scholarly journals Effect of Dietary Content of Menhaden Oil with or without Salsalate on Neuropathic Endpoints in High-Fat-Fed/Low-Dose Streptozotocin-Treated Sprague Dawley Rats

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Eric P. Davidson ◽  
Lawrence J. Coppey ◽  
Hanna Shevalye ◽  
Alexander Obrosov ◽  
Mark A. Yorek
Keyword(s):  
Vascular Reactivity ◽  
Sensory Nerve ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Neural Function ◽  
Menhaden Oil ◽  
High Fat ◽  
Fiber Density ◽  
Thermal Nociception ◽  
Intraepidermal Nerve Fiber Density

In this study, we wanted to extend our investigation of the efficacy of fish oil with or without salsalate on vascular and neural complications using a type 2 diabetic rat model. Four weeks after the onset of hyperglycemia, diabetic rats were treated via the diet with 3 different amounts of menhaden oil with or without salsalate for 12 weeks. Afterwards, vascular reactivity of epineurial arterioles and neuropathy-related endpoints were examined. The addition of salsalate to high-fat diets enriched with 10% or 25% kcal of menhaden oil protected vascular reactivity to acetylcholine and calcium gene-related peptide, motor and sensory nerve conduction velocity, thermal nociception, intraepidermal nerve fiber density, and cornea sensitivity to a greater extent than 10% or 25% menhaden oil alone. Vascular and neural function was maximally protected with diet containing 45% kcal as menhaden oil, and adding salsalate did not provide any additional benefit. Salsalate alone in the high-fat diet of diabetic rats provided minimal protection/improvement of vascular and neural dysfunction. These studies imply that dietary salsalate in combination with lower amounts of menhaden oil can provide greater benefit toward diabetes-induced vascular and neural impairment than menhaden oil alone.

scholarly journals Effect of Inhibition of Angiotensin-Converting Enzyme and/or Neutral Endopeptidase on Neuropathy in High-Fat-Fed C57Bl/6J Mice

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Lawrence Coppey ◽  
Bao Lu ◽  
Craig Gerard ◽  
Mark A. Yorek
Keyword(s):  
Nerve Conduction Velocity ◽  
Sensory Nerve ◽  
Neutral Endopeptidase ◽  
Neural Function ◽  
Fiber Density ◽  
Thermal Nociception ◽  
Intraepidermal Nerve Fiber Density ◽  
Deficient Mice ◽  
Nerve Fiber Density ◽  
Intraepidermal Nerve Fiber

We have demonstrated that treating diet-induced obese (DIO) mice with the vasopeptidase inhibitor ilepatril improved neural function. Vasopeptidase inhibitors block angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP) activity. We propose that increased activity of ACE and NEP contributes to pathophysiology of DIO. To address this issue C57Bl/6J mice or mice deficient in NEP were fed a high-fat diet and treated with ilepatril, enalapril, ACE inhibitor, or candoxatril, NEP inhibitor, using both prevention and intervention protocols. Endpoints included glucose utilization and neural function determination. In the prevention study glucose tolerance was impaired in DIO C57Bl/6J mice and improved with ilepatril or enalapril. Sensory nerve conduction velocity, thermal nociception, and intraepidermal nerve fiber density were impaired in DIO C57Bl/6J mice and improved with ilepatril or candoxatril. In the intervention study only enalapril improved glucose tolerance. Sensory nerve conduction velocity and intraepidermal nerve fiber density were improved by all three treatments, whereas thermal nociception was improved by ilepatril or candoxatril. In NEP-deficient mice DIO impaired glucose utilization and this was improved with enalapril. Nerve function was not impaired by DIO in NEP-deficient mice. These studies suggest that ACE and NEP play a role in pathophysiology associated with DIO.

