Disease relevance of aminoguanidine

• The identification of aminoguanidine as an inhibitor of advanced nonenzymatic glycosylation product formation now makes possible precise experimental definition of the pathogenetic significance of this process and suggests a potential clinical role for aminoguanidine in the future treatment of chronic diabetic complications [1].
• Aminoguanidine, when administered to mice sensitized to develop experimental autoimmune encephalomyelitis, inhibited disease expression in a dose-related manner [2].
• Histologic scoring of the spinal cords for inflammation, demyelination, and axonal necrosis revealed significantly less pathology in the aminoguanidine-treated group [2].
• Treatment with aminoguanidine, a preferential inhibitor of inducible nitric oxide synthase, was associated with enhanced proliferation of alpha-smooth muscle actin immunoreactive cells and the intensity of obliterative bronchiolitis early after transplantation [3].
• In a model of controlled cortical impact (CCI) with secondary hypoxemia, rats were treated with vehicle or with 1 of 2 iNOS inhibitors (aminoguanidine and L-N-iminoethyl-lysine), administered by Alzet pump for 5 days and 1 [4].

Psychiatry related information on aminoguanidine

• We found that 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine (10 mg/kg, i.p.) or aminoguanidine (400 mg/kg, i.p.) was capable to suppress rapid-eye-movement sleep and induce a delayed enhancement in slow-wave sleep in old rats [5].
• In the mouse heat radiation tail-flick assay, aminoguanidine significantly prolonged the tail-flick latency of animals, suggesting that the pain threshold was elevated [6].
• Also, the development of morphine dependence as assessed by naloxone-precipitated withdrawal manifestations was reduced by co-administration of aminoguanidine [7].
• As aminoguanidine prevents AGE formation, erectile dysfunction in diabetes is probably caused partly by the generation of AGEs [8].
• Pretreatment with aminoguanidine or FK506 improved the behavioral symptoms and survival rate [9].

High impact information on aminoguanidine

• In a group of diabetic patients treated with the advanced glycosylation inhibitor aminoguanidine, Hb-AGE levels decreased significantly over a 1-month period [10].
• Aminoguanidine administration to rats was equally effective in preventing diabetes-induced formation of fluorescent advanced nonenzymatic glycosylation products and cross-linking of arterial wall connective tissue protein in vivo [1].
• Aminoguanidine, a selective inhibitor of the iNOS, inhibited the in vitro production of nitric oxide by cells isolated from individual implantation sites, and more strikingly, significantly reduced early embryo losses in CBA/J females mated by DBA/2 males when given orally or parenterally to the gravid females starting on day 6 of gestation [11].
• Aminoguanidine treatment prolonged graft survival, improved graft contractile function, and significantly reduced the histologic grade of rejection [12].
• In addition, aminoguanidine-treated pregnant mice showed a significant increase in average litter size when the pregnancies were allowed to proceed to term.(ABSTRACT TRUNCATED AT 400 WORDS)[11]

Chemical compound and disease context of aminoguanidine

• Since advanced glycosylation end products have been suggested to mediate hyperglycemia-induced microvascular atherogenesis and because aminoguanidine (AG) prevents their generation, we examined whether AG could prevent or ameliorate the physiologic and biochemical indices of streptozotocin (STZ)-induced experimental diabetic neuropathy [13].
• To evaluate these hypotheses, we examined the effect of captopril, an afterload-reducing agent, and aminoguanidine, a nucleophilic hydrazine that prevents the accumulation of collagen AGEs, on left ventricular end-diastolic (LVED) compliance after 4 months of streptozotocin (0.26 mmol/kg)-induced diabetes mellitus in rats [14].
• In contrast, the addition of aminoguanidine at 10 mM concentration to the culture media protected pericytes from glucose toxicity [15].
• AGE inhibitors such as aminoguanidine and pyridoxamine (PM) have proven effective in animal model and clinical studies as inhibitors of AGE formation and development of diabetic complications [16].
• Treatment with the iNOS inhibitor, aminoguanidine, reduced NO3- levels in serum of C57BL/6 mice and eliminated resistance of these hosts to P. chabaudi AS malaria without affecting parasitemia [17].

