Effect of Lipoic Acid on Serum Paraoxonase-1 and Paraoxonase-3 Protein Levels and Activities in Diabetic Rats.

The aim of the present study was to investigate the effect of streptozotocin-induced diabetes mellitus and lipoic acid treatment on serum paraoxonase-1 and paraoxonase-3 protein levels and paraoxonase, arylesterase and lactonase activities.36 rats were equally and randomly divided into 4 groups as control, lipoic acid, diabetes and diabetes+lipoic acid. To induce diabetes, a single dose of streptozotocin (40 mg/kg) was injected intraperitoneally to diabetes and diabetes+lipoic acid groups. Lipoic acid (10 mg/kg/day) was injected intraperitoneally for 14 days to lipoic acid and diabetes+lipoic acid groups. Serum PON1 and PON3 protein levels were measured by western blotting. Serum paraoxonase, arylesterase and lactonase activities were determined by the measuring initial rate of substrate (paraoxon, phenylacetate and dihydrocoumarin) hydrolysis.Streptozotocin-induced diabetes mellitus caused a significant decrease whereas lipoic acid treatment caused a significant increase in serum PON1 and PON3 protein levels and paraoxonase, arylesterase and lactonase activities. The increase percent of serum PON3 protein was higher than that of serum PON1 protein and the increase percent of serum lactonase activity was higher than that of serum paraoxonase and arylesterase activities in diabetes+lipoic acid group.We can report that, like PON1 protein, PON3 protein and actually its lactonase activity may also have a role as an antioxidant in diabetes mellitus and lipoic acid treatment may be useful for the prevention of the atherosclerotic complications of diabetes by increasing serum PON1 and PON3 protein levels and serum enzyme activities.

Significance of arginase and ornithine in malignant tumors of the human skin.

During neoplastic development, several aspects of the regulation of polyamine synthesis undergo profound changes. In extrahepatic mammalian tissues in which the urea cycle is not functioning, arginase is believed to supply the cell with ornithine, a non-protein amino acid that is a precursor for biosynthesis of polyamines. Because the activity of ornithine decarboxylase and polyamine levels have been shown to be elevated during carcinogenesis, we decided to investigate the role of arginase in the development of malignant tumors of the human skin and to examine whether arginase activity and ornithine level can be used as biologic markers for distinguishing patients with squamous cell cancer from patients with basal cell cancer. For this purpose, we studied tissue arginase activity and ornithine level in tumor and adjacent normal tissues in 16 patients (55 +/- 10 years of age) with malignant skin tumors (8 of which were squamous cell cancers and 8 of which were basal cell cancers). The mean arginase activity and ornithine levels in tumor tissues (total) were 17.75 +/- 8.54 U/mg protein and 40.89 +/- 14.88 nmol/mg protein, respectively, versus 3.69 +/- 1.71 U/mg protein and 12.98 +/- 6.21 nmol/mg protein, respectively, for normal tissues. The mean specific arginase activity levels in squamous cell and basal cell cancers of the human skin were 18.49 +/- 10.47 U/mg protein and 16.63 +/- 6.00 U/mg protein, respectively. The mean ornithine levels in squamous cell and basal cell cancers of the human skin were 42.45 +/- 19.10 nmol/mg protein and 39.33 +/- 10.19 nmol/mg protein, respectively. Our results indicated that (1) arginase activity and ornithine levels are elevated in squamous cell and basal cell cancers of the human skin; (2) the increased activity of arginase and hence the elevated levels of ornithine may be important in the development of malignant tumors of the human skin; and (3) although arginase activity and ornithine level may be useful for distinguishing patients with malignant skin tumors from healthy subjects, they cannot be used as biologic markers for distinguishing patients with squamous cell cancer from patients with basal cell cancer.

Serum total and lipid-bound sialic acid levels following acute myocardial infarction.

Although serum total sialic acid has been shown to be a cardiovascular risk factor, with elevated levels associated with increased cardiovascular mortality and also with cerebrovascular disease, the reason for the elevation in serum sialic acid content remains obscure. It has been shown that an increased output of serum proteins by the liver due to some type of acute phase reaction may be one of the possible sources of an increased serum sialic acid concentration in patients with myocardial infarction. An increase in the activity of sialidase, which cleaves the terminal sialic acid residues from oligosaccharides, glycoproteins and gangliosides, may also play an important role in the elevation of serum total sialic acid in myocardial infarction. Elevated serum total sialic acid in the blood might result either from the shedding or secreting of sialic acid from the cell membrane surface, or releasing of cellular sialic acid from the cell into the bloodstream due to cell damage after myocardial infarction. The purpose of the present study is to investigate serum total and lipid-bound sialic acid and the enzymes serum lactate dehydrogenase, creatine kinase and aspartate aminotransferase in patients with acute myocardial infarction, at 24 h post-infarction (day 1), 48 h post-infarction (day 2) and 72 h post-infarction (day 3). A possible role of cell damage in the elevation of serum total and lipid-bound sialic acid levels in these patients was also evaluated. In this study, 40 patients with myocardial infarction ranging in age from 42 to 68 years, and 26 healthy volunteers ranging in age from 45 to 71 years were included. Serum total sialic acid determination was carried out by the thiobarbituric acid method of Warren and lipid-bound sialic acfd by the method of Katopodis. Our data shows that a) there is a gradual increase in the levels of serum total sialic acid and lipid-bound sialic acid during the first three days after the acute myocardial infarction and b) the elevation in serum total sialic acid levels correlates with the elevation in lactate dehydrogenase activity only on day 1 following infarction. Therefore, either the shedding or secreting of sialic acid from the cell or cell membrane surface may be partly responsible for an increased serum sialic acid concentration especially on day 1 following myocardial infarction.