Inhibition of development of peripheral neuropathy in streptozotocin-induced diabetic rats with N-acetylcysteine

Sagara, Mikio; Satoh, Jo; Wada, Reona; Yagihashi, Soroku; Takahashi, K.; Fukuzawa, Masahiro; Muto, Gen; Muto, Yuko; Toyota, Takayoshi

doi:10.1007/s001250050440

Cited by 27 publications

(31 citation statements)

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“…NAC and ALA are known to act as potent antioxidants in diabetic complication (Maritim et al 2003;Sagara et al 1996). Our previous study also demonstrated that NAC prevents oxidative cell damage of HIT-T15 pancreatic beta cell induced by the reducing sugar 2-deoxy-D-ribose (Koh et al 2005).…”

Section: Discussionmentioning

confidence: 93%

Prooxidative effects of green tea polyphenol (−)-epigallocatethin-3-gallate on the HIT-T15 pancreatic beta cell line

Suh

Chon

et al. 2009

Cell Biol Toxicol

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Epigallocatechin-3-gallate (EGCG) is the main polyphenolic constituent in green tea and is believed to function as an antioxidant. However, increasing evidence indicates that EGCG produces reactive oxygen species (ROS) and subsequent cell death. In this study, we investigated the prooxidative effects of EGCG on the HIT-T15 pancreatic beta cell line. Dose-dependent cell viability was monitored with the cell counting kit-8 assay, while the induction of apoptosis was analyzed by a cell death ELISA kit and comet assay. Extracellular H(2)O(2) was determined using the Amplex Red Hydrogen Peroxide Assay Kit. Intracellular oxidative stress was measured by fluorometric analysis of 2',7'-dichlorofluorescin (DCFH) oxidation using DCFH diacetate (DA) as the probe. Treatment with EGCG (5-100 microM) decreased the viability of pancreatic beta cells, caused concomitant increases in apoptotic cell death, and increased the production of H(2)O(2) and ROS. Catalase, the iron-chelating agent diethylenetriaminepentaacetic acid, and the Fe(II)-specific chelator o-phenanthroline all suppressed the effects of EGCG, indicating the involvement of both H(2)O(2) and Fe(II) in the mechanism of action of EGCG. The antioxidant N-acetyl-cysteine and alpha-lipoic acid also suppressed the effects of EGCG. Furthermore, EGCG did not scavenge exogenous H(2)O(2), but rather, it synergistically increased H(2)O(2)-induced oxidative cell damage in pancreatic beta cells. Together, these findings suggest that in the HIT-T15 pancreatic beta cell line, EGCG mediated the generation of H(2)O(2), triggering Fe(II)-dependent formation of a highly toxic radical that in turn induced oxidative cell damage.

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Section: Discussionmentioning

confidence: 93%

Prooxidative effects of green tea polyphenol (−)-epigallocatethin-3-gallate on the HIT-T15 pancreatic beta cell line

Suh

Chon

et al. 2009

Cell Biol Toxicol

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“…The effects of ARIs on indices of DN are unidirectional with those of inhibitors of nonenzymatic glycation (57,65,77) and PKC (62,78) as well as antioxidants (31,55,64,70,(79)(80)(81)(82)(83). Over past several years, the continuing debate about a "primary mechanism" of diabetic complications has centered on oxidative stress and its relationship with other hyperglycemiainitiated factors (84).…”

Section: Discussionmentioning

confidence: 99%

An aldose reductase inhibitor reverses early diabetes‐induced changes in peripheral nerve function, metabolism, and antioxidative defense

