Effect of α-lipoic acid on vascular responses and nociception in diabetic rats

Cameron, Norman E.; Jack, Alison Margaret; Cotter, Mary A.

doi:10.1016/s0891-5849(01)00564-0

Cited by 84 publications

(72 citation statements)

References 67 publications

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“…Numerous pharmacological studies in animal models have been performed to sort out the involvement of the key hyperglycemia-induced biochemical mechanisms in diabetesassociated changes in thermal nociception. Aldose reductase inhibitors (ARIs, Calcutt et al, 2004), antioxidants i.e., taurine (Li et al, 2005b), α-lipoic acid (Cameron et al, 2001a), the hydroxyl radical scavenger dimethylthiourea (Cameron et al, 2001b), as well as the protein kinase C inhibitor LY333531 (Cotter et al, 2002), the PARP inhibitor 1,5-isoqunolinediol and PARP inhibitor-containing combination therapies (Li et al, 2005a), have been found to prevent or correct thermal hyperalgesia in STZ-diabetic rats. Taurine prevented thermal hyperalgesia in ZDF rats (Li et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

“…Another phenomenon, mechanical hyperalgesia, detected by reduced paw withdrawal thresholds during paw stimulation with rigid von Frey filaments or Randall-Sellito test, has been found clearly manifest in STZ-diabetic and ZDF rats (Cameron et al, 2001a,b;Cotter et al, 2002;Ilnytska et al, 2006;Li et al, 2006), and reversed or alleviated by antioxidants including α-lipoic acid (Cameron et al, 2001a), dimethylthiourea (Cameron et al, 2001b), taurine (Li et al, 2005b) as well as PARP inhibitors . Of interest, STZdiabetic mice develop mechanical hypo-, rather than hyperalgesia, i.e.…”

Section: Discussionmentioning

confidence: 99%

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A peroxynitrite decomposition catalyst counteracts sensory neuropathy in streptozotocin-diabetic mice

Drel

Pacher

Vareniuk

et al. 2007

European Journal of Pharmacology

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Whereas an important role of free radicals and oxidants in peripheral diabetic neuropathy is well established, the contribution of nitrosative stress and, in particular, of the highly reactive oxidant peroxynitrite, has not been properly explored. Our previous findings implicate peroxynitrite in diabetes-associated motor and sensory nerve conduction deficits and peripheral nerve energy deficiency and poly(ADP-ribose) polymerase activation associated with Type 1 diabetes. In this study the role of nitrosative stress in diabetic sensory neuropathy is evaluated. The peroxynitrite decomposition catalyst Fe(III) tetrakis-2-(N-triethylene glycol monomethyl ether)pyridyl porphyrin (FP15) was administered to control and streptozotocin (STZ)-diabetic mice at the dose of 5 mg kg −1 day −1 (FP15), for 3 weeks after initial 3 weeks without treatment. Mice with 6-week duration of diabetes developed clearly manifest thermal hypoalgesia (paw withdrawal, tail-flick, and hot plate tests), mechanical hypoalgesia (tail pressure Randall-Sellito test), tactile allodynia (flexible von Frey filament test), and ~38% loss of intraepidermal nerve fibers. They also had increased nitrotyrosine and poly(ADP-ribose) immunofluorescence in the sciatic nerve, grey matter of spinal cord, and dorsal root ganglion neurons. FP15 treatment was associated with alleviation of thermal and mechanical hypoalgesia. Tactile response threshold tended to increase in response to peroxynitrite decomposition catalyst treatment, but still remained ~59% lower compared with non-diabetic controls. Intraepidermal nerve fiber density was 25% higher in FP15-treated than in untreated diabetic rats, but the difference between two groups did not achieve statistical significance (p=0.054). Nitrotyrosine and poly(ADP-ribose) immunofluorescence in sciatic nerve, spinal cord, and dorsal root ganglion neurons of peroxynitrite decomposition catalyst-treated diabetic mice were markedly reduced. In conclusion, nitrosative stress plays an important role in sensory neuropathy associated with Type 1 diabetes. The findings provide rationale for further studies of peroxynitrite decomposition catalysts in a long-term diabetic model. KeywordsIntraepidermal nerve fiber loss; Nitrosative stress; Peroxynitrite decomposition catalyst; Poly(ADPribose) polymerase; Tactile allodynia; Thermal hypoalgesia Evidence for important role of the potent oxidant peroxynitrite, a product of superoxide anion radicals with nitric oxide, in the pathogenesis of diabetes (Olcott et al., 2004;Szabo et al., 2002a;Pacher et al., 2007) and diabetic complications (Nangle et al., 2004;Obrosova et al., 2005b;Pacher et al., 2005;Pacher et al., 2007;Szabo et al., 2002a) is emerging. Accumulation of nitrotyrosine [NT, a footprint of peroxynitrite-and other reactive nitrogen species (RNS)-induced protein nitration] has been documented in vascular endothelium (Pacher et al., 2005;Szabo et al., 2002b), myocardium (Pacher et al., 2005), retina (Cheung et al., 2005;Obrosova et al., 2005c), and kidneys (Drel et al.,...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A peroxynitrite decomposition catalyst counteracts sensory neuropathy in streptozotocin-diabetic mice