Treatment with Actovegin® Improves Sensory Nerve Function and Pathology in Streptozotocin-Diabetic Rats via Mechanisms Involving Inhibition of PARP Activation

2011 ◽  
Vol 120 (03) ◽  
pp. 132-138 ◽  
Author(s):  
A. Dieckmann ◽  
M. Kriebel ◽  
E. Andriambeloson ◽  
D. Ziegler ◽  
M. Elmlinger
Keyword(s):  
Diabetic Neuropathy ◽  
Nerve Conduction Velocity ◽  
Sensory Nerve ◽  
Diabetic Rats ◽  
Sensory Nerve Conduction Velocity ◽  
Fiber Density ◽  
Parp Activation ◽  
Intraepidermal Nerve Fiber Density ◽  
Nerve Fiber Density ◽  
Intraepidermal Nerve Fiber

AbstractDiabetic neuropathy is one of the most severe complications of diabetes, affecting approximately one-third of diabetic patients. We investigated the potential neuroprotective effect of Actovegin®, a deproteinized hemoderivative of calf blood, in an animal model of diabetic neuropathy.A single intravenous injection of streptozotocin (STZ, 55 mg/kg) was used to induce experimental diabetes in male Sprague-Dawley rats. Actovegin® (200 or 600 mg/kg) was administered intraperitoneally from day 11 to day 40 post-STZ exposure. N-acetylcysteine (NAC) was used as a positive control and was added to drinking water (0.2 g/l) from day 2 until day 40. Measurements to assess efficacy included sensory nerve conduction velocity (SNCV), intraepidermal nerve fiber density (IENFD), and poly(ADP-ribose) content.A decrease (35%) in sensory nerve conduction velocity (SNCV) was seen in STZ-induced diabetic rats from day 10 post-STZ administration and persisted at days 25 and 39. At study completion (day 41), a decrease (32%) in intraepidermal nerve fiber density (IENFD) was found in hind-paw skin biopsies from STZ-rats. Reduced SNCV and IENFD were significantly ameliorated by both doses of Actovegin®. More­over, 600 mg/kg Actovegin® markedly decreased poly(ADP-ribose) polymerase (PARP) activity in sciatic nerves from STZ-diabetic rats as assessed by poly(ADP-ribose) content.Actovegin® improved several para­meters of experimental diabetic neuropathy via mechanisms involving suppression of PARP activation, providing a rationale for treatment of this disease in humans.

scholarly journals Effect of High-Fat Diet on Peripheral Neuropathy in C57BL/6 Mice

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Lingling Xu ◽  
Dou Tang ◽  
Meiping Guan ◽  
Cuihua Xie ◽  
Yaoming Xue
Keyword(s):  
Oxidative Stress ◽  
Peripheral Neuropathy ◽  
Nerve Fiber ◽  
High Fat Diet ◽  
Sensory Nerve ◽  
Thermal Hyperalgesia ◽  
High Fat ◽  
Fiber Density ◽  
Dendrite Length ◽  
Intraepidermal Nerve Fiber Density

Objective. Dyslipidemia may contribute to the development of peripheral neuropathy, even in prediabetics; however, few studies have evaluated vascular dysfunction and oxidative stress in patients with peripheral neuropathy.Methods. Using high-fat diet- (HFD-) induced prediabetic C57BL/6 mice, we assessed motor and sensory nerve conduction velocity (NCV) using a BIOPAC System and thermal algesia with a Plantar Test (Hargreaves’ method) Analgesia Meter. Intraepidermal nerve fiber density and mean dendrite length were tested following standard protocols. Vascular endothelial growth factor-A (VEGF-A) and 12/15-lipoxygenase (12/15-LOX) were evaluated by immunohistochemistry and Western blot, respectively.Results. HFD-fed mice showed deficits in motor and sensory NCV, thermal hyperalgesia, reduced mean dendrite length, and VEGF-A expression in the plantar skin and increased 12/15-LOX in the sciatic nerve (P<0.05compared with controls).Conclusion. HFD may cause large myelinated nerve and small sensory nerve fiber damage, thus leading to neuropathy. The mean dendrite length may be a more sensitive marker for early detection of peripheral neuropathy. Reduced blood supply to the nerves and increased oxidative stress may contribute to the development and severity of peripheral neuropathy.

scholarly journals Treatment of Streptozotocin-Induced Diabetic Rats with Alogliptin: Effect on Vascular and Neural Complications

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Eric P. Davidson ◽  
Lawrence J. Coppey ◽  
Brian Dake ◽  
Mark A. Yorek
Keyword(s):  
Conduction Velocity ◽  
Nerve Conduction ◽  
Nerve Conduction Velocity ◽  
Sensory Nerve ◽  
Diabetic Rats ◽  
Fiber Density ◽  
Dpp Iv ◽  
Intraepidermal Nerve Fiber Density ◽  
Calcitonin Gene ◽  
Nerve Fiber Density

