title: Diazepam and propofol used as anesthetics during open-heart surgery do not cause chromosomal aberrations in peripheral blood lymphocytes.
abstract: Diazepam is a benzodiazepine with anticonvulsant, anxiolytic, sedative and muscle-relaxing properties. Many aspects of its toxicity have been investigated, including genotoxic and carcinogenic effects in various model systems. However, it is still unclear whether diazepam is in fact a genotoxic agent. Propofol is a rapid-onset, short-acting intravenous anesthetic agent. It is used widely for the induction and maintenance of anesthesia as well as for long-term sedation in intensive care units. There is limited information in the literature on its genotoxic effects. Both drugs are commonly used as anesthetic in patients undergoing open-heart surgery. Therefore, we investigated the possible genotoxic effects of propofol and diazepam in those patients, using a chromosomal aberration (CA) assay. Peripheral blood samples were collected from 45 patients before induction of anesthesia and at the end of the anesthesia with diazepam or propofol. In Group I (n=24), anesthesia was induced with 0.2 mg kg(-1) diazepam and 10 microg kg(-1) fentanyl. In Group II (n=21), anesthesia was induced with 1 mg kg(-1) propofol and 10 microg kg(-1) fentanyl. Pancuronium bromide (0.1 mg kg(-1)) was administered for skeletal muscle relaxation in both groups. Anesthesia was maintained by diazepam administration at 5 mg kg(-1) in Group I or by continuous propofol administration at 2-4 mg (kg h)(-1) in Group II. All patients received 0.02 mg kg(-1) pancuronium and 5 microg kg(-1) fentanyl boluses at 30-40 min intervals for anesthesia maintenance. Body temperature was controlled during bypass in the two groups. We found that the mean frequency of CAs in both groups before and at the end of the anesthesia were not statistically significantly different. Our analysis also indicated that age, smoking habit and gender were not confounding factors. In conclusion, our results indicate that diazepam and propofol do not exert genotoxic effects in blood cells during open-heart surgery.
authors.affiliation: Gazi University, Faculty of Pharmacy, Toxicology Department, Hipodrom, Ankara 06330, Turkey. bensu@gazi.edu.tr
authors.forename: B
authors.initials: B
authors.lastname: Karahalil
authors.forename: S
authors.initials: S
authors.lastname: Yağar
authors.forename: G
authors.initials: G
authors.lastname: Bahadir
authors.forename: P
authors.initials: P
authors.lastname: Durak
authors.forename: S
authors.initials: S
authors.lastname: Sardaş
mesh_terms: D000328:Adult; D000368:Aged; D018686:Anesthetics, Intravenous / Q000009:adverse effects; D006348:Cardiac Surgical Procedures; D002869:Chromosome Aberrations / Q000139:chemically induced*; D002877:Chromosomes, Human / Q000187:drug effects; D003975:Diazepam / Q000009:adverse effects* / Q000494:pharmacology; D005260:Female; D005283:Fentanyl; D006801:Humans; D006993:Hypnotics and Sedatives / Q000009:adverse effects; D008214:Lymphocytes / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D015742:Propofol / Q000009:adverse effects*; D012907:Smoking
chemical_list: D018686:Anesthetics, Intravenous; D006993:Hypnotics and Sedatives; D003975:Diazepam; D005283:Fentanyl; D015742:Propofol