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Bo-yi Qin – One of the best experts on this subject based on the ideXlab platform.

  • Modulation by alpha-difluoromethyl-ornithine and Aminoguanidine of pain threshold, morphine analgesia and tolerance.
    European journal of pharmacology, 2003
    Co-Authors: Bo-yi Qin
    Abstract:

    The effects of alpha-difluoromethyl-ornithine (DFMO) and Aminoguanidine, which might influence the metabolism of endogenous agmatine, on pain threshold, morphine analgesia and tolerance were investigated in mice. In the mouse acetic acid writhing test, intracerebroventricular (i.c.v.) injection of DFMO or Aminoguanidine significantly elevated the pain threshold as indicated by a decrease in the number of writhings. DFMO or Aminoguanidine obviously increased the analgesic effect of morphine in the mouse acetic acid writhing test and the mouse heat radiation tail-flick assay. These effects of DFMO and Aminoguanidine were antagonized by idazoxan (3 mg/kg, i.p.), which is a selective antagonist of the imidazoline receptor. In the mouse heat radiation tail-flick assay, Aminoguanidine significantly prolonged the tail-flick latency of animals, suggesting that the pain threshold was elevated. Furthermore, both DFMO and Aminoguanidine enhanced morphine analgesia and inhibited acute morphine tolerance in the mouse heat radiation tail-flick assay. Neither DFMO nor Aminoguanidine inhibited the activity of nitric oxide synthase in different brain areas in mice in vivo. These results indicate that the substances involved in the metabolism of endogenous agmatine could modulate the pain threshold, morphine analgesia and tolerance, indicating the possible role of endogenous agmatine in the pharmacological effects of morphine.

  • Modulation by α-difluoromethyl-ornithine and Aminoguanidine of pain threshold, morphine analgesia and tolerance
    European Journal of Pharmacology, 2003
    Co-Authors: Bo-yi Qin
    Abstract:

    The effects of alpha-difluoromethyl-ornithine (DFMO) and Aminoguanidine, which might influence the metabolism of endogenous agmatine, on pain threshold, morphine analgesia and tolerance were investigated in mice. In the mouse acetic acid writhing test, intracerebroventricular (i.c.v.) injection of DFMO or Aminoguanidine significantly elevated the pain threshold as indicated by a decrease in the number of writhings. DFMO or Aminoguanidine obviously increased the analgesic effect of morphine in the mouse acetic acid writhing test and the mouse heat radiation tail-flick assay. These effects of DFMO and Aminoguanidine were antagonized by idazoxan (3 mg/kg, i.p.), which is a selective antagonist of the imidazoline receptor. In the mouse heat radiation tail-flick assay, Aminoguanidine significantly prolonged the tail-flick latency of animals, suggesting that the pain threshold was elevated. Furthermore, both DFMO and Aminoguanidine enhanced morphine analgesia and inhibited acute morphine tolerance in the mouse heat radiation tail-flick assay. Neither DFMO nor Aminoguanidine inhibited the activity of nitric oxide synthase in different brain areas in mice in vivo. These results indicate that the substances involved in the metabolism of endogenous agmatine could modulate the pain threshold, morphine analgesia and tolerance, indicating the possible role of endogenous agmatine in the pharmacological effects of morphine.

George Jerums – One of the best experts on this subject based on the ideXlab platform.

  • In Vivo Effects of Aminoguanidine
    Maillard Reactions in Chemistry Food and Health, 2005
    Co-Authors: George Jerums, T. Soulis-liparota, Sianna Panagiotopoulos, Mark E. Cooper
    Abstract:

    Over the last 10 years, the process of advanced glycation endproduct (AGE) formation has been implicated in the pathogenesis of many of the longterm complications of diabetes. Since the restoration of blood glucose levels to normal remains difficult, any treatment which can modify the effects of longterm hyperglycemia represents an attractive option for the prevention of diabetic complications. This report describes the effects of Aminoguanidine on micro- and macroangiopathy in experimental diabetes. Acute effects of Aminoguanidine in the diabetic state have included prevention of the increase in blood flow and permeability in a number of tissues including the eye and kidney. Aminoguanidine has also largely prevented the reduction in motor and sensory nerve conduction velocity and the increased arterial wall protein cross-linking that is observed in diabetes. Several studies have shown that Aminoguanidine prevents the accumulation of AGEs in the kidney, with a concomitant reduction in albuminuria and renal structural changes. With respect to retinopathy, it has been shown that Aminoguanidine prevents the diabetes-induced increase in number of acellular capillaries and reduces the magnitude of pericyte loss. Studies on experimental diabdiabetic neuropathy have demonstrated that Aminoguanidine prevents axonal atrophy and a decrease in nerve conduction velocity. Recently it has also been shown that Aminoguanidine may prevent atherosclerosis in a non-diabetic model of atherosclerosis.