We sought to determine the effect of dipeptidyl peptidase IV (DPP-IV) inhibition on streptozotocin diabetes-induced vascular and neural dysfunction. After 4 weeks of untreated diabetes, rats were treated for 12 weeks with Alogliptin (DPP-IV inhibitor). Diabetes caused a slowing of motor and sensory nerve conduction velocity, thermal hypoalgesia, reduction in intraepidermal nerve fiber density in the hindpaw, and impairment in vascular relaxation to acetylcholine and calcitonin gene-related peptide in epineurial arterioles. Treatment significantly improved motor nerve conduction velocity and thermal response latency. Sensory nerve conduction velocity was marginally improved with treatment of diabetic rats, and treatment did not improve the decrease in intraepidermal nerve fiber density. Vascular relaxation by epineurial arterioles to calcitonin gene-related peptide but not acetylcholine was significantly improved with treatment. These studies suggest that some but not all vascular and neural complications associated with type 1 diabetes can be improved with the inhibition of DPP-IV activity.

scholarly journals Partial Replacement with Menhaden Oil Improves Peripheral Neuropathy in High-Fat-Fed Low-Dose Streptozotocin Type 2 Diabetic Rat

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Lawrence J. Coppey ◽  
Amey Holmes ◽  
Eric P. Davidson ◽  
Mark A. Yorek
Keyword(s):  
Diabetic Neuropathy ◽  
High Fat Diet ◽  
Serum Lipid ◽  
Low Dose ◽  
Sensory Nerve ◽  
Diabetic Rats ◽  
Partial Replacement ◽  
Menhaden Oil ◽  
High Fat

Aims. To determine the effect of partial replacement of a high-fat diet with menhaden oil on diabetic neuropathy in an animal model of type 2 diabetes.Materials and Methods. High-fat/low-dose streptozotocin diabetic rats were used to examine the influence of replacing 50% of the source of the high-fat diet (lard) with menhaden oil, a natural source of n-3 fatty acids, on diabetic neuropathy. Endpoints included analyses of glucose tolerance, fatty liver disease, serum and liver fatty acid composition, serum lipid and adiponectin levels, motor and sensory nerve conduction velocity, thermal sensitivity and innervation of the hindpaw.Results. Diabetic rats were insulin resistant and menhaden oil did not improve whole animal glucose utilization. Menhaden oil did not improve elevated HbA1C levels or serum lipid levels but serum levels of adiponectin were significantly increased and hepatic steatosis was significantly improved. Diabetic rats were thermal hypoalgesic, had reduced motor and sensory nerve conduction velocities and intraepidermal nerve fiber profiles were decreased in the hindpaw and these endpoints were significantly improved with menhaden oil.Conclusions. We found that enrichment of a high-fat diet with menhaden oil improved a number of endpoints associated with diabetic neuropathy.

scholarly journals Modification of vasodilator response in streptozotocin-induced diabetic rat

1999 ◽  
Vol 77 (12) ◽  
pp. 980-985 ◽  
Author(s):  
Jean-François Bouchard ◽  
Éric C Dumont ◽  
Daniel Lamontagne
Keyword(s):  
Diabetes Mellitus ◽  
Adenylyl Cyclase ◽  
Dose Response ◽  
Vascular Reactivity ◽  
Diabetic Rats ◽  
Diabetic Rat ◽  
Response Curves ◽  
Experimental Conditions ◽  
Isolated Hearts ◽  
Dose Response Curves

Functional dilatory response in streptozotocin-induced diabetic rats was investigated using thoracic aortas, isolated hearts, and mesenteric beds. Dose-response curves to the PGI2 analogue iloprost on phenylephrine-preconstricted rings of diabetic rats and controls were comparable. In contrast, decreased vasodilation in diabetic rats was observed when dose-response curves to iloprost were performed in hearts and on phenylephrine-preconstricted mesenteric beds. Dose-response curves to forskolin, an adenylyl cyclase activator, performed with hearts and phenylephrine-preconstricted aortic rings and isolated mesenteric beds of diabetic rats and controls were comparable. However, a decreased vasodilation to the ATP-sensitive potassium channel (KATP) activator lemakalim was observed in diabetic hearts, but not in aortic rings and mesenteric beds. In conclusion, under our experimental conditions, diabetes mellitus affects the vasodilation to iloprost in both coronary and mesenteric beds, but not in the aorta. In the heart, this modification of vascular reactivity may be due to a decrease in KATP channel mediated response and not to a decreased activity of adenylyl cyclase. At this time, in the isolated mesenteric bed, the mechanism of this modification in vascular reactivity remains unknown.Key words: diabetes mellitus, iloprost, KATP channels, adenylyl cyclase, aorta, coronary circulation, mesenteric bed.

