The Experts below are selected from a list of 264 Experts worldwide ranked by ideXlab platform
Motoaki Saito - One of the best experts on this subject based on the ideXlab platform.
-
effects of n Hexacosanol on nitric oxide synthase system in diabetic rat nephropathy
Molecular and Cellular Biochemistry, 2008Co-Authors: Shinichi Okada, Motoaki Saito, Takuya Hanada, Keisuke Satoh, Emi Kazuyama, Yasuo Kawaba, Atsushi Hayashi, Susumu KanzakiAbstract:We attempted to clarify the effects of cyclohexenonic long-chain fatty alcohol (N-Hexacosanol) on nitric oxide synthase (NOS) in streptozotocin-induced diabetic nephropathy. After induction of experimental diabetes with streptozotocin, rats were maintained for 8 weeks with or without treatment by N-Hexacosanol (8 mg/kg i.p. every day). Urinary albumin excretion, blood chemistry, immunoblot analysis, and real-time polymerase chain reactions (real-time PCR) of endothelial nitric oxide synthase (eNOS), inducible NOS (iNOS), and neuronal NOS (nNOS) were investigated. Although N-Hexacosanol had no effects on serum glucose or insulin level, it normalized serum creatinine and urinary albumin excretion. N-Hexacosanol was found to improve the diabetes-induced alterations in the eNOS, iNOS, and nNOS protein and their mRNA levels. Histologically, N-Hexacosanol inhibited the progression to glomerular sclerosis. Our data suggest that N-Hexacosanol improves diabetes-induced NOS alterations in the kidney, resulting in the amelioration of diabetic nephropathy.
-
Ability of cyclohexenonic long-chain fatty alcohol to ameliorate diabetes-induced cystopathy in the rat.
Pharmacology, 2007Co-Authors: Emi Kazuyama, Motoaki Saito, Shinichi Okada, Keisuke SatohAbstract:We investigated the pharmacological effects of N-Hexacosanol on diabetic rat detrusor. Eight-week-old male Sprague-Dawley rats were randomly divided into 4 groups: diabetic rats induced by 50 mg/kg in
-
n Hexacosanol prevents diabetes induced rat ileal dysfunction without qualitative alteration of the muscarinic receptor system
Biomedical Research-tokyo, 2007Co-Authors: Naho Narimatsu, Motoaki Saito, Yukako Kinoshita, Itaru Satoh, Hiroto Suzuki, Masashi Yamada, Shinichi Okada, Emi Kazuyama, Yoshie Hisadome, Keisuke SatohAbstract:We evaluated the effects of N-Hexacosanol, a cyclohexenonic long-chain fatty alcohol, on muscarinic receptors in diabetic rat ileal dysfunction. Eight-week-old male SD rats were divided into four groups. After induction of diabetes (streptozotocin 50 mg/kg, i.p.), three groups were maintained for eight weeks with treatment by N-Hexacosanol (0, 2 or 8 mg/kg, s.c. every day). Ileum function was investigated by organ bath studies using carbachol and KCl, and the expression levels of muscarinic M2 and M3 receptors were investigated by real-time polymerase chain reaction. Various concentrations of subtype-selective muscarinic antagonists, i.e., atropine (non-selective), pirenzepine (M1 selective), methoctramine (M2 selective), and 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, M1/M3 selective), were used in this study. In the presence and absence of these antagonists, contractile response curves to increasing concentrations of carbachol were investigated. Treatment with N-Hexacosanol did not alter the diabetic status of the rats, but did significantly prevent the carbachol-induced hypercontractility in diabetic rat ileum. Estimation of the pA2 values for atropine, pirenzepine, methoctramine, and 4-DAMP indicated that the carbacholinduced contractile response in the ileum is mainly mediated through the muscarinic M3 receptor subtype in all groups. Furthermore, N-Hexacosanol significantly prevented the diabetes-induced up-regulation of intestinal muscarinic M2 and M3 receptor mRNAs in streptozotocin-diabetic rats. Our data indicated that N-Hexacosanol exerts preventive effects with respect to carbachol-induced hypercontractility in the diabetic rat ileum without qualitative alteration of the muscarinic receptor system.
-
Cyclohexenonic long-chain fatty alcohol has therapeutic effects on diabetes-induced angiopathy in the rat aorta.