Drel

Pacher

Vareniuk

et al. 2007

European Journal of Pharmacology

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“…17,18 Thus, studies of mechanisms underlying both thermal hyperalgesia and thermal hypoalgesia and the development of agents to prevent and treat both disorders are clinically relevant. Thermal hyperalgesia has been described in streptozotocin (STZ)-diabetic and Zucker diabetic fatty rats with short-term (2-8 weeks) diabetes, [19][20][21][22] as well as in type 1 insulinopenic BB/Wor and type 2 hyperinsulinemic diabetic BBZDR/Wor rats. 23,24 This phenomenon develops with participation of multiple pathogenetic mechanisms, including (but not limited to) increased aldose reductase (AR), 19 the advanced glycation end product/receptor for advanced glycation end product (AGE/RAGE) axis, 25 protein kinase C (PKC), 26 poly(ADP-ribose) polymerase (PARP), 12 and angiotensin converting enzyme (ACE) activities, 22 oxidative stress, 20,21 and C-peptide deficiency.…”

Section: Pathogenesis and Experimental Treatments Of Diabetes-associamentioning

confidence: 99%

“…23,24 This phenomenon develops with participation of multiple pathogenetic mechanisms, including (but not limited to) increased aldose reductase (AR), 19 the advanced glycation end product/receptor for advanced glycation end product (AGE/RAGE) axis, 25 protein kinase C (PKC), 26 poly(ADP-ribose) polymerase (PARP), 12 and angiotensin converting enzyme (ACE) activities, 22 oxidative stress, 20,21 and C-peptide deficiency. 27 Thermal hyperalgesia in STZ-diabetic rats was prevented or reversed by the AR inhibitor lidorestat, 19 the AGE formation inhibitor pyridoxamine, 25 the PKC LY333531, 26 several antioxidants (including ␣-lipoic acid, 20 the hydroxyl radical scavenger dimethylthiourea, 21 the xanthine oxidase inhibitor allopurinol, 28 and taurine 29 ), the PARP inhibitors 1,5-isoquinolinediol 12 and nicotinamide, 30 and the neurocytokine interleukin-6, 31 as well as by transgene-mediated expression of enkephalin in dorsal root ganglia neurons. 32 C-peptide and the glutamate carboxypeptidase II inhibitor treatments alleviated thermal hyperalgesia in type 1 diabetic BB/ Wor rats, 27,33 and taurine in type 2 Zucker diabetic fatty rats.…”

Section: Pathogenesis and Experimental Treatments Of Diabetes-associamentioning

confidence: 99%

“…In experimental studies, mechanical withdrawal thresholds in diabetic rat and mouse models are assessed by paw (rats) and tail (mouse) pressure Randall-Selitto test or with a von Frey aesthesiometer and rigid von Frey filaments. Mechanical hyperalgesia has been reported in both STZ-diabetic 20,21,30,77,78 and Zucker diabetic fatty rats, 34,79 in which pressure pain preceded development of type 2 diabetes. In contrast, STZ-diabetic C57Bl/6J mice 13,14,46,47 displayed elevated mechanical withdrawal thresholds.…”

Section: Pathogenesis and Experimental Treatments: Diabetes-associatementioning

confidence: 99%

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Diabetic Painful and Insensate Neuropathy: Pathogenesis and Potential Treatments