scholarly journals Cold Exposure Exacerbates the Development of Diabetic Polyneuropathy in the Rat

2009 ◽  
Vol 2009 ◽  
pp. 1-9 ◽  
Author(s):  
Lora J. Kasselman ◽  
Aristidis Veves ◽  
Christopher H. Gibbons ◽  
Seward B. Rutkove
Keyword(s):  
Cold Exposure ◽  
Room Temperature ◽  
Sensory Nerve ◽  
Diabetic Polyneuropathy ◽  
Diabetic Rats ◽  
Nerve Fibers ◽  
H Reflex ◽  
Cold Environment ◽  
Fiber Density ◽  
The Relationship

Diabetic polyneuropathy (DPN) and cold-induced nerve injury share several pathogenic mechanisms. This study explores whether cold exposure contributes to the development of DPN. Streptozotocin-induced diabetic rats and controls were exposed to a room temperature (23∘C) or cold environment (10∘C). H-reflex, tail and sciatic motor, and sensory nerve conduction studies were performed. Analyses of sural nerve, intraepidermal nerve fibers, and skin and nerve nitrotyrosine ELISAs were performed. Diabetic animals exposed to a cold environment had an increased H-reflex four weeks earlier than diabetic room temperature animals (P=.03). Cold-exposed diabetic animals also had greater reduction in motor conduction velocities at 20 weeks (P=.017), decreased skin nerve fiber density (P=.037), and increased skin nitrotyrosine levels (P=.047). Cold exposure appears to hasten the development of DPN in the rat STZ model of diabetes. These findings support that further study into the relationship between ambient temperature and DPN is warranted.

Early skin denervation in hereditary and iatrogenic transthyretin amyloid neuropathy

Neurology ◽  
2017 ◽  
Vol 88 (23) ◽  
pp. 2192-2197 ◽  
Author(s):  
Teruaki Masuda ◽  
Mitsuharu Ueda ◽  
Genki Suenaga ◽  
Yohei Misumi ◽  
Masayoshi Tasaki ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Detection Threshold ◽  
Sensory Nerve ◽  
Clinical Score ◽  
Clinical Findings ◽  
Fiber Density ◽  
Mutation Carriers ◽  
Presymptomatic Stage ◽  
Intraepidermal Nerve Fiber Density ◽  
V30m Mutation

Objective:To elucidate early skin denervation in hereditary transthyretin (TTR) amyloidosis and iatrogenic TTR amyloidosis.Methods:We investigated intraepidermal nerve fiber density (IENFD) and clinical findings in 32 patients with hereditary TTR amyloidosis, 11 asymptomatic mutation carriers, 6 patients with iatrogenic TTR amyloidosis, and 23 healthy volunteers.Results:IENFD values were reduced in patients with the V30M mutation (1.9 ± 2.1 per 1 mm), patients with non-V30M mutations (5.8 ± 3.2 per 1 mm), and patients with iatrogenic TTR amyloidosis (3.5 ± 1.8 per 1 mm) compared with healthy volunteers (11.8 ± 3.2 per 1 mm) (p < 0.01). Skin denervation also occurred, even in presymptomatic V30M mutation carriers (5.0 ± 2.2 per 1 mm). The IENFD was correlated with disease duration (ρ = −0.533, p = 0.002) and various peripheral neuropathy parameters such as sensory impairment in the Kumamoto clinical score (ρ = −0.575, p = 0.001), heat-pain detection threshold (ρ = −0.704, p < 0.001), and sural sensory nerve action potential (ρ = 0.481, p = 0.005). TTR amyloid deposits frequently occurred in connective tissues and vessels of the dermal reticular layer in patients with hereditary TTR amyloidosis and those with iatrogenic TTR amyloidosis.Conclusions:Patients with hereditary TTR amyloidosis and those with iatrogenic TTR amyloidosis may show early skin denervation even in the presymptomatic stage. IENFD may thus be useful for early diagnosis and may serve as a biomarker in clinical trials for hereditary and iatrogenic TTR amyloidosis.