et al. 2001

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Aldose reductase inhibitors (ARIs) prevent peripheral nerve dysfunction and morphological abnormalities in diabetic animal models. However, some experimental intervention studies and clinical trials of ARIs on diabetic neuropathy appeared disappointing because of either 1) their inadequate design and, in particular, insufficient correction of the sorbitol pathway activity or 2) the inability to reverse established functional and metabolic deficits of diabetic neuropathy by AR inhibition in general. We evaluated whether diabetes-induced changes in nerve function, metabolism, and antioxidative defense are corrected by the dose of ARI (sorbinil, 65 mg/kg/d in the diet), resulting in complete inhibition of increased sorbitol pathway activity. The groups included control rats and streptozotocin-diabetic rats treated with/without ARI for 2 weeks after 4 weeks of untreated diabetes. ARI treatment corrected diabetes-induced nerve functional changes; that is, decrease in endoneurial nutritive blood flow, motor and sensory nerve conduction velocities, and metabolic abnormalities (i.e., mitochondrial and cytosolic NAD+/NADH redox imbalances and energy deficiency). ARI restored nerve concentrations of two major non-enzymatic antioxidants, reduced glutathione (GSH) and ascorbate, and completely arrested diabetes-induced lipid peroxidation. In conclusion, treatment with adequate doses of ARIs (that is, doses that completely inhibit increased sorbitol pathway activity) is an effective approach for reversal of, at least, early diabetic neuropathy.

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“…substance P and neuropeptide Y deficits in the sciatic nerve that were, at least partially, counteracted by α-lipoic acid [208]; 2) taurine alleviated oxidative stress and prevented diabetes-induced nerve growth factor deficit in the sciatic nerve of STZ-diabetic rats [191]. Several studies implicate oxidative/nitrosative stress in morphological abnormalities characteristic for PDN as well as neuronal apoptosis [177,179,209] Despite evidence for an important role of oxidative/nitrosative stress in the pathogenesis of experimental PDN, conventional antioxidants (e.g., lipoic acid) have modest [186,187] effect on clinical neuropathy. Note, that in animal studies, such conventional antioxidants as vitamin E, butylated hydroxytoluene and N-acetyl-L-cysteine had to be administered at extremely high doses of 0.5-1 g/kg body weight per day to produce effect on PDN.…”

Section: Diabetic Neuropathymentioning

confidence: 97%

Role for Poly(ADP-ribose) Polymerase Activation in Diabetic Nephropathy, Neuropathy and Retinopathy

Obrosova

Julius²

2005

CVP

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Chronic complications of diabetes mellitus e.a. diabetic nephropathy, neuropathy and retinopathy develop in at least 30-50% of patients with both Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetes, and are the major cause of increased morbidity and mortality. The ultimate consequences of diabetes complications include renal failure, foot ulceration and amputation, and blindness. The magnitude of the problem and its economic impact make extremely important to understand the natural history of chronic diabetes complications and to identify more successful preventive and therapeutic options. The pathogenesis of diabetes complications involves multiple mechanisms. The importance of vascular component is well recognized in diabetic retinopathy, which is primarily a vascular disease, as well as diabetic nephropathy developing as a result of complex interplay between hemodynamic and metabolic factors. The importance of vascular versus non-vascular mechanisms in the pathogenesis of diabetic neuropathy remains a subject of debate. Studies in animal and cell culture models revealed that such mechanisms as increased aldose reductase activity, non-enzymatic glycation/glycoxidation, activation of protein kinase C, impaired growth factor support, enhanced oxidative/nitrosative stress, and its downstream effectors such as mitogen-activated protein kinase activation, inflammatory response, endothelin-1 overexpression and impaired Ca(++) signaling, play an important role in all three tissue-targets for diabetes complications i.e. kidney, retina and peripheral nerve. Evidence for important role of the downstream effector of free radical and oxidant-induced DNA injury, poly(ADP-ribose) polymerase activation, is emerging. This review describes recent studies addressing the role for poly(ADP-ribose) polymerase activation in diabetic nephropathy, neuropathy and retinopathy.

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Inhibition of development of peripheral neuropathy in streptozotocin-induced diabetic rats with N-acetylcysteine

Cited by 27 publications

References 0 publications

Prooxidative effects of green tea polyphenol (−)-epigallocatethin-3-gallate on the HIT-T15 pancreatic beta cell line

Prooxidative effects of green tea polyphenol (−)-epigallocatethin-3-gallate on the HIT-T15 pancreatic beta cell line

An aldose reductase inhibitor reverses early diabetes‐induced changes in peripheral nerve function, metabolism, and antioxidative defense

Role for Poly(ADP-ribose) Polymerase Activation in Diabetic Nephropathy, Neuropathy and Retinopathy

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