The Experts below are selected from a list of 258 Experts worldwide ranked by ideXlab platform
Mark A. Yorek - One of the best experts on this subject based on the ideXlab platform.
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Characterization of Mice Ubiquitously Overexpressing Human 15-Lipoxygenase-1: Effect of Diabetes on Peripheral Neuropathy and Treatment with Menhaden Oil
Journal of Diabetes Research, 2021Co-Authors: Lawrence Coppey, Hanna Shevalye, Alexander Obrosov, Eric Davidson, William Paradee, Mark A. YorekAbstract:To rigorously explore the role of omega-3 polyunsaturated fatty acids (PUFA) in the treatment of diabetic peripheral neuropathy (DPN), we have created a transgenic mouse utilizing a Cre-lox promoter to control overexpression of human 15-lipoxygenase-1 (15-LOX-1). In this study, we sought to determine the effect of treating type 2 diabetic wild-type mice and transgenic mice ubiquitously overexpressing 15-LOX-1 with Menhaden Oil on endpoints related to DPN. Wild-type and transgenic mice on a C57Bl/6J background were divided into three groups. Two of each of these groups were used to create a high-fat diet/streptozotocin model for type 2 diabetes. The remaining mice were control groups. Four weeks later, one set of diabetic mice from each group was treated with Menhaden Oil for twelve weeks and then evaluated using DPN-related endpoints. Studies were also performed using dorsal root ganglion neurons isolated from wild-type and transgenic mice. Wild-type and transgenic diabetic mice developed DPN as determined by slowing of nerve conduction velocity, decreased sensory nerve fibers in the skin and cornea, and impairment of thermal and mechanical sensitivity of the hindpaw compared to their respective control mice. Although not significant, there was a trend for the severity of these DPN-related deficits to be less in the diabetic transgenic mice compared to the diabetic wild-type mice. Treating diabetic wild-type and transgenic mice with Menhaden Oil improved the DPN-related endpoints with a trend for greater improvement or protection by Menhaden Oil observed in the diabetic transgenic mice. Treating dorsal root ganglion neurons with docosahexanoic acid but not eicosapentaenoic acid significantly increased neurite outgrowth with greater efficacy observed with neurons isolated from transgenic mice. Targeting pathways that will increase the production of the anti-inflammatory metabolites of omega-3 PUFA may be an efficacious approach to developing an effective treatment for DPN.
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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.
Journal of diabetes research, 2018Co-Authors: Eric P. Davidson, Lawrence J. Coppey, Hanna Shevalye, Alexander Obrosov, Mark A. YorekAbstract: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.
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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
Experimental Diabetes Research, 2018Co-Authors: Eric P. Davidson, Lawrence J. Coppey, Hanna Shevalye, Alexander Obrosov, Mark A. YorekAbstract: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.
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Impaired Corneal Sensation and Nerve Loss in a Type 2 Rat Model of Chronic Diabetes Is Reversible With Combination Therapy of Menhaden Oil, α-Lipoic Acid, and Enalapril.
