Paraoxonase-1 activity, malondialdehyde and glutathione peroxidase in non-alcoholic fatty liver disease and the effect of atorvastatin

The prevalence of non-alcoholic fatty liver disease [NAFLD] appears to be increasing. The aim of the present study was to investigate the relationship between hepatic antioxidant paraoxonase 1 [PON1] activity, lipid peroxidation and antioxidant enzymes in patients with NAFLD and the effect of atorvastatin. This study was conducted on 50 patients with NAFLD and 20 normal subjects matched for age and sex. All of them were subjected to the following investigations: abdominal ultraso-nography, serum PON1 activity level, liver function tests, serum lipid profile, fasting and postprandial blood glucose and serum levels of malondialdehyde [MDA] and glutathione peroxidase [GP]. NAFLD patients were further randomly classified into two groups [25 patients each], groups Ia and Ib. Only group la received atorvastatin 40 mg tablet for 8 months. Obesity, dyslipidaemia and impaired glucose tolerance were prevalent in group I. There was a significant decrease in serum PON1 activity with a significant increase in MDA and GP activity [i.e., there is a significant increase in lipid peroxidation rate] in group I compared with group II. After atorvastatin therapy, there was a significant increase in serum PNO1 activity and significant decrease in serum MDA levels. Patients with NAFLD show enhanced oxidative stress which may lead to non-alcoholic steatohepatitis [NASH]. Reduced PON1 activity and increased MDA could be considered a biochemical marker for lipid peroxidation, which require follow-up in patients with NAFLD. Atorvastatin may have a role in prevention of, or delay, the transformation of liver steatosis into NASH

Glutathione S-transferase gene T1 and ml polymorphism in type 2 diabetic patients with end-stage renal disease

Diabetes mellitus [DM] is associated with an increased production of reactive oxygen species [ROS] which may contribute to the development of diabetic nephropathy. Therefore, the levels of endogenous antioxidants may be one of determinants of the susceptibility to diabetic nephropathy. Glutathione S-transferases [GSTs] are enzymes involved in the metabolism of many disease-causing electrophilic substrates and protect the cells against oxidative stress. Genetic polymorphisms of the genes coding for enzymes result in different phenotypes with respect to their ability to detoxify these agents. The present study was conducted to determine whether GSTM1 and GSTTl gene polymorphism influences the development of diabetic nephropathy in type 2 DM. The study population consisted of 80 subjects divided into 30 patients type 2 DM with diabetic related end-stage renal diseases [ESRD], 30 patients type 2 DM without nephropathy and 20 subjects apparently healthy individuals as a controls. Multiplex polymerase chain reaction [PCR] was used to analyze GSTM1 and GSTTl polymorphism. GSTTl and GSTM1 gene polymorphism occur more in diabetic patients with ESRD than diabetic patients without nephropathy [GSTM1 null genotype was present in 63% while GSTTl null genotype was present in 60% in group I]. Frequency of homozygous deletion of both GSTTl, GSTM1 was higher in diabetic patients with ESRD [53%] than patients without ESRD [10%], or control [5%], [p<0.05]. Significant negative correlation was found between presence of/GSTMl, GSTTl and albuminuria, serum creatinin and blood urea in diabetic patients with ESRD with a positive correlation between presence of gene GSTTl and GSTM1 null genotype and creatinine clearance where creatinine clearance was lower in patients with GSTT1and GSTM2 deletion, GSTM1 and GSTTl null genotype may play a significant role in the aetiopathogeneses and development of diabetic ESRD and may be a useful marker in the prediction of diabetic ESRD. Also, it can drive approch of genetic therapy in prevention of diabetic nephropathy

Ghrelin, leptin, insulin and insulin resistance in newly diagnosed type 2 diabetic patients

Objectives: To evaluate the hormonal changes ghrelin, leptin, insulin and insulin resistance in newly diagnosed type 2 diabetic patients and their relation to metabolic state

Methods: The present study was carried out on twenty newly diagnosed type 2 diabetic patients and fifteen apparently healthy persons as a control. Fasting plasma insulin, leptin, and ghrelin were measured by ELISA. Homeostasis Model Assessment [HOMA] is an arithmetic way of deriving indices of pancreatic endocrine function [beta cell function, HOMA-B] and peripheral tissue insulin sensitivity [HOMA-S] were calculated from fasting plasma samples

Results: In diabetic group BMI and waist circumference were significantly increase [p<0.0001and p=0.026]. Insulin and leptin were significantly increase [p<0.0001] while, ghrelin was significantly decrease [p<0.0001]. HOMA-S, significantly decrease [p=0.0110] while, HOMA-B non significantly increase. There was a negative correlation between plasma ghrelin and BMI [p=0.0149], waist circumference [p=0.0002], SBP and DBP [p<0.0001] while leptin showed significantly positive correlated with BMI and waist circumference [p<0.0001]. There was a negative correlation between plasma ghrelin and FBS [p=0.0005], PPBS [p<0.0001], and HOMA-B [p=0.0336] with positive correlation with HOMA-S [p<0.0001], while leptin showed significant positive correlation with HOMA-B [p=0.0023] and significant negative correlation with HOMA-S [p<0.0001]. There was a significant negative correlation between plasma ghrelin and serum triglyceride [p<0.001] and LDL cholesterol [p<0.0001] with a positive correlation with HDL cholesterol [p<0.0001] while leptin showed significant positive correlation with serum triglyceride [p=0.0020] and LDL cholesterol [p<0.0001] and significant negative correlation with HDL cholesterol [p<0.0001]. There was a negative correlation between plasma ghrelin and insulin and leptin [p<0.0001] with a positive correlation between insulin and leptin [p< 0.0001]

Conclusion: It is suggested that there is interaction between insulin and leptin hormones. Insulin has stimulatory trophic effect on leptin secretion, but the effect of leptin on insulin is controversial as leptin lowers insulin secretion and in the same time modulates insulin action and participates in the development of insulin resistance. It is speculated also that both insulin and leptin have inhibitory role on ghrelin level. Decreased plasma levels of ghrelin are significantly associated with abdominal adiposity, hyperinsulinemia and insulin resistance in type 2 diabetic patients. These hormonal changes are associated with clusters of metabolic abnormalities which are major CHD risk factors