Assessment of genotoxicity biomarkers in gasoline station attendants due to occupational exposure.

Gasoline station attendants are exposed to numerous chemicals that might have genotoxic and carcinogenic potential, such as benzene in fuel vapor and particulate matter and polycyclic aromatic hydrocarbons in vehicle exhaust emission. According to IARC, benzene and diesel particulates are Group 1 human carcinogens, and gasoline has been classified as Group 2A "possibly carcinogenic to humans." At gas stations, self-service is not implemented in Turkey; fuel-filling service is provided entirely by employees, and therefore they are exposed to those chemicals in the workplace during all working hours. Genetic monitoring of workers with occupational exposure to possible genotoxic agents allows early detection of cancer. We aimed to investigate the genotoxic damage due to exposures in gasoline station attendants in Turkey. Genotoxicity was evaluated by the Comet, chromosomal aberration, and cytokinesis-block micronucleus assays in peripheral blood lymphocytes. Gasoline station attendants (n = 53) had higher tail length, tail intensity, and tail moment values than controls (n = 61). In gasoline station attendants (n = 46), the frequencies of chromatid gaps, chromosome gaps, and total aberrations were higher compared with controls (n = 59). Increased frequencies of micronuclei and nucleoplasmic bridges were determined in gasoline station attendants (n = 47) compared with controls (n = 40). Factors such as age, duration of working, and smoking did not have any significant impact on genotoxic endpoints. Only exposure increased genotoxic damage in gasoline station attendants independently from demographic and clinical characteristics. Occupational exposure-related genotoxicity risk may increase in gasoline station attendants who are chronically exposed to gasoline and various chemicals in vehicle exhaust emissions.

Oxidative stress gene polymorphisms may have an impact in the development of ischemic stroke.

BACKGROUND: Antioxidants are responsible for detoxification of harmful effects of reactive oxygen species. Genetic factors may influence antioxidant activity as a result of polymorphisms on antioxidant enzymes. These polymorphisms can be risk in ischemic stroke (IS) risk. IS is a disorder with genetic and environmental factors contributing to overall risk. Although a few studies have been conducted, there have been no reports on catalase (CAT C262T), manganese superoxide dismutase (MnSOD Ala16Val) and glutathione peroxidase 1 (GPX1 Pro198Leu) gene polymorphisms and IS risk. METHODS: We aimed to perform a case-control study to increase the awareness of the impact of oxidative stress (OS) gene polymorphism in the development of IS. A restriction fragment length polymorphism-polymerase chain reaction was used to determine genotypes. The interactions between genes and smoking and possible risk factors were evaluated. RESULTS: An approximately four-fold higher IS risk was found in patients with the Val allele compared to the Ala allele. Smoking was a risk factor in the development of IS for CAT TT and MnSOD Ala/Val genotypes; we found a 3.5- to 5.5-fold higher IS risk in CAT TT and MnSOD Ala/Val genotypes. Different logistic regression models were performed for possible risk factors (smoking, body mass index, low-density lipoprotein and diabetes mellitus). The IS risk increases statistically significant only with age by multiple logistic regression analysis. CAT gene polymorphisms in IS patients were not different from controls. CONCLUSIONS: It is unlikely that CAT and GPX1 single nucleotide polymorphisms are risk factors for IS. The results of the present study show that smoking may be a risk factor for IS risk in patients with MnSOD mutant genotypes.

The impact of detoxifying and repair gene polymorphisms on oxidative stress in ischemic stroke.

Stroke is a multifactorial disease caused by the combination of certain risk factors and genetic factors. There are possible risk factors having important role in the pathogenesis of stroke. The most important environmental factors are cigarette smoking and oxidative stress which have different sources. GST (M1, T1, P1) have major roles in detoxification of the products of oxidative stress and they are polymorphic. DNA damages can also be repaired by repair enzymes such as OGG1 and XRCC1 which are highly polymorphic and have pivotal roles in repair systems. In the present study, we investigated that polymorphisms in genes involved in detoxification and DNA-repair pathways might modify the individual's risk for ischemic stroke. Furthermore, the products of oxidative stress and antioxidant capacity were measured and the impact of gene polymorphism on them was evaluated. Our data showed that OGG1 Ser326Cys and XRCC1 Arg399Gln gene polymorphisms had impacts on the development of stroke.