Cornea, 2017Co-Authors: Eric P. Davidson, Lawrence J. Coppey, Hanna Shevalye, Alexander Obrosov, Randy H. Kardon, Mark A. YorekAbstract:Purpose:This study investigated the efficacy of monotherapy versus combination of Menhaden Oil, α-lipoic acid, and enalapril on corneal sensation and morphometry and other neuropathy-related endpoints in a rat model of type 2 diabetes.Methods:Male Sprague-Dawley rats (aged 12 weeks) were fed a high-
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effect of combination therapy consisting of enalapril α lipoic acid and Menhaden Oil on diabetic neuropathy in a high fat low dose streptozotocin treated rat
European Journal of Pharmacology, 2015Co-Authors: Eric P. Davidson, Lawrence J. Coppey, Mark A. Yorek, Amey HolmesAbstract:We have previously demonstrated that treating diabetic rats with enalapril, an angiotensin converting enzyme (ACE) inhibitor, α-lipoic acid, an antioxidant, or Menhaden Oil, a natural source of omega-3 fatty acids can partially improve diabetic peripheral neuropathy. In this study we sought to determine the efficacy of combining these three treatments on vascular and neural complications in a high fat fed low dose streptozotocin treated rat, a model of type 2 diabetes. Rats were fed a high fat diet for 8 weeks followed by a 30 mg/kg dose of streptozotocin. Eight weeks after the onset of hyperglycemia diabetic rats were treated with a combination of enalapril, α-lipoic acid and Menhaden Oil. Diabetic rats not receiving treatment were continued on the high fat diet. Glucose clearance was impaired in diabetic rats and significantly improved with treatment. Diabetes caused steatosis, elevated serum lipid levels, slowing of motor and sensory nerve conduction, thermal hypoalgesia, reduction in intraepidermal nerve fiber profiles, decrease in cornea sub-basal nerve fiber length and corneal sensitivity and impairment in vascular relaxation to acetylcholine and calcitonin gene-related peptide in epineurial arterioles of the sciatic nerve. Treating diabetic rats with the combination of enalapril, α-lipoic acid and Menhaden Oil reversed all these deficits to near control levels except for motor nerve conduction velocity which was also significantly improved compared to diabetic rats but remained significantly decreased compared to control rats. These studies suggest that a combination therapeutic approach may be most effective for treating vascular and neural complications of type 2 diabetes.
Lawrence J. Coppey - One of the best experts on this subject based on the ideXlab platform.
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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.
Journal of diabetes research, 2018Co-Authors: Eric P. Davidson, Lawrence J. Coppey, Hanna Shevalye, Alexander Obrosov, Mark A. YorekAbstract: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.
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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
Experimental Diabetes Research, 2018Co-Authors: Eric P. Davidson, Lawrence J. Coppey, Hanna Shevalye, Alexander Obrosov, Mark A. YorekAbstract: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.
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Impaired Corneal Sensation and Nerve Loss in a Type 2 Rat Model of Chronic Diabetes Is Reversible With Combination Therapy of Menhaden Oil, α-Lipoic Acid, and Enalapril.
Cornea, 2017Co-Authors: Eric P. Davidson, Lawrence J. Coppey, Hanna Shevalye, Alexander Obrosov, Randy H. Kardon, Mark A. YorekAbstract:Purpose:This study investigated the efficacy of monotherapy versus combination of Menhaden Oil, α-lipoic acid, and enalapril on corneal sensation and morphometry and other neuropathy-related endpoints in a rat model of type 2 diabetes.Methods:Male Sprague-Dawley rats (aged 12 weeks) were fed a high-
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Effect of Treatment with Salsalate, Menhaden Oil, Combination of Salsalate and Menhaden Oil, or Resolvin D1 of C57Bl/6J Type 1 Diabetic Mouse on Neuropathic Endpoints.
Journal of nutrition and metabolism, 2016Co-Authors: Hanna Shevalye, Lawrence J. Coppey, Alexander Obrosov, Randy H. Kardon, Matthew S. YorekAbstract:Aims. In this study a streptozotocin induced type 1 diabetes mouse model was used to assess the effectiveness of salsalate, Menhaden Oil, the combination of salsalate and Menhaden Oil, or resolvin D1 on neuropathic endpoints. Materials and Methods. Changes in body weight, blood glucose, serum markers for triglycerides, free fatty acids, cholesterol, and resolvin D1, motor and sensory nerve conduction velocities and thermal sensitivity were assessed, as well as performing in vivo confocal microscopy of subepithelial corneal nerves and immunohistochemistry of nerves in the cornea and foot pad. Results. Diabetic animals failed to gain weight and had elevated blood glucose levels. Diabetic mice had slowed nerve conduction velocity, reduced innervation of the foot pad and cornea subepithelial and epithelial layers, and reduced thermal sensitivity. Monotherapy treatment with salsalate, Menhaden Oil, and resolvin D1 reduced the pathological signs of diabetic neuropathy. The combination of salsalate and Menhaden Oil also reduced signs of pathology and generated elevated plasma levels of resolvin D1 compared to other groups. Conclusions. Additional studies are needed to determine whether the combination of salsalate and Menhaden Oil may be more efficacious than monotherapy alone for the treatment of diabetic peripheral neuropathy.