  • relative contributions of advanced glycation and nitric oxide synthase inhibition to Aminoguanidine mediated renoprotection in diabetic rats
    Diabetologia, 1997
    Co-Authors: T Soulis, Mark E. Cooper, Sianna Panagiotopoulos, S Sastra, Vicki Thallas, Ole J Bjerrum, George Jerums
    Abstract:

    Advanced glycation end products (AGEs) have previously been shown to be increased in the diabetic kidney. Aminoguanidine, an inhibitor of advanced glycation, has been shown to attenuate the development of AGEs as well as the progression of renal disease in experimental diabetes. However, the precise mechanisms through which Aminoguanidine acts remain to be elucidated since it is also able to act as an inhibitor of nitric oxide synthase (NOS). This study has therefore compared the effects of Aminoguanidine with the effects of two other inhibitors of NOS, L-NAME and methylguanidine, on the development of experimental diabetic nephropathy. Diabetic rats were randomised to receive no treatment, Aminoguanidine (1 g/l in drinking water), L-NAME (5 mg/l in drinking water) or methylguanidine (1 g/l in drinking water). Diabetic rats had increased levels of albuminuria and urinary nitrite/nitrate excretion when compared to control rats. Renal AGEs measured by fluorescence as well as by a carboxymethyllysine reactive radioimmunoassay, were elevated in diabetic rats. No changes in inducible NOS (iNOS) protein expression were detected in experimental diabetes nor did Aminoguanidine affect iNOS expression. Aminoguanidine did not affect blood glucose or HbA1c but it did prevent increases in albuminuria, urinary nitrites/nitrates and renal AGE levels as measured by fluorescence and radioimmunoassay. L-NAME and methylguanidine did not retard the development of albuminuria, nor did they prevent increases in renal AGE levels, as assessed by fluorescence. However, these treatments did prevent increases in AGEs, as measured by radioimmunoassay. This study indicates that the renoprotective effect of Aminoguanidine in experimental diabetes cannot be reproduced by L-NAME or methylguanidine. It is likely that the effect of Aminoguanidine is mediated predominantly by decreased AGE formation rather than via NOS inhibition. It also raises the possibility that inhibition of fluorescent AGE formation may be more renoprotective than inhibition of the formation of carboxymethyllysine-containing AGEs.

  • Effects of Aminoguanidine in preventing experimental diabetic nephropathy are related to the duration of treatment.
    Kidney international, 1996
    Co-Authors: T Soulis, Mark E. Cooper, Dimitria Vranes, Richard Bucala, George Jerums
    Abstract:

    Effects of Aminoguanidine in preventing experimental diabetic nephropathy are related to the duration of treatment. It has been postulated that the accumulation of advanced glycation end products (AGEs) in the kidney is important in the pathogenesis of diabetic nephropathy. Previously, Aminoguanidine has been shown to inhibit the accumulation of renal AGEs and to retard the development of experimental diabetic nephropathy. The present study serially assessed the accumulation of AGEs in the aorta and kidney, as well as renal functional and structural parameters over 32 weeks of experimental diabetes in the absence and presence of Aminoguanidine. In addition, it was determined if Aminoguanidine was more effective if administered earlier or later in the evolution of diabetic nephropathy by treating diabetic rats with Aminoguanidine in the first or second half of the 32-week study period. In the serial studies, glomerular and renal tubular fluorescence increased over the 32 week period and this increase was attenuated by Aminoguanidine treatment. Concomitant with the effects of Aminoguanidine on fluorescence, there was a retardation in the rise in urinary albumin excretion and prevention of mesangial expansion. Early or late administration of Aminoguanidine in diabetic rats reduced tissue fluorescence in glomeruli and renal tubules. At 32 weeks, renal AGEs were increased in diabetic rats as assessed by tissue fluorescence. Using a specific RIA, renal AGEs were increased in diabetic rats and decreased by Aminoguanidine treatment, administered over the entire 32 weeks or in the first or latter half of the 32-week study period. Aminoguanidine therapy for the entire 32-week study period retarded the rise in albuminuria in the diabetic rats and was more effective than 16 weeks of treatment either in the first or second half of the study. Early and late Aminoguanidine administration were similar in their capacity to retard the development of albuminuria in diabetic rats. Similiar effects were observed on mesangial expansion. The increased glomerular basement thickness in diabetic rats was not affected by Aminoguanidine, irrespective of duration or timing of therapy. This study confirms that in vivo generation of AGEs in the kidney is time dependent and closely linked to the development of experimental diabetic nephropathy. The renoprotective effects of Aminoguanidine in diabetes appear to be related to the duration but not to the timing of treatment.

