Clinical pharmacokinetic and pharmacodynamic studies involving thiopentone and propofol

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Genotoxic impact of long-term cigarette and waterpipe smoking on DNA damage and oxidative stress in healthy subjects

Although a plethora of studies have examined tobacco smoke-cancer disease association, the involvement of cellular genetic toxicity remains unclear. Therefore, the present study provides molecular evidence for a pathway involved in the DNA damage induced by long-term cigarette and waterpipe smoke in human subjects. The study population consisted of 45 subjects who were divided into three groups; healthy nonsmokers group, cigarette smokers group, and waterpipe smokers group. A questionnaire and consent form was distributed and signed by all participants. Total RNA was extracted from the blood using PAXgene Blood RNA Kit and mRNA expression levels of target genes were quantified by RT-PCR. Our results showed that 80% of the participants smoke 20-39 cigarettes/day, whereas 12% smoke more than 40 cigarettes/day. With regard to waterpipe smoke, the majority (46%) smoke more than 5 times/week. Both cigarette and waterpipe smokers showed increased the plasma levels 8-hydroxy-2'-deoxyguanosine (8-OHdG), of DNA damage marker. In addition, the mRNA expression levels of DNA repair genes (OGG1 and XRCC1) were significantly inhibited in both cigarette and waterpipe smokers groups by 30% and 60%, respectively. This was associated with a marked decrease (50%) in the expression of detoxifying genes (NQO1 and GSTA1) with an increase in CYP1A1 mRNA expression, a cancer-activating gene. Both cigarette and waterpipe smokers increased in the plasma concentrations of several toxic heavy metals such as Cd (130%), Pb (47%), and Ni (30%). In conclusion: the present findings clearly explore the genotoxic effect of cigarette and waterpipe smoking on human DNA.The present study demonstrates the first evidence of the genotoxic effect of cigarette and waterpipe smoke in humans. This is supported by the following findings: First, induction of oxidative DNA damage marker (8-OHdG) and inhibition of DNA repair genes (OGG1 and XRCC1) by both cigarette and waterpipe smoke at the mRNA and activity levels. Second, inhibition of cytoprotective and antioxidant genes (NQO1 and GST). Third, induction of cancer-activating gene (CYP1A1).Scopu