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effect of treatment with salsalate Menhaden Oil combination of salsalate and Menhaden Oil or resolvin d1 of c57bl 6j type 1 diabetic mouse on neuropathic endpoints
Journal of Nutrition and Metabolism, 2016Co-Authors: Hanna Shevalye, Lawrence J. Coppey, Alexander Obrosov, Randy H. Kardon, Matthew S. YorekAbstract:Aims. In this study a streptozotocin induced type 1 diabetes mouse model was used to assess the effectiveness of salsalate, Menhaden Oil, the combination of salsalate and Menhaden Oil, or resolvin D1 on neuropathic endpoints. Materials and Methods. Changes in body weight, blood glucose, serum markers for triglycerides, free fatty acids, cholesterol, and resolvin D1, motor and sensory nerve conduction velocities and thermal sensitivity were assessed, as well as performing in vivo confocal microscopy of subepithelial corneal nerves and immunohistochemistry of nerves in the cornea and foot pad. Results. Diabetic animals failed to gain weight and had elevated blood glucose levels. Diabetic mice had slowed nerve conduction velocity, reduced innervation of the foot pad and cornea subepithelial and epithelial layers, and reduced thermal sensitivity. Monotherapy treatment with salsalate, Menhaden Oil, and resolvin D1 reduced the pathological signs of diabetic neuropathy. The combination of salsalate and Menhaden Oil also reduced signs of pathology and generated elevated plasma levels of resolvin D1 compared to other groups. Conclusions. Additional studies are needed to determine whether the combination of salsalate and Menhaden Oil may be more efficacious than monotherapy alone for the treatment of diabetic peripheral neuropathy.
Eric P. Davidson - One of the best experts on this subject based on the ideXlab platform.
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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.
Journal of diabetes research, 2018Co-Authors: Eric P. Davidson, Lawrence J. Coppey, Hanna Shevalye, Alexander Obrosov, Mark A. YorekAbstract: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.
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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
Experimental Diabetes Research, 2018Co-Authors: Eric P. Davidson, Lawrence J. Coppey, Hanna Shevalye, Alexander Obrosov, Mark A. YorekAbstract: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.
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Impaired Corneal Sensation and Nerve Loss in a Type 2 Rat Model of Chronic Diabetes Is Reversible With Combination Therapy of Menhaden Oil, α-Lipoic Acid, and Enalapril.
Cornea, 2017Co-Authors: Eric P. Davidson, Lawrence J. Coppey, Hanna Shevalye, Alexander Obrosov, Randy H. Kardon, Mark A. YorekAbstract:Purpose:This study investigated the efficacy of monotherapy versus combination of Menhaden Oil, α-lipoic acid, and enalapril on corneal sensation and morphometry and other neuropathy-related endpoints in a rat model of type 2 diabetes.Methods:Male Sprague-Dawley rats (aged 12 weeks) were fed a high-
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effect of combination therapy consisting of enalapril α lipoic acid and Menhaden Oil on diabetic neuropathy in a high fat low dose streptozotocin treated rat
European Journal of Pharmacology, 2015Co-Authors: Eric P. Davidson, Lawrence J. Coppey, Mark A. Yorek, Amey HolmesAbstract:We have previously demonstrated that treating diabetic rats with enalapril, an angiotensin converting enzyme (ACE) inhibitor, α-lipoic acid, an antioxidant, or Menhaden Oil, a natural source of omega-3 fatty acids can partially improve diabetic peripheral neuropathy. In this study we sought to determine the efficacy of combining these three treatments on vascular and neural complications in a high fat fed low dose streptozotocin treated rat, a model of type 2 diabetes. Rats were fed a high fat diet for 8 weeks followed by a 30 mg/kg dose of streptozotocin. Eight weeks after the onset of hyperglycemia diabetic rats were treated with a combination of enalapril, α-lipoic acid and Menhaden Oil. Diabetic rats not receiving treatment were continued on the high fat diet. Glucose clearance was impaired in diabetic rats and significantly improved with treatment. Diabetes caused steatosis, elevated serum lipid levels, slowing of motor and sensory nerve conduction, thermal hypoalgesia, reduction in intraepidermal nerve fiber profiles, decrease in cornea sub-basal nerve fiber length and corneal sensitivity and impairment in vascular relaxation to acetylcholine and calcitonin gene-related peptide in epineurial arterioles of the sciatic nerve. Treating diabetic rats with the combination of enalapril, α-lipoic acid and Menhaden Oil reversed all these deficits to near control levels except for motor nerve conduction velocity which was also significantly improved compared to diabetic rats but remained significantly decreased compared to control rats. These studies suggest that a combination therapeutic approach may be most effective for treating vascular and neural complications of type 2 diabetes.
