Genotype and allele frequencies of N-acetyltransferase 2 and glutathione S-transferase in the Iranian population

1. Xenobiotic-metabolizing enzymes constitute an important line of defence against a variety of carcinogens. Many are polymorphic, constituting the basis for the wide interindividual variation in metabolic capacity and possibly a source of variation in the susceptibility to chemical-induced carcinogenesis. The aim of the present study was to determine the frequencies of important allelic variants in the N-acetyltransferase 2 (NAT2) and glutathione S-transferase (GST) genes in the Iranian population and compare them with frequencies in other ethnic populations. 2. Genotyping was performed in a total of 229 unrelated healthy subjects (119 men, 110 women) for NAT2 and 170 unrelated healthy subjects (89 men, 81 women) for GST from the general Tehran population. A combination of polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) was applied for typing of NAT2 polymorphisms. Detection of GSTM1 and GSTT1 null alleles was performed simultaneously using a multiplex PCR assay. 3. The frequencies of specific NAT2 alleles were 0.299, 0.314, 0.380, 0.007 and 0.000 for *4 (wild-type), *5 (C481T, M1), *6 (G590A, M2), *7 (G857A, M3) and *14 (G191A, M4), respectively. The most prevalent genotypes were NAT2 *5/*6 (29.70) and *4/*6 (21.40). The GSTM1- and GSTT1-null alleles were detected in 44.7 and 21.2 of subjects, respectively. 4. We found that Iranians resemble Indians with regard to allelic frequencies of the tested variants of NAT2. The predominance of slow (49.36) and intermediate (41.47) acetylation status compared with wild-type rapid acetylation status (9.17) in the study group suggests the significant prevalence of the slow acetylator (SA) phenotypes in the Iranian population. Our data confirmed that Iranians are similar to other Caucasian populations in the frequency of both GSTM1- and GSTT1-null alleles. © 2007 The Authors

Influence of citicoline on citalopram-induced antidepressant activity in depressive-like symptoms in male mice

Depression is associated with significant functional disabilities. Application of new drugs which could enhance the effectiveness of antidepressants drug and reduce side effects of their long-term use seems necessary. Citicoline is used as an effective chemical agent for improving the symptoms of some neurodegenerative diseases. Therefore, in this survey, the application of citicoline as an adjuvant drug was evaluated in mice model of depression. A total of 180 adult NMRI male albino mice were used in this study. All groups were exposed to chronic unexpected mild stress (CUMS) followed by treatment with various doses of citalopram or/and citicoline or saline for 21 days. Sucrose preference (SP), open field (OF), and forced swimming test (FST) were applied to evaluate depression symptoms in the groups. The results indicated that only citicoline at the 5 mg/kg dose had shifted its status from being noneffective to become significantly effective in the co-administered group. The means of SP, OFT, and FST of the treatment groups were significantly different in favor of co-administered group compared with the other groups as well as the control group. Based on the results, it can be concluded that administration of citicoline, as an adjuvant drug, in combination with citalopram, enhanced the effectiveness of selective serotonin reuptake inhibitors (SSRI) drugs for depression treatment. © 201