Are changes in olanzapine-induced liver enzyme levels associated with GSTT1, GSTM1, GSTP1, and OGG1 gene polymorphisms?

Olanzapine treatment sometimes produces transient liver biochemistry abnormalities, and such drug-induced liver injuries are mainly monitored by measuring blood levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), whereas alpha-glutathione-S-transferase (α-GST) is not routinely measured in clinics, even though it can serve as an earlier and more specific biomarker of liver damage. Susceptibility to drug-induced liver injury can much depend on the gene polymorphisms regulating the activity of DNA detoxification and repair enzymes. The aim of this study was to evaluate which of the three liver enzymes - α-GST, ALT, and AST - is the most sensitive biomarker of olanzapine-induced liver injury and how their blood levels are affected by the GSTT1, GSTM1, GSTP1, and OGG1 gene polymorphisms in 30 olanzapine-treated patients. Contrary to our hypothesis, the increase in serum α-GST levels was not significantly greater than that of the transaminases. ALT turned out to be an earlier biomarker of liver injury than the other two enzymes. No significant association was found between gene polymorphisms and liver enzyme levels, save for GSTP1 Ile/Val + Val/Val and ALT, which points to this genotype as a risk factor for drug-induced liver injury. Future studies might help to identify the underlying mechanisms of transient liver enzyme increase associated with this genotype.

COVID-19: Are Experimental Drugs a Cure or Cause?

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a new strain of coronavirus. It is characterized by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It has quickly influenced all over the world since it spreads easily. Common symptoms are fever, cough, difficulty in breathing and muscle aches. Despite the urgent need to find an effective antiviral treatment, already available agents are being used alone or in combination all over the world. At the beginning of the pandemic, death rates of infection caused by COVID-19 are high but "is COVID-19 responsible for all deaths?", or "are there any contributions of the frequently used drugs in this period to these deaths?" Surely herd immunity plays a major role and has contributed to the decline in mortality rates. Meanwhile, it is kept in mind that due to safety concerns, changes have also been made in the dosage and combined use of frequently used drugs. OBJECTIVE: In this review, answers to two questions above and the safety of treatments, toxicities of agents involving chloroquine, hydroxychloroquine, remdesivir, favipiravir, lopiravir/ritonavir, sarilumab, tocilizumab, siltuximab, corticosteroids and bromhexine which are the most frequently used in Turkey and all over the world will be summarized. CONCLUSION: Among these drugs, favipiravir seems the most promising drug due to more tolerable adverse effects. More clinical trials with large sample sizes are needed to find the most effective and safe drug for COVID-19 treatment.

Metabolomics mapping changed after olanzapine therapy in drug-naive schizophrenia patients-the significant impact of gene polymorphisms.

Oxidative stress may contribute to the development of schizophrenia and antipsychotics used in schizophrenia treatment may also cause oxidative stress. Gene polymorphisms on antioxidant and repair enzymes are responsible for individual variations and may change the efficacy of olanzapine treatment among schizophrenia patients. In our study, we assessed oxidative stress-related metabolite changes due to genetic polymorphisms on first diagnosed-schizophrenia patients treated with olanzapine. Blood samples (n = 30 patients) were taken before treatment (T1), after 10 ± 1 days (T2), and after 3 ± 1 months (T3). T1 served as control for T2 and T3, since it is advantageous to perform on same patient to evaluate the impact of olanzapine only. GSTs (GSTM1, GSTT1, and GSTP1) and OGG1 gene polymorphisms were analyzed by polymerase chain reaction. Changes in metabolites were detected with metabolomics profiling by gas chromatography-mass spectrometry according to each genotype before and after treatment. Multivariate analysis showed that metabolomics profiles differed after olanzapine treatment regardless gene polymorphisms. Tryptophan could be a biomarker in response to olanzapine treatment since its levels were increased after treatment. GSTM1 gene polymorphism caused significant changes in some metabolites after treatment. Urea, palmitic acid, and caprylic acid levels increased and alanine levels decreased in patients with GSTM1 null genotypes after olanzapine. In future, targeted metabolomics with these prominent metabolites and assessing gene expressions of GSTs will be beneficial to understand the mechanism of action.