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Effect of combination therapy consisting of enalapril, α-lipoic acid, and Menhaden Oil on diabetic neuropathy in a high fat/low dose streptozotocin treated rat
European journal of pharmacology, 2015Co-Authors: Eric P. Davidson, Lawrence J. Coppey, Amey Holmes, Mark A. YorekAbstract:We have previously demonstrated that treating diabetic rats with enalapril, an angiotensin converting enzyme (ACE) inhibitor, α-lipoic acid, an antioxidant, or Menhaden Oil, a natural source of omega-3 fatty acids can partially improve diabetic peripheral neuropathy. In this study we sought to determine the efficacy of combining these three treatments on vascular and neural complications in a high fat fed low dose streptozotocin treated rat, a model of type 2 diabetes. Rats were fed a high fat diet for 8 weeks followed by a 30 mg/kg dose of streptozotocin. Eight weeks after the onset of hyperglycemia diabetic rats were treated with a combination of enalapril, α-lipoic acid and Menhaden Oil. Diabetic rats not receiving treatment were continued on the high fat diet. Glucose clearance was impaired in diabetic rats and significantly improved with treatment. Diabetes caused steatosis, elevated serum lipid levels, slowing of motor and sensory nerve conduction, thermal hypoalgesia, reduction in intraepidermal nerve fiber profiles, decrease in cornea sub-basal nerve fiber length and corneal sensitivity and impairment in vascular relaxation to acetylcholine and calcitonin gene-related peptide in epineurial arterioles of the sciatic nerve. Treating diabetic rats with the combination of enalapril, α-lipoic acid and Menhaden Oil reversed all these deficits to near control levels except for motor nerve conduction velocity which was also significantly improved compared to diabetic rats but remained significantly decreased compared to control rats. These studies suggest that a combination therapeutic approach may be most effective for treating vascular and neural complications of type 2 diabetes.
Hanna Shevalye - One of the best experts on this subject based on the ideXlab platform.
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Characterization of Mice Ubiquitously Overexpressing Human 15-Lipoxygenase-1: Effect of Diabetes on Peripheral Neuropathy and Treatment with Menhaden Oil
Journal of Diabetes Research, 2021Co-Authors: Lawrence Coppey, Hanna Shevalye, Alexander Obrosov, Eric Davidson, William Paradee, Mark A. YorekAbstract:To rigorously explore the role of omega-3 polyunsaturated fatty acids (PUFA) in the treatment of diabetic peripheral neuropathy (DPN), we have created a transgenic mouse utilizing a Cre-lox promoter to control overexpression of human 15-lipoxygenase-1 (15-LOX-1). In this study, we sought to determine the effect of treating type 2 diabetic wild-type mice and transgenic mice ubiquitously overexpressing 15-LOX-1 with Menhaden Oil on endpoints related to DPN. Wild-type and transgenic mice on a C57Bl/6J background were divided into three groups. Two of each of these groups were used to create a high-fat diet/streptozotocin model for type 2 diabetes. The remaining mice were control groups. Four weeks later, one set of diabetic mice from each group was treated with Menhaden Oil for twelve weeks and then evaluated using DPN-related endpoints. Studies were also performed using dorsal root ganglion neurons isolated from wild-type and transgenic mice. Wild-type and transgenic diabetic mice developed DPN as determined by slowing of nerve conduction velocity, decreased sensory nerve fibers in the skin and cornea, and impairment of thermal and mechanical sensitivity of the hindpaw compared to their respective control mice. Although not significant, there was a trend for the severity of these DPN-related deficits to be less in the diabetic transgenic mice compared to the diabetic wild-type mice. Treating diabetic wild-type and transgenic mice with Menhaden Oil improved the DPN-related endpoints with a trend for greater improvement or protection by Menhaden Oil observed in the diabetic transgenic mice. Treating dorsal root ganglion neurons with docosahexanoic acid but not eicosapentaenoic acid significantly increased neurite outgrowth with greater efficacy observed with neurons isolated from transgenic mice. Targeting pathways that will increase the production of the anti-inflammatory metabolites of omega-3 PUFA may be an efficacious approach to developing an effective treatment for DPN.
