Effects of natural free radical scavengers on peripheral nerve and neurovascular function in diabetic rats

Cotter, Mary A.; Love, A.; Watt, Matthew J.; Cameron, Norman E.; Dines, K. C.

doi:10.1007/bf00401760

Cited by 108 publications

(55 citation statements)

References 54 publications

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“…Some previous studies of VitE in STZ-induced diabetes have failed to show any significant effect on endothelium-dependent relaxation in the mesenteric arteries, although in those studies a five-to ten-fold lower dose of VitE was used [9]. Indeed, supplementation with a higher dose of VitE improved endotheliumdependent relaxation in the aorta [8] and prevented the decline in blood flow to hindlimb nerves after 2 months of STZ-induced diabetes [22], similar to our present findings in small resistance arteries.…”

Section: Discussionmentioning

confidence: 99%

Early vitamin E supplementation attenuates diabetes-associated vascular dysfunction and the rise in protein kinase C-β in mesenteric artery and ameliorates wall stiffness in femoral artery of Wistar rats

et al. 2004

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Aims/hypothesis. The impact of early vitamin E supplementation on vascular function in diabetes remains unresolved. Therefore, we examined the effects of vitamin E on functional and structural parameters and on chemical markers that are disturbed in diabetes in mesenteric and femoral arteries. Methods. Segments of both arteries, taken from control and 8-week-old streptozotocin diabetic Wistar rats that were treated or not with vitamin E, were mounted on wire and pressure myographs, after which endothelium-dependent and -independent vasodilation was assessed. Passive mechanical wall properties and the localisation and levels of protein kinase C (PKC)-β 2 and AGE were evaluated in these vessels. Results. Vitamin E supplementation was associated with improved endothelium-dependent and -independent vasodilatation in mesenteric arteries from diabetic rats. Impaired endothelium-dependent vasodilatation in diabetic mesenteric vessels was associated with PKC-β 2 up-regulation and this was prevented by vitamin E supplementation. Increased AGE accumulation and plasma isoprostane levels in diabetic rats were not changed by vitamin E. In the femoral artery, vitamin E supplementation had no effect on endothelium-dependent or -independent vasodilatation, but did prevent the wall stiffening associated with diabetes. Conclusions/interpretation. Early vitamin E supplementation has a beneficial effect on diabetes-induced endothelial dysfunction in resistance arteries. This benefit may arise from a direct effect on smooth muscle function, as a result of inhibition of the PKC-β 2 isoform by vitamin E. Abbreviations: ACh, acetylcholine · EDHF, endothelium-derived hyperpolarising factor · GHb, glycohaemoglobin · h, wall thickness · ID, internal diameter · L, length · l-NAME, N ω -nitro-L-arginine methyl ester · NO, nitric oxide · OD, outside diameter · P, intraluminal pressure · PKC, protein kinase C · PSS, physiological saline solution · SNP, sodium nitroprusside · STZ, streptozotocin · VitE, vitamin E supplementation · V max , maximal relaxation

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Section: Discussionmentioning

confidence: 99%

Early vitamin E supplementation attenuates diabetes-associated vascular dysfunction and the rise in protein kinase C-β in mesenteric artery and ameliorates wall stiffness in femoral artery of Wistar rats

et al. 2004

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“…Motor conduction velocity was measured between sciatic notch and knee for the nerve branch to tibialis anterior muscle as previously described [6]. In a subset of rats not used for blood flow determination, sensory NCV in saphenous nerve was also estimated [24].…”

Section: Methodsmentioning

confidence: 99%

“…This would result in an apparent relative decrease in nerve blood flow for diabetic rats. However, the application of the microsphere method to the measurement of nerve blood flow is questionable [24,27,28,41] and other techniques that do not involve nerve exposure also show reduced nerve blood flow in diabetic rats [42]. Whether or not an operative procedure causes a significant inflammatory response depends critically on the degree of tissue trauma.…”

Section: Methodsmentioning

confidence: 99%

“…NADPH is also necessary for nitric oxide synthesis and the maintenance of vascular tone. These latter mechanisms have been linked to reduced nerve perfusion and oxygen supply [6,10,[23][24][25][26] which make major contributions to nerve dysfunction in diabetic patients and experimental models [27][28][29]. In contrast, other hypotheses consider the second half of the polyol pathway, conversion of sorbitol to fructose by sorbitol dehydrogenase, as the most important in the pathogenesis of diabetic complications including neuropathy.…”

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Comparison of the effects of inhibitors of aldose reductase and sorbitol dehydrogenase on neurovascular function, nerve conduction and tissue polyol pathway metabolites in streptozotocin-diabetic rats

