Eugenol attenuates TiO2 nanoparticles-induced oxidative damage, biochemical toxicity and DNA damage in Wistar rats: an in vivo study.

Titanium dioxide nanoparticles (TiO2 NPs) are widely used in food, edible dyes, and other commercial products. Human exposure to TiO2 NPs has raised concerns regarding their toxic potential. Various studies have evaluated the TiO2 NPs-induced toxicity, oxidative damage to the cellular components, and genotoxicity. In the present study, we examined whether co-treatment with the dietary antioxidant eugenol can attenuate or protect against TiO2 NPs-induced toxicity. We exposed the adult male Wistar rats to TiO2 NPs (150 mg/kg body weight) by intraperitoneal injection (i.p.) either alone or as co-treatment with eugenol (1-10 mg/kg body weight) once a day for 14 days. The untreated rats were supplied saline and served as control. Titanium (Ti) accumulation in various tissues was analyzed by inductively coupled plasma mass spectrometry. Serum levels of liver and kidney biomarkers and oxidative stress markers in the liver, kidney, and spleen were determined. A significant increase in hydrogen peroxide level confirmed that oxidative stress occurred in these tissues. TiO2 NPs induced oxidation of lipids, and decreased glutathione level and antioxidant enzyme activity in the kidney, liver, and spleen of treated rats. TiO2 NPs also increased the serum levels of alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, albumin, and total cholesterol and decreased the blood urea nitrogen, uric acid, and total bilirubin in serum, which indicates oxidative damage to the liver and kidney. In eugenol and TiO2 NPs co-treated rats, all these changes were mitigated. Single-cell gel electrophoresis (comet assay) of lymphocytes showed longer comet tail length in TiO2 NPs-treated groups, indicating DNA damage while tail length was reduced in eugenol and TiO2 NPs co-treated groups. Thus, it seems that eugenol can be used as a chemoprotective agent against TiO2 NPs-induced toxicity.

Targeted next-generation sequencing reveals novel and known variants of thrombophilia associated genes in Saudi patients with venous thromboembolism.

BACKGROUND: Thrombophilia is a substantial source of indisposition and mortality in several countries, including Arab populations. Deep venous thrombosis (DVT) with or without pulmonary embolism (PE) is the prevalent clinical manifestation of thrombophilia. While many genetic risk factors for DVT are known, almost all associated with hemostasis, many genetic factors remain unexplained. Nowadays, Next Generation Sequencing (NGS) offers a potential solution that allows several candidate genes to be analyzed simultaneously at a reasonable expense. METHODS: We performed variant screening in the thrombophilia associated genes in Factor V Leiden (FVL) mutation-negative patients using Ion Torrent Next-generation sequencing (NGS). Ion AmpliSeq panel for 18 genes was designed. Twenty-nine unrelated patients with idiopathic VTE were recruited for NGS. RESULTS: We were able to identify 19 variants (1 novel and 18 previously reported) in 10 out of 18 targeted genes. Pathogenic variants were identified in 22 patients demonstrating mutation detection rates of 76%. Previously reported variants in the F5, MTHFR, PROS1, PROC, F8, F9, SERPINA10, SERPIND1, and HRG genes were recognized in 21 patients. More than one variant in the targeted genes was detected in some of the patients with VTE. We identified SERPINA10 recurrent variant p.(R88*) in seven patients representing 32% of VTE cases. Additionally, we report one novel variant c.356G > T, p.(G119V) in the F7 gene, considered to be pathogenic in this study. CONCLUSIONS: Our studies finding illustrates the ability of targeted next-generation sequencing to uncover uncommon/unknown genetic variants that may predispose to thrombophilia. The finding of the novel variant in the F7 gene extends the spectrum of variants affecting thrombosis. While a comparatively small number of subjects have been included in our cohort, the findings summarize the possible genetic features of thrombophilia.

The dual clastogenic and anti-clastogenic properties of quercetin is dose dependent.

Iron is a ubiquitous constituent of cytochromes, oxygen-binding molecules and a variety of enzymes because of its property to transition from ferric (Fe3+) to ferrous (Fe2+) state, leading to change in the redox potential. However, the same property accounts for free radical injury. In order to overcome harmful effects of iron we investigated the possible protective effect of quercetin (QCT), a flavonoid with antioxidant property, against the oxidative DNA damage caused by iron sulfate in vivo. We show that QCT exerts efficient anticlastogenic action in the context of iron sulfate treatment up to a dose of 500 mg/kg while it induces DNA damage at higher doses. These findings show that QCT has a dual effect; at low doses it ameliorates the oxidative damage produced by iron, and it is genotoxic and cytotoxic at a higher dose.