Comparison of the effects of aminoguanidine and L-carnitine treatments on somatosensorial evoked potentials in alloxan-diabetic rats

Yıldız, Oğuzhan; Özata, Metịn; Ozkardes, Abdullah; Deniz, Gönen; Yildirimkaya, Metin; Çorakçı, Ahmet; Yardim, M.; Gündoğan, Mehmet

doi:10.1007/bf00168446

Cited by 9 publications

(8 citation statements)

References 47 publications

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“…In this study we found that treatment of STZ-diabetic rats with Ag (1g/L/day, equivalent to 0.8 g/kg/day) for six weeks via drinking water, starting two weeks after the onset of diabetes , did not alter either the ventricular composition of MHC or serum T3 levels. Consistent with an earlier report (46), Ag treatment significantly reduced circulating levels of thiobarbituric acid reactants (mainly malondialdehyde and other RCS) and attenuated the increase in SSAO activity induced by diabetes (45). Ag treatment also blunted actomyosin Ca 2+ -sensitive ATPase activity loss and ATP-stimulated syneresis.…”

Section: Discussionsupporting

confidence: 91%

Carbonylation of myosin heavy chains in rat heart during diabetes

Shao

Rozanski

Nagai

et al. 2010

Biochemical Pharmacology

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Cardiac inotropy progressively declines during diabetes mellitus. To date, the molecular mechanisms underlying this defect remain incompletely characterized. This study tests the hypothesis that ventricular myosin heavy chains (MHC) undergo carbonylation by reactive carbonyl species (RCS) during diabetes and these modifications contribute to the inotropic decline. Male Sprague-Dawley rats were injected with streptozotocin (STZ). Fourteen days later animals were divided into two groups: one group was treated with the RCS blocker aminoguanidine for six weeks, while the other group received no treatment. After eight weeks of diabetes, cardiac ejection fraction, fractional shortening, left ventricular pressure development (+dP/dt) and myocyte shortening were decreased by 9%, 16%, 34% and 18%, respectively. Ca 2+ -and Mg 2+ -actomyosin ATPase activities and peak actomyosin syneresis were also reduced by 35%, 28%, and 72%. MHC-α to MHC-β ratio was 12:88. Mass spectrometry and Western blots revealed the presence of carbonyl adducts on MHC-α and MHC-β. Aminoguandine treatment did not alter MHC composition, but it blunted formation of carbonyl adducts and decreases in actomyosin Ca 2+ -sensitive ATPase activity, syneresis, myocyte shortening, cardiac ejection fraction, fractional shortening and +dP/dt induced by diabetes. From these new data it can be concluded that in addition to isozyme switching, modification of MHC by RCS also contributes to the inotropic decline seen during diabetes.

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Section: Discussionsupporting

confidence: 91%

Carbonylation of myosin heavy chains in rat heart during diabetes

Shao

Rozanski

Nagai

et al. 2010

Biochemical Pharmacology

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“…There was no effect on the elevated conjugated diene levels in the sciatic nerves of diabetic rats,27 and aminoguanidine did not reduce elevated superoxide production by sciatic nerve epineurial blood vessels 45. However, a diabetes‐induced increase in brain thiobarbituric acid reactants was reduced 31. Thus, although there are interpretational issues due to aminoguanidine's specificity, the balance of evidence suggests that AGE/ALE formation is likely to play a role in diabetic neurovascular dysfunction.…”

Section: Effects Of Aminoguanidine On the Neurovascular Systemmentioning

confidence: 93%

“…Aminoguanidine also improved central neurotransmission, partially correcting an increase in somatosensory-evoked potential latency in diabetic rats. 31 In nonrodent models, aminoguanidine had no effect on NCV over a five year period in diabetic baboons. 32 However, the dose employed (10 mg/kg) was only marginally effective in diabetic rats, 33 and a higher dose (25 mg/kg) prevented the development of ulnar nerve NCV deficits in diabetic dogs over a period of five years.…”

Section: Effects Of Aminoguanidine On the Neurovascular Systemmentioning

confidence: 94%

“…The swiftness of this correction suggests that intracellular AGE/ALE generation was the major contributor to dysfunction rather than the slower accumulation of extracellular products on long‐lived proteins. Aminoguanidine also improved central neurotransmission, partially correcting an increase in somatosensory‐evoked potential latency in diabetic rats 31. In nonrodent models, aminoguanidine had no effect on NCV over a five year period in diabetic baboons 32.…”

Section: Effects Of Aminoguanidine On the Neurovascular Systemmentioning

confidence: 95%

“…45 However, a diabetes-induced increase in brain thiobarbituric acid reactants was reduced. 31 Thus, although there are interpretational issues due to aminoguanidine's specificity, the balance of evidence suggests that AGE/ALE formation is likely to play a role in diabetic neurovascular dysfunction. This conclusion can be strengthened if other compounds and AGE/ALE-reducing strategies give similar benefits.…”

Section: Effects Of Aminoguanidine On the Neurovascular Systemmentioning

confidence: 99%

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Inhibitors of Advanced Glycation End Product Formation and Neurovascular Dysfunction in Experimental Diabetes

Cameron

Gibson

Nangle

et al. 2005

Annals of the New York Academy of Sciences

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Advanced glycation and lipoxidation end products (AGEs/ALEs) have been implicated in the pathogenesis of the major microvascular complications of diabetes mellitus: nephropathy, neuropathy, and retinopathy. This article reviews the evidence regarding the peripheral nerve and its vascular supply. Most investigations done to assess the role of AGEs/ALEs in animal models of diabetic neuropathy have used aminoguanidine as a prototypic inhibitor. Preventive or intervention experiments have shown treatment benefits for motor and sensory nerve conduction velocity, autonomic nitrergic neurotransmission, nerve morphometry, and nerve blood flow. The latter depends on improvements in nitric oxide-mediated endothelium-dependent vasodilation and is responsible for conduction velocity improvements. A mechanistic interpretation of aminoguanidine's action in terms of AGE/ALE inhibition is made problematic by the relative lack of specificity. However, other unrelated compounds, such as pyridoxamine and pyridoxamine analogues, have recently been shown to have beneficial effects similar to aminoguanidine, as well as to improve pain-related measures of thermal hyperalgesia and tactile allodynia. These data also stress the importance of redox metal ion-catalyzed AGE/ALE formation. A further approach is to decrease substrate availability by reducing the elevated levels of hexose and triose phosphates found in diabetes. Benfotiamine is a transketolase activator that directs these substrates to the pentose phosphate pathway, thus reducing tissue AGEs. A similar spectrum of improvements in nerve and vascular function were noted when using benfotiamine in diabetic rats. Taken together, the data provide strong support for an important role for AGEs/ALEs in the etiology of diabetic neuropathy.

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