Biological context of aminoguanidine

• The arterial pulse pressure in aminoguanidine-treated rats was decreased (-15%, P < 0.05) and the pulsatile component of left ventricular power output was relatively diminished (-35%, P < 0.05) [18].
• These results indicate an increased vascular elasticity, an improved left ventricular-arterial coupling, and a decreased vascular permeability in diabetic rats after aminoguanidine treatment, suggesting that AGE-accumulation on collagen negatively affects arterial wall properties in experimental diabetes [18].
• RESULTS: Kupffer cells reduced proliferation and induced apoptosis of AH70 cells, which were attenuated by the NO synthesis inhibitors NG-monomethyl-L-arginine and aminoguanidine [19].
• Treatment with the selective iNOS inhibitor, aminoguanidine, inhibited iNOS enzymatic activity and overproduction of NO2-/NO3-. LPS-induced bacterial translocation was reduced by aminoguanidine [20].
• These data indicate that aminoguanidine inhibits oxidative modification of LDL protein in large part by binding reactive aldehydes formed during lipid peroxidation and preventing their subsequent conjugation to apo B [21].

Anatomical context of aminoguanidine

• Aminoguanidine treatment did not affect iNOS mRNA synthesis or intragraft nitric oxide production, but decreased iNOS immunoreactivity in smooth muscle cells [3].
• RESULTS: Fluid secretion in inflamed gallbladders was reversed to a net absorption in response to the NO synthase blockers N omega-nitro-L-arginine and aminoguanidine, and formation of nitrate was reduced [22].
• To test this hypothesis we oxidized LDL by incubation with Cu2+ or with endothelial cells in the absence or presence of aminoguanidine [21].
• In contrast, after the same time in culture but in medium supplemented with aminoguanidine, which inhibits serum amine oxidase, crisis occurred in only 1 of 41 cell lines [23].
• In contrast, aminoguanidine-treated diabetic animals had only a 3.6-fold increase in acellular capillaries and no microaneurysms [24].

Associations of aminoguanidine with other chemical compounds

• In cultured prediabetic ZDF islets, FFA induced a fourfold greater rise in NO, upregulated mRNA of inducible nitric oxide synthase (iNOS), and reduced insulin output; both nicotinamide and aminoguanidine, which lower NO, prevented the FFA-mediated increase in iNOS mRNA, reduced NO, and minimized the loss of insulin secretion [25].
• Ileal mucosal homogenates from the resection group receiving aminoguanidine, when compared with those from resection controls, showed no diamine oxidase activity with increased putrescine content and ornithine decarboxylase activity [26].
• Alternatively, administration of aminoguanidine (7.35 mmol x kg(-1) x d(-1)) prevented both the enhanced myocardial collagen fluorescence (7.1+/-1.2) and the increased slope of the linearized LVED stress-LVED strain relation (29+/-2) but did not change markers of blood glucose control [14].
• Nitric oxide production in islets from nonobese diabetic mice: aminoguanidine-sensitive and -resistant stages in the immunological diabetic process [27].
• Presumably this occurs because early glycosylation products preferentially bind to aminoguanidine rather than to lysine groups of adjacent proteins [21].

Gene context of aminoguanidine

• The iNOS inhibitor aminoguanidine markedly enhances in vitro resorption by activated NOS-rich chick osteoclasts and by normal rat osteoclasts treated with LPS or IFN-gamma [28].
• To further characterize these responses and determine if they are related, recipient BALB/c H-2d mice were treated with aminoguanidine (AMG), a selective inhibitor of inducible nitric oxide synthase (iNOS), and transfused weekly with 2 x 10(8) C57BL/6 H2b platelets [29].
• Inhibition of NO production in LPS-treated macrophages by either the L-arginine analogue N(G)-monomethyl-L-arginine (L-NMMA) or aminoguanidine was accompanied by an additional enhancement of Cox activity parallel to the expression of Cox-2 protein analyzed by Western blot [30].
• Nevertheless, the underlying importance of NO is illustrated by the finding that aminoguanidine treatment leads to more severe liver disease and reduced time to death in infected IL-4-/- mice [31].
• NO- and caspase 1 seem to be independently activated in that aminoguanidine did not affect caspase 1 activation and the inhibitor of caspase 1, Tyr-Val-Ala-Asp-acylooxymethylketone, did not block NO- production; however, both treatments inhibited apoptosis [32].

Analytical, diagnostic and therapeutic context of aminoguanidine

• Aminoguanidine treatment increases elasticity and decreases fluid filtration of large arteries from diabetic rats [18].
• Normotensive WAG/Rij rats were treated from 24 to 30 mo with aminoguanidine and compared with a control group [33].
• Aminoguanidine did not affect the mild histological changes of rejection present in allografts [34].
• Conversely, the resistance-inducing effect of the fibroblasts was significantly abolished, when the specific iNOS inhibitor aminoguanidine was added during coculture [35].
• AGE inhibitors such as aminoguanidine and pyridoxamine (PM) inhibit both the formation of AGEs and development of complications in animal models of diabetes [36].

References