Association of vitamin D receptor polymorphisms with vitamin D and calcium levels in Turkish multiple sclerosis patients.

Aim: The present study was conducted to assess the impact of gene (vitamin D receptor [VDR] polymorphisms) - environment (serum vitamin D and calcium levels) interaction on multiple sclerosis (MS) risk. Materials & methods: FokI, BsmI, TaqI and ApaI genotyping were performed in 149 MS patients and 127 controls. We measured serum vitamin D and calcium levels. Results: No significant difference between VDR polymorphisms and MS risk was detected. In patients with FokI ff, BsmI Bb, TaqI Tt and ApaI AA genotypes, vitamin D levels were statistically higher. Serum calcium levels were significantly lower in patients with FokI FF, Ff, all BsmI and TaqI genotypes and ApaI AA and Aa genotypes. Conclusion: No significant association was found between VDR polymorphisms with MS risk.

Vitamin D deficiency stands out as an important environmental factor in multiple sclerosis (MS). In recent years, the role of genetic factors associated with vitamin D has also been examined. In addition to the effects of smoking habit, exposure to ultraviolet rays, latitude and inflammatory diseases on MS risk, high vitamin D levels are thought to be protective. Therefore, investigation of genetic factors that play a role in vitamin D metabolism will be helpful in elucidating the etiology of MS disease and in the development of treatment options.

Individual susceptibility has a major impact on strong association between oxidative stress, defence systems and Parkinson's disease.

Oxidative stress plays an important role in the degeneration of dopaminergic neurons, which causes Parkinson's disease (PD). Oxidative stress products, antioxidant and their balance have important roles in the development of oxidative stress-based PD. The impact of reactive oxygen species (ROS) and defence systems can be altered by genetic polymorphisms, and thus the risk of PD may also be affected. We aimed to investigate the possible association of individual susceptibility with the development of oxidative stress-based PD. For this purpose, we measured serum levels of folic acid, homocysteine, Vitamin B6 and B12 that play roles in folate-dependent one-carbon pathway, oxidant or antioxidant enzymes (NADPH oxidase, MnSOD, GPX), 8-OHdG and repair enzymes (OGG1, XRCC1 and MTH1) by ELISA, and analysed related gene polymorphisms by PCR-RFLP. XRCC1, ROS, NADPH and folic acid levels were found to be statistically higher in patients than controls. XRCC1, MnSOD and GPX activities were increased. We observed higher levels of 8-OHdG in patients with MnSOD and XRCC1 mutant genotypes and higher XRCC1 levels in patients with NOX p22 fox mutant genotypes rather than controls. We suggest that routinely clinical validation of major oxidative stress-related biomarkers will be a good approach to manage detrimental effects of PD.

Exposure to particulate matter: a brief review with a focus on cardiovascular effects, children, and research conducted in Turkey.

Exposure to environmental particulate matter (PM), outdoor air pollution in particular, has long been associated with adverse health effects. Today, PM has widely been accepted as a systemic toxicant showing adverse effects beyond the lungs. There are numerous studies, from those in vitro to epidemiological ones, suggesting various direct and indirect PM toxicity mechanisms associated with cardiovascular risks, including inflammatory responses, oxidative stress, changes in blood pressure, autonomic regulation of heart rate, suppression of endothelium-dependent vasodilation, thrombogenesis, myocardial infarction, and fibrinolysis. In addition to these and other health risks, considerations about air quality standards should include individual differences, lifestyle, and vulnerable populations such as children. Urban air pollution has been a major environmental issue for Turkey, and this review will also address current situation, research, and measures taken in our country.

Role of gene polymorphisms in vitamin D metabolism and in multiple sclerosis.

Multiple sclerosis (MS) is a complex inflammatory disease of the central nervous system (CNS) resulting in neurological impairment and disability. There is evidence that adequate vitamin D levels may lower the risk of MS development. The aetiology of MS is complex and involves both genetic and environmental factors. In fact, not one but several genes are believed to lead to the disease. As for environmental factors, one of the most important risk factors is vitamin D deficiency, which, in turn, is closely related to gene polymorphisms that play a role in vitamin D metabolism and regulation. However, information about these gene polymorphisms is quite contradictory. The aim of this review is to discuss the association between some of the vitamin D-related gene variants and MS.