Timothy S Kern – One of the best experts on this subject based on the ideXlab platform.

  • Diabetes-induced nitrative stress in the retina, and correction by Aminoguanidine
    Journal of Neurochemistry, 2002
    Co-Authors: Yunpeng Du, Mark A. Smith, Casey M. Miller, Timothy S Kern
    Abstract:

    Aminoguanidine inhibits the development of retinopathy in diabetic animals, but the mechanism remains unclear. Inasmuch as Aminoguanidine is a relatively selective inhibitor of the inducible isoform of nitric oxide synthase (iNOS), we have investigated the effects of hyperglycemia on the retinal nitric oxide (NO) pathway in the presence and absence of Aminoguanidine. In vivo studies utilized retinas from experimentally diabetic rats treated or without Aminoguanidine for 2 months, and in vitro studies used bovine retinal endothelial cells and a transformed retinal glial cell line (rMC-1) incubated in 5 mm and 25 mm glucose with and without Aminoguanidine (100 microg/mL). NO was detected as nitrite and nitrate, and nitrotyrosine and iNOS were detected using immunochemical methods. Retinal homogenates from diabetic animals had greater than normal levels of NO and iNOS (p < 0.05), and nitrotyrosine was greater than normal, especially in one band immunoprecipitated from retinal homogenates. Oral Aminoguanidine significantly inhibited all of these increases. Nitrotyrosine was detected immunohistochemically only in the retinal vasculature of non-diabetic and diabetic animals. Retinal endothelial and rMC-1 cells cultured in high glucose increased NO and NT, and Aminoguanidine inhibited both increases in rMC-1 cells, but only NT in endothelial cells. Hyperglycemia increases NO production in retinal cells, and Aminoguanidine can inhibit this abnormality. Inhibition of diabetic retinopathy by Aminoguanidine might be mediated in part by inhibition of sequelae of NO production.

  • Diabetes-induced nitrative stress in the retina, and correction by Aminoguanidine.
    Journal of neurochemistry, 2002
    Co-Authors: Mark A. Smith, C. Miller, Timothy S Kern
    Abstract:

    Aminoguanidine inhibits the development of retinopathy in diabetic animals, but the mechanism remains unclear. Inasmuch as Aminoguanidine is a relatively selective inhibitor of the inducible isoform of nitric oxide synthase (iNOS), we have investigated the effects of hyperglycemia on the retinal nitric oxide (NO) pathway in the presence and absence of Aminoguanidine. In vivo studies utilized retinas from experimentally diabetic rats treated or without Aminoguanidine for 2 months, and in vitro studies used bovine retinal endothelial cells and a transformed retinal glial cell line (rMC-1) incubated in 5 mm and 25 mm glucose with and without Aminoguanidine (100 µg/mL). NO was detected as nitrite and nitrate, and nitrotyrosine and iNOS were detected using immunochemical methods. Retinal homogenates from diabetic animals had greater than normal levels of NO and iNOS (p 

  • Pharmacological Inhibition of Diabetic Retinopathy: Aminoguanidine and Aspirin
    Diabetes, 2001
    Co-Authors: Timothy S Kern, Ronald L. Engerman
    Abstract:

    Effects of Aminoguanidine and aspirin on the development of retinopathy have been examined in 5-year studies of diabetic dogs. Either agent was administered daily in doses of 20-25 mg. kg(-1). day(-1). Because severity of hyperglycemia greatly influences development of the retinopathy, special effort was devoted to maintaining comparable glycemia in experimental and control groups. The retinal vasculature was isolated by the trypsin digest method, and retinopathy was assessed by light microscopy. Diabetes for 5 years resulted, as expected, in saccular capillary aneurysms, pericyte ghosts, acellular capillaries, retinal hemorrhages, and other lesions. Administration of Aminoguanidine essentially prevented the retinopathy, significantly inhibiting the development of retinal microaneurysms, acellular capillaries, and pericyte ghosts compared with diabetic controls. Aspirin significantly inhibited the development of retinal hemorrhages and acellular capillaries over the 5 years of study, but had less effect on other lesions. Although diabetes resulted in significantly increased levels of advanced glycation end products (AGEs) (namely, pentosidine in tail collagen and aorta, and Hb-AGE), Aminoguanidine had no significant influence on these parameters of glycation. Nitration of a retinal protein was significantly increased in diabetes and inhibited by Aminoguanidine. The biochemical mechanism by which Aminoguanidine has inhibited retinopathy thus is not clear. Aminoguanidine (but not aspirin) inhibited a diabetes-induced defect in ulnar nerve conduction velocity, but neither agent was found to influence kidney structure or albumen excretion.