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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.
Journal of diabetes research, 2018Co-Authors: Eric P. Davidson, Lawrence J. Coppey, Hanna Shevalye, Alexander Obrosov, Mark A. YorekAbstract: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.
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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
Experimental Diabetes Research, 2018Co-Authors: Eric P. Davidson, Lawrence J. Coppey, Hanna Shevalye, Alexander Obrosov, Mark A. YorekAbstract: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.
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Impaired Corneal Sensation and Nerve Loss in a Type 2 Rat Model of Chronic Diabetes Is Reversible With Combination Therapy of Menhaden Oil, α-Lipoic Acid, and Enalapril.
Cornea, 2017Co-Authors: Eric P. Davidson, Lawrence J. Coppey, Hanna Shevalye, Alexander Obrosov, Randy H. Kardon, Mark A. YorekAbstract:Purpose:This study investigated the efficacy of monotherapy versus combination of Menhaden Oil, α-lipoic acid, and enalapril on corneal sensation and morphometry and other neuropathy-related endpoints in a rat model of type 2 diabetes.Methods:Male Sprague-Dawley rats (aged 12 weeks) were fed a high-
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Effect of Treatment with Salsalate, Menhaden Oil, Combination of Salsalate and Menhaden Oil, or Resolvin D1 of C57Bl/6J Type 1 Diabetic Mouse on Neuropathic Endpoints.
Journal of nutrition and metabolism, 2016Co-Authors: Hanna Shevalye, Lawrence J. Coppey, Alexander Obrosov, Randy H. Kardon, Matthew S. YorekAbstract:Aims. In this study a streptozotocin induced type 1 diabetes mouse model was used to assess the effectiveness of salsalate, Menhaden Oil, the combination of salsalate and Menhaden Oil, or resolvin D1 on neuropathic endpoints. Materials and Methods. Changes in body weight, blood glucose, serum markers for triglycerides, free fatty acids, cholesterol, and resolvin D1, motor and sensory nerve conduction velocities and thermal sensitivity were assessed, as well as performing in vivo confocal microscopy of subepithelial corneal nerves and immunohistochemistry of nerves in the cornea and foot pad. Results. Diabetic animals failed to gain weight and had elevated blood glucose levels. Diabetic mice had slowed nerve conduction velocity, reduced innervation of the foot pad and cornea subepithelial and epithelial layers, and reduced thermal sensitivity. Monotherapy treatment with salsalate, Menhaden Oil, and resolvin D1 reduced the pathological signs of diabetic neuropathy. The combination of salsalate and Menhaden Oil also reduced signs of pathology and generated elevated plasma levels of resolvin D1 compared to other groups. Conclusions. Additional studies are needed to determine whether the combination of salsalate and Menhaden Oil may be more efficacious than monotherapy alone for the treatment of diabetic peripheral neuropathy.
Alexander Obrosov - One of the best experts on this subject based on the ideXlab platform.