scholarly journals Anti-diabetic activity of chromium picolinate and biotin in rats with type 2 diabetes induced by high-fat diet and streptozotocin

2012 ◽  
Vol 110 (2) ◽  
pp. 197-205 ◽  
Author(s):  
Kazim Sahin ◽  
Mehmet Tuzcu ◽  
Cemal Orhan ◽  
Nurhan Sahin ◽  
Osman Kucuk ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Serum Insulin ◽  
Diabetic Rats ◽  
Chromium Picolinate ◽  
Diabetic Rat ◽  
High Fat ◽  
Regular Diet ◽  
Ppar Γ ◽  
Type 2 Diabetic

The objective of the present study was to evaluate anti-diabetic effects of chromium picolinate (CrPic) and biotin supplementations in type 2 diabetic rats. The type 2 diabetic rat model was induced by high-fat diet (HFD) and low-dose streptozotocin. The rats were divided into five groups as follows: (1) non-diabetic rats fed a regular diet; (2) diabetic rats fed a HFD; (3) diabetic rats fed a HFD and supplemented with CrPic (80 μg/kg body weight (BW) per d); (4) diabetic rats fed a HFD and supplemented with biotin (300 μg/kg BW per d); (5) diabetic rats fed a HFD and supplemented with both CrPic and biotin. Circulating glucose, cortisol, total cholesterol, TAG, NEFA and malondialdehyde concentrations decreased (P< 0·05), but serum insulin concentrations increased (P< 0·05) in diabetic rats treated with biotin and CrPic, particularly with a combination of the supplements. Feeding a HFD to diabetic rats decreased PPAR-γ expression in adipose tissue and phosphorylated insulin receptor substrate 1 (p-IRS-1) expression of liver, kidney and muscle tissues, while the supplements increased (P< 0·001) PPAR-γ and p-IRS-1 expressions in relevant tissues. Expression of NF-κB in the liver and kidney was greater in diabetic rats fed a HFD, as compared with rats fed a regular diet (P< 0·01). The supplements decreased the expression of NF-κB in diabetic rats (P< 0·05). Results of the present study revealed that supplementing CrPic and biotin alone or in a combination exerts anti-diabetic activities, probably through modulation of PPAR-γ, IRS-1 and NF-κB proteins.

scholarly journals Enriching the diet with menhaden oil improves peripheral neuropathy in streptozotocin-induced type 1 diabetic rats

2015 ◽  
Vol 113 (3) ◽  
pp. 701-708 ◽  
Author(s):  
Lawrence J. Coppey ◽  
Eric P. Davidson ◽  
Alexander Obrosov ◽  
Mark A. Yorek
Keyword(s):  
Fatty Acids ◽  
Diabetic Neuropathy ◽  
Nerve Conduction ◽  
Sensory Nerve ◽  
Diabetic Rats ◽  
Menhaden Oil ◽  
Beneficial Effects ◽  
Intervention Protocol ◽  
Good Treatment Strategy

The purpose of this study was to determine the effect of supplementing the diet of type 1 diabetic rats with menhaden oil on diabetic neuropathy. Menhaden oil is a natural source for n-3 fatty acids, which have been shown to have beneficial effects in cardiovascular disease and other morbidities. Streptozotocin-induced diabetic rats were used to examine the influence of supplementing their diet with 25% menhaden oil on diabetic neuropathy. Both prevention and intervention protocols were used. Endpoints included motor and sensory nerve conduction velocity, thermal and mechanical sensitivity, and innervation and sensitivity of the cornea and hindpaw. Diabetic neuropathy as evaluated by the stated endpoints was found to be progressive. Menhaden oil did not improve elevated HbA1C levels or serum lipid levels. Diabetic rats at 16-wk duration were thermal hypoalgesic and had reduced motor and sensory nerve conduction velocities, and innervation and sensitivity of the cornea and skin were impaired. These endpoints were significantly improved with menhaden oil treatment following the prevention or intervention protocol. We found that supplementing the diet of type 1 diabetic rats with menhaden oil improved a variety of endpoints associated with diabetic neuropathy. These results suggest that enriching the diet with n-3 fatty acids may be a good treatment strategy for diabetic neuropathy.

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