A Love – One of the best experts on this subject based on the ideXlab platform.

  • effects of Aminoguanidine on peripheral nerve function and polyol pathway metabolites in streptozotocin diabetic rats
    Diabetologia, 1992
    Co-Authors: Norman E Cameron, Mary A Cotter, K C Dines, A Love
    Abstract:

    The effect of 2 months Aminoguanidine treatment on nerve conduction abnormalities was studied in streptozotocin-diabetic rats. Treatment with Aminoguanidine from the induction of diabetes mellitus prevented a 22% decrease in sciatic motor nerve conduction velocity (p <0.001), and a 10% deficit in sensory saphenous conduction velocity (p <0.01). There was a 49% increase in resistance of sciatic nerve to hypoxic conduction failure in vitro. This was not significantly affected by Aminoguanidine treatment. Sciatic nerve polyol pathway metabolites, sorbitol and fructose, were elevated 10-fold by diabetes (p <0.001). Myo-inosinositol levels were 18% decreased by diabetes. Aminoguanidine treatment had no significant effect on sorbitol, fructose or myo-inosinositol levels. Aminoguanidine has been identified as both an inhibitor of the formation of advanced glycation end products, and an aldose reductase inhibitor. The data suggest that beneficial actions on nerve function do not depend on the latter property. They support the notion that advanced glycation end products contribute to the aetiology of early diabetic neuropathy, possibly acting via a vascular mechanism, and that Aminoguanidine treatment may have therapeutic applications.

  • Effects of Aminoguanidine on peripheral nerve function and polyol pathway metabolites in streptozotocin-diabetic rats.
    Diabetologia, 1992
    Co-Authors: Norman E Cameron, Mary A Cotter, K C Dines, A Love
    Abstract:

    The effect of 2 months Aminoguanidine treatment on nerve conduction abnormalities was studied in streptozotocin-diabetic rats. Treatment with Aminoguanidine from the induction of diabetes mellitus prevented a 22% decrease in sciatic motor nerve conduction velocity (p

Mark E. Cooper – One of the best experts on this subject based on the ideXlab platform.

  • In Vivo Effects of Aminoguanidine
    Maillard Reactions in Chemistry Food and Health, 2005
    Co-Authors: George Jerums, T. Soulis-liparota, Sianna Panagiotopoulos, Mark E. Cooper
    Abstract:

    Over the last 10 years, the process of advanced glycation endproduct (AGE) formation has been implicated in the pathogenesis of many of the longterm complications of diabetes. Since the restoration of blood glucose levels to normal remains difficult, any treatment which can modify the effects of longterm hyperglycemia represents an attractive option for the prevention of diabetic complications. This report describes the effects of Aminoguanidine on micro- and macroangiopathy in experimental diabetes. Acute effects of Aminoguanidine in the diabetic state have included prevention of the increase in blood flow and permeability in a number of tissues including the eye and kidney. Aminoguanidine has also largely prevented the reduction in motor and sensory nerve conduction velocity and the increased arterial wall protein cross-linking that is observed in diabetes. Several studies have shown that Aminoguanidine prevents the accumulation of AGEs in the kidney, with a concomitant reduction in albuminuria and renal structural changes. With respect to retinopathy, it has been shown that Aminoguanidine prevents the diabetes-induced increase in number of acellular capillaries and reduces the magnitude of pericyte loss. Studies on experimental diabetic neuropathy have demonstrated that Aminoguanidine prevents axonal atrophy and a decrease in nerve conduction velocity. Recently it has also been shown that Aminoguanidine may prevent atherosclerosis in a non-diabetic model of atherosclerosis.

