Effects of OPB‐9195, anti‐glycation agent, on experimental diabetic neuropathy

Wada, Ryuichi; Nishizawa, Yusuke; Yagihashi, Norito; Takeuchi, Masayoshi; Ishikawa, Yuichi; Yasumura, Koichi; Nakano, Masahiko; Yagihashi, Soroku

doi:10.1046/j.1365-2362.2001.00826.x

Cited by 92 publications

(77 citation statements)

References 46 publications

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“…A variety of mechanisms have been implicated in the pathogenesis of PDN, including increased aldose reductase activity (19 -21), nonenzymatic glycation/glycoxidation (18,22,23), activation of protein kinase C (24), impaired neurotrophic support (25,26), and enhanced oxidative-nitrosative stress (9 -13,27) and, recently, downstream effectors of free radical and oxidant-induced injury, i.e., mitogen-activated protein kinase (MAPK) activation (28), PARP activation (3,8), and impaired calcium signaling (29). All of these mechanisms have been demonstrated to contribute to early PDN and to cause motor and sensory nerve conduction deficits, neurovascular dysfunction, altered sensation, and diabetic neuropathic pain.…”

Section: Discussionmentioning

confidence: 99%

Low-Dose Poly(ADP-Ribose) Polymerase Inhibitor-Containing Combination Therapies Reverse Early Peripheral Diabetic Neuropathy

Drel

Szabó

et al. 2005

Diabetes

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Poly(ADP-ribose) polymerase (PARP) inhibition has recently been identified as a novel approach to treatment of experimental peripheral diabetic neuropathy (PDN). (5); 2) changes in transcriptional regulation and gene expression (5-7); and 3) poly-(ADP-ribosyl)ation and resulting inhibition of the glycolytic enzyme glyceraldehyde 3-phosphate dehydrogenase, with concomitant activation of several major pathogenetic mechanisms, i.e., nonenzymatic glycation, protein kinase C, and hexosamine pathway (2). Using a pharmacological approach with several structurally unrelated PARP inhibitors as well as PARP-deficient mice, we have recently discovered the key role of PARP in the development of early peripheral diabetic neuropathy (PDN) (3,8). Note that PARP inhibitors administered in doses resulting in complete or almost complete PARP inhibition in the diabetic peripheral nerve (3,8) appeared at least 100-fold more effective in correcting nerve conduction slowing, NAD ϩ /NADH redox imbalances, energy failure, and neurovascular dysfunction than conventional antioxidants (9,10).A recent 9-month PARP inhibitor study in the streptozotocin (STZ)-induced diabetic rat model did not reveal clearly manifest side effects (4), and PARP Ϫ/Ϫ mice do not develop obvious phenotypic changes (5). However, the long-term consequences of complete PARP inhibition in pathological conditions associated with oxidative stress, including diabetes, are unclear and can hardly be sorted out in rodents because of their limited life span. Diabetesassociated oxidative stress leads to DNA damage, e.g., in the peripheral nervous system (11), and PARP activation is an important mechanism of DNA repair (5). Therefore, it is reasonable to suggest that 1) complete PARP inhibition can potentially result in premature aging and 2) targeted delivery of PARP-1 antisense oligodeoxynucleotide-containing vectors (12) or PARP-1 RNA interference (RNAi) (13), rather than pharmacological PARP inhibition, should be considered as a future therapy of PDN (1). However, it is unlikely that such approaches will be available in clinical practice in the near future. An alternative strategy would be to develop low-dose PARP inhibitor-containing combination therapies with other agents already used in clinical practice and proven to be effective in the treatment

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Section: Discussionmentioning

confidence: 99%

Low-Dose Poly(ADP-Ribose) Polymerase Inhibitor-Containing Combination Therapies Reverse Early Peripheral Diabetic Neuropathy

Drel

Szabó

et al. 2005

Diabetes

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“…Like in the case of KYN, recent studies describe the implication of AGEs in the pathogenesis of diabetes complications and implicitly, neuropathy [14,15]. Peripheral nerves represent one of the favorite sites of AGEs both in the case of human subjects and experimental diabetes in animals [16]. The presence of carboxymethyllisine, one of the products belonging to this large class of AGEs, was described in vascular endothelial cells, pericytes, basement membrane, as well as in axons and Schwann cells belonging to peripheral nerve tissue [17].…”