et al. 1997

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Elevated polyol pathway activity has been implicated in the development of diabetic complications, including neuropathy [1]. In diabetic models, inhibitors of the first enzyme in the pathway, aldose reductase, prevent or correct nerve conduction velocity (NCV) and regeneration deficits [2][3][4][5][6][7][8][9][10][11][12][13]. Clinical trials of aldose reductase inhibitors (ARIs) have shown modest improvements in neurological symptoms, NCV, sensory measures, and an increase in nerve fibre regeneration [14-17] despite a less effective polyol pathway blockade than was found necessary for functional effects in animal studies [6,10,18].Several hypotheses have been advanced to explain the action of ARI. Some putative mechanisms are primarily dependent on the first half of the polyol pathway, conversion of glucose to sorbitol by aldose Diabetologia (1997) 40: 271-281 Comparison of the effects of inhibitors of aldose reductase and sorbitol dehydrogenase on neurovascular function, nerve conduction and tissue polyol pathway metabolites in streptozotocin-diabetic rats Summary Aldose reductase inhibitors (ARIs) attenuate diabetic complications in several tissues, including lens, retina, kidney, blood vessels, striated muscle and peripheral nerve. However, it is unclear whether their action in diabetes mellitus depends directly on inhibiting the conversion of glucose to sorbitol by aldose reductase or indirectly by reducing the sorbitol available for subsequent metabolism to fructose by sorbitol dehydrogenase. To identify the polyol pathway step most relevant to complications, particularly neuropathy, we compared the biochemical effects of a sorbitol dehydrogenase inhibitor, WAY-135 706, (250 mg ⋅ kg −1 ⋅ day −1 ) and an ARI, WAY-121 509, (10 mg ⋅ kg −1 ⋅ day −1 ) on a variety of tissues, and their effects on nerve perfusion and conduction velocity. After 6 weeks of untreated streptozotocin diabetes, rats were treated for 2 weeks. Sorbitol was elevated 2.1-32.6-fold by diabetes in lens, retina, kidney, aorta, diaphragm, erythrocytes and sciatic nerve; this was further increased (1.6-8.2-fold) by WAY-135 706 whereas WAY-121 509 caused a marked reduction. Fructose 1.6-8.0-fold elevated by diabetes in tissues other than diaphragm, was reduced by WAY-135 706 and WAY-121 509, except in the kidney. Motor and sensory nerve conduction velocities were decreased by 20.2 and 13.9 %, respectively with diabetes. These deficits were corrected by WAY-121 509, but WAY-135 706 was completely ineffective. A 48.6 % diabetes-induced deficit in sciatic nutritive endoneurial blood flow was corrected by WAY-121 509, but was unaltered by WAY-135 706. Thus, despite profound sorbitol dehydrogenase inhibition, WAY-135 706 had no beneficial effect on nerve function. The data demonstrate that aldose reductase activity, the first step in the polyol pathway, makes a markedly greater contribution to the aetiology of diabetic neurovascular and neurological dysfunction than does the second step involving sorbitol dehydrogenase. [Diabetologia (1997) 40: ...

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“…Cotter et al (11) also studied vitamin E (1000 mg/kg body weight). They demonstrated prevention in the DM-induced alterations in motor nerve conduction velocity.…”

Section: Discussionmentioning

confidence: 99%

Supplementation with 0.1% and 2% vitamin e in diabetic rats: analysis of myenteric neurons immunostained for myosin-V and nNOS in the jejunum

Tronchini

Trevizan

Tashima

et al. 2012

Arq. Gastroenterol.

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-Context -Diabetes mellitus is a disease characterized by hyperglycemia that, when allowed to progress long-term untreated, develops vascular and neurological complications, which are responsible for the development of alterations in the enteric nervous system in diabetic patients. In the gastrointestinal tract, diabetes mellitus promotes motor and sensory changes, and in the reflex function of this system, causing gastroparesis, diarrhea, constipation, megacolon, slow gastrointestinal transit, gastric stasis and dilation with decreased or increased peristaltic contractions. Several studies have shown that oxidative stress is the main responsible for the vascular and neurological complications affecting the enteric nervous system of diabetics. Objective -The effects of 0.1% and 2% vitamin E on myosin-V-and nNOS-immunoreactive neurons in the jejunum of diabetic rats were investigated. Methods -Thirty rats were divided into the groups: normoglycemic, normoglycemic treated with 0.1% vitamin E, normoglycemic treated with 2% vitamin E, diabetic, diabetic treated with 0.1% vitamin E, and diabetic treated with 2% vitamin E. The neuronal density and areas of neuron cell bodies were determined. Results -Diabetes (diabetic group) significantly reduced the number of myosin-V-immunoreactive neurons compared with the normoglycemic group. The diabetic treated with 0.1% vitamin E and diabetic treated with 2% vitamin E groups did not exhibit a greater density than the D group (P>0.05). Nitrergic density did not change with diabetes (P>0.05). The areas of myosin-V-and nNOS-immunoreactive neurons significantly increased in the normoglycemic treated with 2% vitamin E and diabetic groups compared with the normoglycemic group. Conclusion -Supplementation with 2% vitamin E had a neurotrophic effect only in the area of myosin-V-immunoreactive neurons compared with the diabetic group. HEADINGS -Vitamin E. Diabetes mellitus, experimental. Jejunum. Neurons. Myosin type V. Nitric oxide sinthase. Rats.

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Effects of natural free radical scavengers on peripheral nerve and neurovascular function in diabetic rats

Cited by 108 publications

References 54 publications

Early vitamin E supplementation attenuates diabetes-associated vascular dysfunction and the rise in protein kinase C-β in mesenteric artery and ameliorates wall stiffness in femoral artery of Wistar rats

Early vitamin E supplementation attenuates diabetes-associated vascular dysfunction and the rise in protein kinase C-β in mesenteric artery and ameliorates wall stiffness in femoral artery of Wistar rats

Comparison of the effects of inhibitors of aldose reductase and sorbitol dehydrogenase on neurovascular function, nerve conduction and tissue polyol pathway metabolites in streptozotocin-diabetic rats

Supplementation with 0.1% and 2% vitamin e in diabetic rats: analysis of myenteric neurons immunostained for myosin-V and nNOS in the jejunum

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