  • relative contributions of advanced glycation and nitric oxide synthase inhibition to Aminoguanidine mediated renoprotection in diabetic rats
    Diabetologia, 1997
    Co-Authors: T Soulis, Mark E. Cooper, Sianna Panagiotopoulos, S Sastra, Vicki Thallas, Ole J Bjerrum, George Jerums
    Abstract:

    Advanced glycation end products (AGEs) have previously been shown to be increased in the diabetic kidney. Aminoguanidine, an inhibitor of advanced glycation, has been shown to attenuate the development of AGEs as well as the progression of renal disease in experimental diabetes. However, the precise mechanisms through which Aminoguanidine acts remain to be elucidated since it is also able to act as an inhibitor of nitric oxide synthase (NOS). This study has therefore compared the effects of Aminoguanidine with the effects of two other inhibitors of NOS, L-NAME and methylguanidine, on the development of experimental diabetic nephropathy. Diabetic rats were randomised to receive no treatment, Aminoguanidine (1 g/l in drinking water), L-NAME (5 mg/l in drinking water) or methylguanidine (1 g/l in drinking water). Diabetic rats had increased levels of albuminuria and urinary nitrite/nitrate excretion when compared to control rats. Renal AGEs measured by fluorescence as well as by a carboxymethyllysine reactive radioimmunoassay, were elevated in diabetic rats. No changes in inducible NOS (iNOS) protein expression were detected in experimental diabetes nor did Aminoguanidine affect iNOS expression. Aminoguanidine did not affect blood glucose or HbA1c but it did prevent increases in albuminuria, urinary nitrites/nitrates and renal AGE levels as measured by fluorescence and radioimmunoassay. L-NAME and methylguanidine did not retard the development of albuminuria, nor did they prevent increases in renal AGE levels, as assessed by fluorescence. However, these treatments did prevent increases in AGEs, as measured by radioimmunoassay. This study indicates that the renoprotective effect of Aminoguanidine in experimental diabetes cannot be reproduced by L-NAME or methylguanidine. It is likely that the effect of Aminoguanidine is mediated predominantly by decreased AGE formation rather than via NOS inhibition. It also raises the possibility that inhibition of fluorescent AGE formation may be more renoprotective than inhibition of the formation of carboxymethyllysine-containing AGEs.

  • Effects of Aminoguanidine in preventing experimental diabetic nephropathy are related to the duration of treatment.
    Kidney international, 1996
    Co-Authors: T Soulis, Mark E. Cooper, Dimitria Vranes, Richard Bucala, George Jerums
    Abstract:

    Effects of Aminoguanidine in preventing experimental diabetic nephropathy are related to the duration of treatment. It has been postulated that the accumulation of advanced glycation end products (AGEs) in the kidney is important in the pathogenesis of diabetic nephropathy. Previously, Aminoguanidine has been shown to inhibit the accumulation of renal AGEs and to retard the development of experimental diabetic nephropathy. The present study serially assessed the accumulation of AGEs in the aorta and kidney, as well as renal functional and structural parameters over 32 weeks of experimental diabetes in the absence and presence of Aminoguanidine. In addition, it was determined if Aminoguanidine was more effective if administered earlier or later in the evolution of diabetic nephropathy by treating diabetic rats with Aminoguanidine in the first or second half of the 32-week study period. In the serial studies, glomerular and renal tubular fluorescence increased over the 32 week period and this increase was attenuated by Aminoguanidine treatment. Concomitant with the effects of Aminoguanidine on fluorescence, there was a retardation in the rise in urinary albumin excretion and prevention of mesangial expansion. Early or late administration of Aminoguanidine in diabetic rats reduced tissue fluorescence in glomeruli and renal tubules. At 32 weeks, renal AGEs were increased in diabetic rats as assessed by tissue fluorescence. Using a specific RIA, renal AGEs were increased in diabetic rats and decreased by Aminoguanidine treatment, administered over the entire 32 weeks or in the first or latter half of the 32-week study period. Aminoguanidine therapy for the entire 32-week study period retarded the rise in albuminuria in the diabetic rats and was more effective than 16 weeks of treatment either in the first or second half of the study. Early and late Aminoguanidine administration were similar in their capacity to retard the development of albuminuria in diabetic rats. Similiar effects were observed on mesangial expansion. The increased glomerular basement thickness in diabetic rats was not affected by Aminoguanidine, irrespective of duration or timing of therapy. This study confirms that in vivo generation of AGEs in the kidney is time dependent and closely linked to the development of experimental diabetic nephropathy. The renoprotective effects of Aminoguanidine in diabetes appear to be related to the duration but not to the timing of treatment.