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Characterization of Mice Ubiquitously Overexpressing Human 15-Lipoxygenase-1: Effect of Diabetes on Peripheral Neuropathy and Treatment with Menhaden Oil
Journal of Diabetes Research, 2021Co-Authors: Lawrence Coppey, Hanna Shevalye, Alexander Obrosov, Eric Davidson, William Paradee, Mark A. YorekAbstract:To rigorously explore the role of omega-3 polyunsaturated fatty acids (PUFA) in the treatment of diabetic peripheral neuropathy (DPN), we have created a transgenic mouse utilizing a Cre-lox promoter to control overexpression of human 15-lipoxygenase-1 (15-LOX-1). In this study, we sought to determine the effect of treating type 2 diabetic wild-type mice and transgenic mice ubiquitously overexpressing 15-LOX-1 with Menhaden Oil on endpoints related to DPN. Wild-type and transgenic mice on a C57Bl/6J background were divided into three groups. Two of each of these groups were used to create a high-fat diet/streptozotocin model for type 2 diabetes. The remaining mice were control groups. Four weeks later, one set of diabetic mice from each group was treated with Menhaden Oil for twelve weeks and then evaluated using DPN-related endpoints. Studies were also performed using dorsal root ganglion neurons isolated from wild-type and transgenic mice. Wild-type and transgenic diabetic mice developed DPN as determined by slowing of nerve conduction velocity, decreased sensory nerve fibers in the skin and cornea, and impairment of thermal and mechanical sensitivity of the hindpaw compared to their respective control mice. Although not significant, there was a trend for the severity of these DPN-related deficits to be less in the diabetic transgenic mice compared to the diabetic wild-type mice. Treating diabetic wild-type and transgenic mice with Menhaden Oil improved the DPN-related endpoints with a trend for greater improvement or protection by Menhaden Oil observed in the diabetic transgenic mice. Treating dorsal root ganglion neurons with docosahexanoic acid but not eicosapentaenoic acid significantly increased neurite outgrowth with greater efficacy observed with neurons isolated from transgenic mice. Targeting pathways that will increase the production of the anti-inflammatory metabolites of omega-3 PUFA may be an efficacious approach to developing an effective treatment for DPN.
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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.
Journal of diabetes research, 2018Co-Authors: Eric P. Davidson, Lawrence J. Coppey, Hanna Shevalye, Alexander Obrosov, Mark A. YorekAbstract: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.
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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
Experimental Diabetes Research, 2018Co-Authors: Eric P. Davidson, Lawrence J. Coppey, Hanna Shevalye, Alexander Obrosov, Mark A. YorekAbstract: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.
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Impaired Corneal Sensation and Nerve Loss in a Type 2 Rat Model of Chronic Diabetes Is Reversible With Combination Therapy of Menhaden Oil, α-Lipoic Acid, and Enalapril.
Cornea, 2017Co-Authors: Eric P. Davidson, Lawrence J. Coppey, Hanna Shevalye, Alexander Obrosov, Randy H. Kardon, Mark A. YorekAbstract:Purpose:This study investigated the efficacy of monotherapy versus combination of Menhaden Oil, α-lipoic acid, and enalapril on corneal sensation and morphometry and other neuropathy-related endpoints in a rat model of type 2 diabetes.Methods:Male Sprague-Dawley rats (aged 12 weeks) were fed a high-
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Effect of Treatment with Salsalate, Menhaden Oil, Combination of Salsalate and Menhaden Oil, or Resolvin D1 of C57Bl/6J Type 1 Diabetic Mouse on Neuropathic Endpoints.
Journal of nutrition and metabolism, 2016Co-Authors: Hanna Shevalye, Lawrence J. Coppey, Alexander Obrosov, Randy H. Kardon, Matthew S. YorekAbstract:Aims. In this study a streptozotocin induced type 1 diabetes mouse model was used to assess the effectiveness of salsalate, Menhaden Oil, the combination of salsalate and Menhaden Oil, or resolvin D1 on neuropathic endpoints. Materials and Methods. Changes in body weight, blood glucose, serum markers for triglycerides, free fatty acids, cholesterol, and resolvin D1, motor and sensory nerve conduction velocities and thermal sensitivity were assessed, as well as performing in vivo confocal microscopy of subepithelial corneal nerves and immunohistochemistry of nerves in the cornea and foot pad. Results. Diabetic animals failed to gain weight and had elevated blood glucose levels. Diabetic mice had slowed nerve conduction velocity, reduced innervation of the foot pad and cornea subepithelial and epithelial layers, and reduced thermal sensitivity. Monotherapy treatment with salsalate, Menhaden Oil, and resolvin D1 reduced the pathological signs of diabetic neuropathy. The combination of salsalate and Menhaden Oil also reduced signs of pathology and generated elevated plasma levels of resolvin D1 compared to other groups. Conclusions. Additional studies are needed to determine whether the combination of salsalate and Menhaden Oil may be more efficacious than monotherapy alone for the treatment of diabetic peripheral neuropathy.