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Diabetes is a state of increased oxidant stress and there is evidence that oxidation may play a role in the genesis of complications. Gliclazide, a sulfonylurea hypoglycemic drug, has been shown to possess free radical scavenging properties. This study examined the effects of in vitro supplementation with gliclazide and other sulfonylureas as on low-density lipoprotein (LDL) oxidation and the total plasma antioxidant capacity (TPAC). In a separate study, the effects of 10 months of oral gliclazide therapy on oxidative parameters were assessed in 44 type 2 diabetic patients. Gliclazide, but not glibenclamide, glimepiride, glipizide or tolbutamide, inhibited LDL oxidation and enhanced TPAC. With the addition of 1 microM gliclazide, oxidation lag time increased from 53.6+/-2.6 to 113.6+/-5.1 min (p<0.001), and TPAC increased from 1. 09+/-0.11 to 1.23+/-0.11 mM (p<0.01). Administration of either modified release or standard gliclazide to type 2 diabetic patients resulted in a fall in 8-isoprostanes, a marker of lipid oxidation, and an increase in the antioxidant parameters TPAC, SOD and thiols. These studies show that gliclazide possesses antioxidant properties that produce measurable clinical effects at therapeutic doses.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11004429&dopt=Abstract
Biol Res. 1994;27(2):135-43.
Stress-induced hyperglycemia and hypoinsulinemia are suppressed by sulfonylurea. Predominant role of insulin.
Vargas L, Paredes O, Kawada ME.
Departamento de Biologia Celular y Molecular, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago, Chile.
Based on the in vitro blockade of adrenal catecholamines release by sulfonylurea, we searched for an anti-stress activity of this drug. Stress-induced hyperglycemia and insulin inhibition were employed as adrenergic stress indicators. A standard dose of the oral sulfonylurea glipizide (200 micrograms/100 g), administered 15 min before a 1-h restraint stress to intact or 80% pancreatectomized rats, produced total suppression of the stress-induced hyperglycemia-hypoinsulinemia, an effect followed by a significant post-stress hypoglycemia of 1 h duration. The latter effect was elicited by all the sulfonylureas assayed. In the 80% pancreatectomized rats, glipizide nearly halved the increases in plasma catecholamines at 30 min of stress, but did not modify those attained at 60 min, when glycemia was decreasing and insulinemia was still increasing. Moreover, behavioral experiments in intact stressed rats showed that the adrenergic overt behavior inhibition caused by propranolol was not produced either by glipizide or insulin, reinforcing that glipizide affect was not mediated by catecholamine inhibition. These findings suggest a blockade of catecholamines hepatic receptors by the anticipated insulin release induced by sulfonylurea. Thus, insulin fully dominated when insulin and catecholamines were administered in a stress-like sequence. A confirmation of these findings in diabetic patients subjected to surgical stress would allow a new therapeutic application of sulfonylurea. It is concluded that an anticipated insulin release plus an insulin dominant role over catecholamines activity might explain the anti-stress effect of sulfonylurea.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8640242&dopt=Abstract
Anal Chem. 1995 Oct 15;67(20):3668-75.
Detection of hypoglycemic drugs in human urine using micellar electrokinetic chromatography.
Nunez M, Ferguson JE, Machacek D, Jacob G, Oda RP, Lawson GM, Landers JP.
Department of Laboratory Medicine and Pathology, Mayo Foundation/Mayo Clinic, Rochester, Minnesota 55905, USA.
Micellar electrokinetic chromatography (MEKC) is evaluated as a potential analytical method for the separation and detection of a series of sulfonylurea drugs used in the treatment of hyperglycemia. These drugs are often surreptitiously abused, producing extremely low blood glucose levels and symptoms indistinguishable from those associated with an insulin-secreting tumor. Separation buffer containing 50 mM sodium dodecyl sulfate (SDS) was found to be adequate for the MEKC separation of the third generation drugs (glipizide and glyburide) but not the second generation drugs (acetohexamide chlorpropamide, tolazamide, and tolbutamide). At a pH of 8.5 in the presence of 20 mM borate/20 mM phosphate and 150 mM SDS, all seven components were adequately resolved with an analysis time of 17 min. Altering the concentration of the buffering components to either 5 mM borate/5 mM phosphate or 40 mM borate alone reduced the analysis time to less than 10 min with no observable loss in resolution. A series of other micelle-forming surfactants were evaluated, and only sodium cholate provided an improvement over the SDS-based system. Optimal separation was obtained with 75 mM sodium cholate and led to complete analysis with baseline resolution of all seven components in less than 8 min. These conditions were shown to be adequate for the detection of the hypoglycemic drugs spiked into normal urine and in patients taking these drugs. The precision associated with nine consecutive injections of six samples (n = 54) was found to be acceptable with percent coefficient of variance for absolute migration times (MTabs) for all peaks averaging 0.89 with peak area and peak height being 8.49 and 8.26, respectively. The between-sample precision was found to average 0.92% for MTabs and 8.56% and 8.45%, respectively, for the relative peak area and peak height. With a detection limit for the drugs in urine (following extraction) in the 50 ng/mL range, the potential exists for an MEKC-based assay for the detection of sulfonylurea drugs in urine.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8644918&dopt=Abstract
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