L-Carnitine (β-hydroxy-γ-trimethyl aminobutyric acid) plays a critical role in inflammatory diseases by modulating inflammatory cell functions. Inducible nitric oxide synthase (iNOS), a proinflammatory enzyme responsible for the generation of nitric oxide (NO), has been implicated in the pathogenesis of inflammatory diseases. Mechanism of action of L-carnitine on inflammation via iNOS and nuclear factor κB (NF-κB) is unclear. In this study, we aimed to investigate the effect of L-carnitine on nitric oxide synthesis in lipopolysaccharide (LPS)-stimulated RAW 264·7 macrophage cells. For this purpose, cells were pretreated with various concentrations of L-carnitine and subsequently incubated with LPS (1 µg·ml(-1) ). NO levels, iNOS protein expression, and NF-κB activity were determined using colorimetric detection, Western blotting and transfection assays. Our results showed that treatment with L-carnitine suppressed nitric oxide production, iNOS protein expression and NF-κB activity. We demonstrated that inhibitory effect of L-carnitine on iNOS protein expression is at transcriptional level. This study may contribute to understanding the anti-inflammatory effect of L-carnitine.
Glutathione S-transferases (GSTs) are phase II enzymes that detoxify hazardous xenobiotics including carcinogens. Inter-individual variations in GSTM1 and GSTT1 loci have been associated with several types of cancer, including leukemias. In this study, we investigated the possible association between GSTM1 and GSTT1 polymorphisms and susceptibility to chronic myeloid leukemia (CML) in a Turkish population. In a case-control study, 106 CML patients and 190 healthy controls were evaluated for GSTM1 and GSTT1 polymorphisms. GSTM1 null (GSTM1(-)) genotype frequencies in CML cases and controls were 45.3% and 42.6%, respectively. GSTT1 null (GSTT1(-)) genotype frequencies were 44.3% and 18.4%, respectively. The frequency of the GSTT1(-) genotype among CML patients was significantly higher than in controls [odds ratio (OR) 3.53, 95% confidence interval (CI) 2.08-6.00; P < 0.0001]. Individuals with the GSTM1(-) genotype did not have increased risk of CML [OR: 1.11; 95% CI: 0.69-1.80; P = 0.714]. The combined GSTM1(-)/GSTT1(-) genotype was significantly associated with risk of CML compared to the GSTM1(+) /GSTT1(+) genotype which was most frequent in both cases and controls [OR: 9.47; 95% CI: 3.61-24.87]. Similar findings have only been obtained in Turkish and Indian populations but not elsewhere. The GSTM1(+) /GSTT1(-) genotype was associated with a 2.5-fold increased risk compared with the GSTM1(-)/GSTT1(+) genotype, the second most frequent genotype (OR; 2.46; 95% CI: 1.17, 5.20), suggesting a complex interaction between GSTM1 and GSTT1. Our results indicate an association between the GSTT1(-) genotype, either alone or in combination with GSTM1(-) genotype, and risk of CML, suggesting a possible interaction between GSTM1 and GSTT1. These findings, which are possibly restricted to Turkey and India, warrant further research.
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