Glutathione S-transferase gene polymorphisms in Turkish patients with diabetes mellitus.

Glutathione S-transferases (GSTs) are enzymes involved in the metabolism of many disease-causing electrophilic substrates and protect the cells against oxidative stress. In the present study, we investigated the GSTM1, GSTT1 and GSTP1 gene polymorphisms in diabetic patients and healthy individuals and searched whether polymorphisms in GST genes are associated with diabetes mellitus (DM) in the Turkish population. The study population consisted of 98 unrelated healthy individuals and 98 patients with DM. Genotyping of GSTM1, GSTT1 and GSTP1 genes was performed using real time polymerase chain reaction with a Light Cycler instrument. Patients had a higher frequency of the GSTM1 null genotype than the control group (Odds ratios, OR = 3.7; 95% confidence intervals, CI = 2.05-6.70). However, there was no significant difference in the frequencies of the GSTT1 and GSTP1 gene polymorphisms between the patients and control group. The combined analysis of these three GST genotypes showed a further DM risk increase (OR = 5.7, 95% CI = 1.51-31.07). This is the first study to determine the association of diabetes with GST gene polymorphism in the Turkish population. These results show that GSTM1 null genotype may play a significant role in the aetiopathogeneses of DM and the GSTM1 gene may be a useful marker in the prediction of DM susceptibility of the Turkish population.

Low-exposure cadmium is more toxic on osteoporotic rat femoral bone: mechanical, biochemical, and histopathological evaluation.

This study aimed to investigate the effects of low-exposure Cd on normal and osteoporotic bone. For this purpose, 12-week-old Sprague-Dawley female rats were assigned randomly to a control group, a Cd group, and an ovariectomy (OVX)+Cd group. OVX+Cd rats underwent bilateral ovariectomy via ventral incision. Twelve weeks after ovariectomy, cadmium chloride (CdCl(2)) was given to rats (Cd and OVX+Cd groups) as intraperitoneal (ip) injection of 0.5mg/kg three times a week for 18 weeks and distilled water was given to control group via ip route for 18 weeks. Bone mineral density (BMD) was measured at mid-diaphysis femoral region by dual-energy X-ray absorbsiometry. Cross-sectional area of the femoral shaft was evaluated by computerized tomography. Biomechanical measurements were performed at the mid-diaphysis of the left femur. Collagen fibers were evaluated at light microscopic level. BMD, cortical thickness, cortical area, and femur length were not changed in Cd and OVX+Cd groups in comparision to controls. In the OVX+Cd group, strength, displacement, energy, stress, strain, and toughness were significantly lower than those of the control group. The Cd concentration of bone was significantly increased in the OVX+Cd group compared to that in the control group. Collagen fiber intensity was decreased in all groups except control group. The results of the present study indicate that the administration of low-dose Cd does not affect normal bone biomechanical parameters, but it has a significant effect on osteoporotic bone.

N-acetyltransferase 2 polymorphism in patients with diabetes mellitus.

The arylamine N-acetyltransferases (NATs) are a unique family of enzymes that catalyse the transfer of an acetyl group from acetyl-CoA to the terminal nitrogen of hydrazine and arylamine drugs and carcinogens. Human arylamine NATs are known to exist as two isoenzymes, NAT1 and NAT2. The objective of this study was to identify whether the genetic polymorphism of NAT2 plays a role in susceptibility to Diabetes Mellitus (DM). Ninety-seven patients with DM and 104 healthy controls were enrolled in the study. NAT2*5A, NAT2*6A, NAT2*7A/B and NAT2*14A polymorphisms were detected by using real time PCR with LightCycler (Roche Diagnostics GmbH, Mannheim, Germany). According to our data, the NAT2*5A and NAT2*6A mutant genotypes and NAT2*14A heterozygous genotype were associated with an increased risk of development of DM (OR = 47.06; 95%CI: 10.55-209.77 for NAT 2*5A, OR = 18.48; 95%CI: 3.83-89.11 for NAT2*6A and OR = 18.22; 95%CI: 6.29-52.76 for NAT2*14A). However, the NAT2*7A/B gene polymorphism carried no increased risk for developing DM disease. After grouping according to phenotypes as either slow or fast acetylators, NAT2*6A slow acetylator was found to be a significant risk factor for DM (OR = 6.09; 95%CI: 1.99-18.6, p = 0.02). The results indicate that NAT2 slow acetylator genotypes may be an important genetic determinant for DM in the Turkish population.

Acute effect of single-dose cadmium treatment on lipid peroxidation and antioxidant enzymes in ovariectomized rats.

We investigated the acute effect of single-dose cadmium (Cd) treatment on lipid peroxidation and antioxidant enzymes in liver and kidney of rats following an ovariectomy operation. Twenty-eight female Wistar albino rats were used and were divided into four groups: I, control (n=7); II, cadmium (Cd, n=7); III, ovariectomized (Ovx, n=7); and IV, ovariectomized+cadmium (Ovx-Cd, n=7). Fourteen of the rats were ovariectomized. Twelve weeks later, cadmium chloride (CdCl(2), 5 mg/kg) was administered i.p. as a single dose to the Cd and Ovx-Cd groups. Twenty-four hours after the injection, all rats were sacrificed and had their liver and kidney tissues removed for the measurement of superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) levels. SOD activity showed a significant decrease (P<0.001) in both organs of Ovx and Cd rats in comparison to controls. CAT activity was significantly decreased (P<0.01) in the liver of Ovx and Cd groups but not in the kidneys of both groups compared to control values. MDA concentrations were higher (P<0.05) in both organs of Ovx and Cd rats than those values observed in the control group. Similar patterns of changes were observed in the Ovx-Cd rats, but the increase in the MDA levels and the decrease in the antioxidant enzymes for the Ovx-Cd group were higher than those of the Ovx and Cd groups. Based on the data, it can be stated that cadmium increases the effect of ovariectomy on lipid peroxidation, impairs the antioxidant defense system, and induces oxidative stress.