using PCR-RFLP. The comparison of the allelic and genotypic frequencies of the five polymorphisms between MODY subjects and control groups revealed the association of MODY diabetes with TaqI, Tru9I and BsmI polymorphisms and no significant differences were observed in the distributions for the ApaI and FokI polymorphisms. After stratification with biochemical and clinical parameters and TaqI, Tru9I and BsmI polymorphisms, we found an association between the three SNPs and different parameters such as age of diagnosis, therapy, hsCRP and HDL-C levels. Our results revealed that TaqI, Tru9I and BsmI polymorphisms may be more related to the progression of MODY diabetes. The possible role of vitamin D in the pathogenesis of MODY is far from being completely understood. Further knowledge on this issue may identify new candidate targets in the treatment and prevention of the disease. Our findings suggest that the TaqI, Tru9I and BsmI polymorphisms may be more related to the progression of MODY diabetes.
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