Section: Resultsmentioning

confidence: 99%

The Assessment of Fluorophores Advanced Glycation End Products-to-Kynurenine Ratio in Healthy and Diabetic Rats and Humans

Olar¹,

Ciobanu²,

Matei³

et al. 2018

Studia UBB Chemia

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In this study, we calculated the ratio of the serum contributions of two highly studied fluorophore products (advanced glycation end productsAGEs and kynurenine -KYN) in the area of nutrition and metabolic diseases including diabetes mellitus (DM), by using a non-invasive, economical and easy-to-perform method. Blood serum spectrofluorimetric analysis was performed both in the case of normoglycemic (n=10) and diabetic rats (n=10), and in the case of non-diabetic (n=14) and type 2 diabetes mellitus (T2DM) patients (n=52). Our results showed a significant increase in the contributions of the two products in diabetic patients and rats compared to the control group. The ratio of the two compounds was positively correlated with serum glucose levels in the case of rats, and with serum triglyceride values in the case of humans. Also, the presence of DM complications in human subjects and the subsequent calculation of ROC curves led to a predictive value of the investigated ratio (AGEs/KYN) for the presence of peripheral diabetic polyneuropathy (PNP). The obtained results suggest a high potential for the investigated ratio to be considered as a new biomarker for the presence of PNP.

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Section: Vascular Endothelial Growth Factor (Vegf)mentioning

confidence: 95%

“…However, it seems evident that therapies such as vitamins may not be the ideal antioxidant strategy in human DN. Vitamin B6 derivatives (Hammes, Du et al 2003;Endo, Nishiyama et al 2007), metformin (Rahbar, Natarajan et al 2000), OPB-9195 (Wada, Nishizawa et al 2001;Mizutani, Ikeda et al 2002), ACEi (Miyata, van Ypersele de Strihou et al 2002;Coughlan, Thallas-Bonke et al 2007), AT1 antagonists (Miyata, van Ypersele de Strihou et al 2002), ALA (Coughlan, Thallas-Bonke et al 2007) and sRAGE (Wautier, Zoukourian et al 1996) have exhibited beneficial effects on excess superoxide generation within tissues, associated with improvements in the development and/or progression of diabetic complications. Vitamin B-related therapeutics are effective scavengers of ROS intermediates.…”

Section: Reactive Oxygen Speciesmentioning

confidence: 99%

“…Recent findings, however, have demonstrated the importance of VEGF within the diabetic kidney (De Vriese, Tilton et al 2001;Wada, Nishizawa et al 2001;Rizkalla, Forbes et al 2003;Thallas-Bonke, Lindschau et al 2004)]. We and others have previously shown both in vivo and in vitro decreases in VEGF expression with a number of therapies including alagebrium (Thallas-Bonke, Lindschau et al 2004), ACE inhibitors (Thallas-Bonke, Lindschau et al 2004, sRAGE and OPB-9195 (Wada, Nishizawa et al 2001). Despite this suppression of VEGF as a result of current therapeutics, the benefits of VEGF suppression remain controversial with some studies suggesting that VEGF blockade is renoprotective (De Vriese, Tilton et al 2001), whereas recent studies, albeit in a non-diabetic context, suggest that VEGF is a critical renal survival factor and that blockade may in fact promote renal damage (Advani, Kelly et al 2007).…”

Section: Vascular Endothelial Growth Factor (Vegf)mentioning

confidence: 99%

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Diabetic Nephropathy: Current and Novel Therapeutic Approaches to Prevent Its Development and Progression

Sourris¹,

Forbes²

2012

Diseases of Renal Parenchyma

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Effects of OPB‐9195, anti‐glycation agent, on experimental diabetic neuropathy

Abstract: The current study suggested that OPB is beneficial for the reduction of serum AGE and the prevention of diabetic neuropathy.

Cited by 92 publications

References 46 publications

Low-Dose Poly(ADP-Ribose) Polymerase Inhibitor-Containing Combination Therapies Reverse Early Peripheral Diabetic Neuropathy

Low-Dose Poly(ADP-Ribose) Polymerase Inhibitor-Containing Combination Therapies Reverse Early Peripheral Diabetic Neuropathy

The Assessment of Fluorophores Advanced Glycation End Products-to-Kynurenine Ratio in Healthy and Diabetic Rats and Humans

Diabetic Nephropathy: Current and Novel Therapeutic Approaches to Prevent Its Development and Progression

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