Endotoxemia results in both the down-regulation of multiple cytochrome P450 genes and the induction of inducible nitric oxide synthase (NOS2). The nitric oxide (NO) released during inflammation has been implicated as the mediator of the decreased catalytic activity and expression of several cytochrome P450 isozymes. We examined the role of NO in the decreases of both gene expression and activit...

We hypothesized that nitric oxide generated by inducible nitric oxide synthase (iNOS) may contribute to the homeostatic role of this agent in hyperthyroidism and may, therefore, participate in long-term control of blood pressure (BP). The effects of chronic iNOS inhibition by oral aminoguanidine (AG) administration on BP and morphological and renal variables in hyperthyroid rats were analyzed. ...

We studied the effects of administration of beta-resorcylidene aminoguanidine (RAG) to Wistar strain rats with experimental diabetes mellitus (DM) induced by streptozotocin. The effects studied included antioxidant levels in plasma and the liver, oxidative damage of lipids represented by the formation of substances reacting with thiobarbituric acid (TBARP) and selected biochemical indicators. T...

Spergualin (SG) and 15-deoxyspergualin (DSG) were more slowly incorporated into L5178Y cells than spermidine. SG and DSG inhibited carrier-mediated transport of [3H]spermidine competitively with inhibition constants of 0.67 mM and 0.45 mM, respectively. Addition of calf serum stimulated uptake of [3H]spermidine into the cells in a serum concentration-dependent manner. The effect was not observe...

The molecular mechanisms underlying endotoxin-induced insulin resistance remain unclear. Endotoxin or lipopolysaccharide (LPS) injection is a potent stimulator of inducible nitric oxide synthase (iNOS). This study in rats, using the specific iNOS inhibitor aminoguanidine, investigated the role of iNOS in endotoxin-induced hyperglycemia and insulin resistance. LPS injection led to hyperglycemia,...

Aging is associated with cardiac hypertrophy and arterial stiffening possibly associated with accumulation of advanced glycation end products (AGEs). We evaluated the effect of aminoguanidine, an inhibitor of AGE production, on end-stage alterations of renal and cardiovascular systems. Normotensive WAG/Rij rats were treated from 24 to 30 mo with aminoguanidine and compared with a control group....

We tested whether endotoxin (lipopolysaccharide, LPS) inhibits IGF-I gene expression in hepatocytes and the possible role of Kupffer cells and nitric oxide (NO) in this effect. LPS decreased IGF-I mRNA in hepatocyte cultures and increased the nitrite + nitrate levels in the culture medium. Furthermore, there was a negative correlation between the IGF-I mRNA and the nitrite+nitrate levels. When ...

Complete inhibition of polyamine catabolism is possible by combined administration of two compounds. Aminoguanidine (25 mg/kg body wt., intraperitoneally) inhibits all reactions that are catalysed by copper-containing amine oxidases (CuAO). The products of the CuAO-catalysed reactions cannot be reconverted into polyamines (terminal catabolism) and therefore usually escape observation. N1-Methyl...

1. Histamine catabolism in vivo was studied in mice subjected to various forms of pretreatment; tissues from mice killed 2.5 min after intravenous injection of (14)C-histamine were assayed for (14)C-histamine, (14)C-methylhistamine and total (14)C.2. Pretreatment of mice with aminoguanidine, an inhibitor of diamine oxidase, strongly increased levels of (14)C-histamine in intestine; pretreatment...

P-glycoprotein (P-gp), one of the important drug-efflux pumps, is known to affect pharmacokinetics and pharmacodynamics of P-gp substrate drugs. We have previously reported that intestinal P-gp expression levels are transiently decreased in streptozotocin (STZ)-induced type 1 diabetic mouse model. Herein, we examined the analgesic effects of orally administered morphine and its pharmacokinetic ...