2009

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Summary:Advanced peripheral diabetic neuropathy (PDN) is associated with elevated vibration and thermal perception thresholds that progress to sensory loss and degeneration of all fiber types in peripheral nerve. A considerable proportion of diabetic patients also describe abnormal sensations such as paresthesias, allodynia, hyperalgesia, and spontaneous pain. One or several manifestations of abnormal sensation and pain are described in all the diabetic rat and mouse models studied so far (i.e., streptozotocin-diabetic rats and mice, type 1 insulinopenic BB/Wor and type 2 hyperinsulinemic diabetic BBZDR/Wor rats, Zucker diabetic fatty rats, and nonobese diabetic, Akita, leptin-and leptin-receptor-deficient, and highfat diet-fed mice). Such manifestations are 1) thermal hyperalgesia, an equivalent of a clinical phenomenon described in early PDN; 2) thermal hypoalgesia, typically present in advanced PDN; 3) mechanical hyperalgesia, an equivalent of pain on pressure in early PDN; 4) mechanical hypoalgesia, an equivalent to the loss of sensitivity to mechanical noxious stimuli in advanced PDN; 5) tactile allodynia, a painful perception of a light touch; and 5) formalin-induced hyperalgesia. Rats with short-term diabetes develop painful neuropathy, whereas those with longer-term diabetes and diabetic mice typically display manifestations of both painful and insensate neuropathy, or insensate neuropathy only. Animal studies using pharmacological and genetic approaches revealed important roles of increased aldose reductase, protein kinase C, and poly(ADPribose) polymerase activities, advanced glycation end-products and their receptors, oxidative-nitrosative stress, growth factor imbalances, and C-peptide deficiency in both painful and insensate neuropathy. This review describes recent achievements in studying the pathogenesis of diabetic neuropathic pain and sensory disorders in diabetic animal models and developing potential pathogenetic treatments. Key Words: Animal models, diabetic insensate neuropathy, diabetic painful neuropathy, formalin-induced hyperalgesia, mechanical hyper-and hypoalgesia, pathogenetic treatments of diabetic neuropathic pain and sensory loss, symptomatic treatments of diabetic pain, tactile allodynia, thermal hyper-and hypoalgesia.

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Antiallodynic interaction and motor performance of the pregabalin/thioctic acid and pregabalin/α‐tocopherol combinations in neonatal streptozotocin‐induced diabetic rats

Cruz-Álvarez

Zúñiga-Romero

Huerta-Cruz

et al. 2018

Drug Development Research

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Painful peripheral neuropathy can be associated with nerve damage caused by diabetes mellitus. Although pregabalin is the first‐line therapy for peripheral neuropathy, it shows substantial discontinuation rates, mainly because of nervous system side effects as motor incoordination. Multimodal therapy may improve the motor side effect profile of pregabalin. The aim of this study was to evaluate the interaction of pregabalin + thioctic acid or pregabalin + α‐tocopherol on allodynia and motor performance in neonatal streptozotocin‐induced diabetic rats. Efficacy of drugs separately or in combination was tested by tactile allodynia using von Frey filaments. Isobolographic and interaction index analysis were used to determine the antiallodynic interaction between pregabalin and either thioctic acid or α‐tocopherol. Motor performance was measured using a rotarod test. Pregabalin, thioctic acid, and α‐tocopherol reduced, in a dose‐dependent fashion, tactile allodynia. Pregabalin + thioctic acid and pregabalin + α‐tocopherol combinations also dose‐dependently reduced allodynic behavior in diabetic rats. Isobolographic analysis revealed an additive interaction for both combinations. Consistently, the interaction indices confirmed the additive effect between pregabalin + thioctic acid and pregabalin + α‐tocopherol. In addition, the administration of either combination improved motor incoordination induced by pregabalin. Data suggests that thioctic acid or α‐tocopherol could positively impact the therapeutic profile of pregabalin, because they might be useful for reducing motor incoordination associated to pregabalin in patients with peripheral neuropathy.

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Effect of α-lipoic acid on vascular responses and nociception in diabetic rats

Cited by 84 publications

References 67 publications

A peroxynitrite decomposition catalyst counteracts sensory neuropathy in streptozotocin-diabetic mice

A peroxynitrite decomposition catalyst counteracts sensory neuropathy in streptozotocin-diabetic mice

Diabetic Painful and Insensate Neuropathy: Pathogenesis and Potential Treatments

Antiallodynic interaction and motor performance of the pregabalin/thioctic acid and pregabalin/α‐tocopherol combinations in neonatal streptozotocin‐induced diabetic rats

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