Aminoguanidine Treatment In Rats Research Articles

The Effect of Aminoguanidine Treatment, With or Without Food Restriction on the Liver, Stomach and Small Intestine of the Rat

A comparative investigation has been made into the effects of aminoguanidine treatment (60 mg kg-1 day-1) with or without dietary restriction (i.e. 50% reduction in food intake) on the protein, RNA and DNA composition of the liver, small intestine and stomach of young rats (0.1 kg body weight). After 3 weeks of dietary restriction the wet weights of the liver and small intestine decreased by 56 and 52%, respectively. There were significant reductions (approx 50%) in total hepatic and intestinal protein, RNA and DNA. Changes in ratios of RNA/protein, RNA/DNA and protein/DNA were only significant for intestinal RNA/DNA, where a 15% reduction was observed. In contrast, stomach wet weight and total protein content were unaltered by dietary deprivation. Stomach RNA and DNA contents were reduced by only 18-21%, and the protein/DNA ratio increased by 22%. Similar responses of liver, small intestine and stomach to dietary deprivation were observed in aminoguanidine-treated rats. Aminoguanidine-treatment of rats on an unrestricted diet for three weeks had no effect on the wet weights, total protein, RNA or DNA contents of the liver, stomach or small intestine. In dietary-restricted rats, and stomach were unaffected by the treatment. However, aminoguanidine treatment of dietary-restricted rats caused significant increases in the amounts of intestinal protein, RNA and DNA by approximately 15%. The treatment abolished the dietary restriction-induced decrease in total intestinal DNA/body weight. The wet weights of the lung, diaphragm, kidney, spleen and testes of both fed and dietary-restricted rats were also unaffected by aminoguanidine.(ABSTRACT TRUNCATED AT 250 WORDS)

Inducible Nitric Oxide Synthase Expression after Traumatic Brain Injury and Neuroprotection with Aminoguanidine Treatment in Rats

Inducible Nitric Oxide Synthase Expression after Traumatic Brain Injury and Neuroprotection with Aminoguanidine Treatment in Rats

Inducible Nitric Oxide Synthase Expression after Traumatic Brain Injury and Neuroprotection with Aminoguanidine Treatment in Rats

Inducible Nitric Oxide Synthase Expression after Traumatic Brain Injury and Neuroprotection with Aminoguanidine Treatment in Rats

Inducible Nitric Oxide Synthase Expression after Traumatic Brain Injury and Neuroprotection with Aminoguanidine Treatment in Rats

Inducible Nitric Oxide Synthase Expression after Traumatic Brain Injury and Neuroprotection with Aminoguanidine Treatment in Rats

Inducible Nitric Oxide Synthase Expression after Traumatic Brain Injury and Neuroprotection with Aminoguanidine Treatment in Rats

Inducible Nitric Oxide Synthase Expression after Traumatic Brain Injury and Neuroprotection with Aminoguanidine Treatment in Rats

Inducible nitric oxide synthase expression after traumatic brain injury and neuroprotection with aminoguanidine treatment in rats.

We investigated the time course of inducible nitric oxide synthase (iNOS) enzymatic activity and immunocytochemical localization of iNOS expression after traumatic brain injury (TBI), as well as the possible role of iNOS in the pathogenesis of TBI. Male Sprague-Dawley rats were anesthetized and underwent moderate parasagittal fluid-percussion brain injury. Rats were decapitated 5 minutes, 6 hours, 1 day, 3 days, 7 days, or 14 days later, and iNOS enzymatic activities were measured (n = 6-8). To determine whether nitric oxide produced by iNOS contributed to the histopathological consequences of TBI, inhibition of iNOS activity using aminoguanidine (intraperitoneal injections of 100 mg/kg aminoguanidine [n = 9] or vehicle [n = 8], twice each day) was conducted for 3 days. Significantly elevated iNOS activity was detected at 3 days (276.8+/-72.3% of contralateral value, means +/- standard errors; P < 0.05), and the most robust increase occurred 7 days after TBI (608.0+/-127.0%, P < 0.01) in the injured parietal cerebral cortex. Immunostaining for iNOS and glial fibrillary acidic protein, at 3 and 7 days after TBI, revealed that the major cellular sources of iNOS expression were cortical Layer 1 astrocytes and macrophages within the subarachnoid space. Administration of aminoguanidine did not reduce contusion volume significantly; however, treatment reduced total cortical necrotic neuron counts (1367.6+/-210.3; P < 0.01, compared with vehicle, 2808.5+/-325.1). These data indicate that iNOS is expressed after moderate parasagittal fluid-percussion brain injury, in a time-dependent manner, and that inhibition of iNOS synthesis improves histopathological outcomes. Thus, inhibition of iNOS activation may represent a potential therapeutic strategy for the treatment of TBI.