European journal of pharmacology, 2007Co-Authors: Chiko Shinbori, Motoaki Saito, Yukako Kinoshita, Itaru Satoh, Tomoharu Kono, Takuya Hanada, Hiroto Suzuki, Eiji Nanba, Kaori Adachi, Masashi YamadaAbstract:We studied the effects of cyclohexenonic long-chain fatty alcohol (N-Hexacosanol) on diabetes-induced angiopathy in the rat aorta. Male Sprague-Dawley rats were divided into 4 groups, a control group and 3 other groups in which diabetes was induced by streptozotocin (50 mg/kg i.p.). Four weeks after the induction of diabetes, the 3 groups received treatment with either vehicle or N-Hexacosanol (2 or 8 mg/kg, i.p. every day) for another 4 weeks. To determine the mechanisms of diabetic vascular dysfunction and the effects of N-Hexacosanol, we conducted organ bath studies and real-time polymerase chain reaction on muscarinic M(3) receptor, and endothelial and inducible nitric oxide synthase (eNOS and iNOS) mRNAs in the rat aorta. Treatment with N-Hexacosanol did not alter the diabetic status, but improved the diabetes-induced hypercontraction produced by norepinephrine and the damaged endothelium-dependent relaxation of the rat aorta induced by acetylcholine. Furthermore, in the diabetic rats, both muscarinic M(3) receptor and iNOS mRNAs were significantly increased, and N-Hexacosanol reversed these upregulations. However, the expression of eNOS mRNA showed no change in all groups. These results indicate that N-Hexacosanol has beneficial effects on functional dysfunction and reverses the upregulation of muscarinic M(3) receptor and iNOS mRNAs in the diabetic rat aorta.
-
n Hexacosanol reverses diabetic induced muscarinic hypercontractility of ileum in the rat
European Journal of Pharmacology, 2006Co-Authors: Chiko Shinbori, Motoaki Saito, Yukako Kinoshita, Itaru Satoh, Tomoharu Kono, Takuya Hanada, Hiroto Suzuki, Eiji Nanba, Kaori Adachi, Masashi YamadaAbstract:Abstract Diabetic neuropathy, a major complication of diabetes mellitus, is associated with development of gastrointestinal motility dysfunction and autonomic neuropathy. N-Hexacosanol has neurotrophic effects and exhibits a wide variety of biological actions. In this study, we investigated the effects of cyclohexenonic long-chain fatty alcohol (N-Hexacosanol) on streptozotocin-diabetic hypercontractility in the rat ileum longitudinal muscles. Treatment with N-Hexacosanol did not alter the diabetic status of the animals, i.e., body weight, serum glucose, and serum insulin levels, but significantly restored the thickness of intestine wall and ameliorated diabetes-induced hypercontractility of the rat ileum in a dose-dependent manner. Furthermore, N-Hexacosanol reversed the diabetes-induced upregulation of intestinal muscarinic M2 and M3 receptors mRNAs in the streptozotocin-diabetic rats. These results indicate that N-Hexacosanol has therapeutic effects on hypercontractility in the diabetic ileum by ameliorating overexpression of muscarinic M2 and M3 receptors mRNAs.
Keisuke Satoh - One of the best experts on this subject based on the ideXlab platform.
-
effects of n Hexacosanol on nitric oxide synthase system in diabetic rat nephropathy
Molecular and Cellular Biochemistry, 2008Co-Authors: Shinichi Okada, Motoaki Saito, Takuya Hanada, Keisuke Satoh, Emi Kazuyama, Yasuo Kawaba, Atsushi Hayashi, Susumu KanzakiAbstract:We attempted to clarify the effects of cyclohexenonic long-chain fatty alcohol (N-Hexacosanol) on nitric oxide synthase (NOS) in streptozotocin-induced diabetic nephropathy. After induction of experimental diabetes with streptozotocin, rats were maintained for 8 weeks with or without treatment by N-Hexacosanol (8 mg/kg i.p. every day). Urinary albumin excretion, blood chemistry, immunoblot analysis, and real-time polymerase chain reactions (real-time PCR) of endothelial nitric oxide synthase (eNOS), inducible NOS (iNOS), and neuronal NOS (nNOS) were investigated. Although N-Hexacosanol had no effects on serum glucose or insulin level, it normalized serum creatinine and urinary albumin excretion. N-Hexacosanol was found to improve the diabetes-induced alterations in the eNOS, iNOS, and nNOS protein and their mRNA levels. Histologically, N-Hexacosanol inhibited the progression to glomerular sclerosis. Our data suggest that N-Hexacosanol improves diabetes-induced NOS alterations in the kidney, resulting in the amelioration of diabetic nephropathy.
-
Ability of cyclohexenonic long-chain fatty alcohol to ameliorate diabetes-induced cystopathy in the rat.
Pharmacology, 2007Co-Authors: Emi Kazuyama, Motoaki Saito, Shinichi Okada, Keisuke SatohAbstract:We investigated the pharmacological effects of N-Hexacosanol on diabetic rat detrusor. Eight-week-old male Sprague-Dawley rats were randomly divided into 4 groups: diabetic rats induced by 50 mg/kg in
-
n Hexacosanol prevents diabetes induced rat ileal dysfunction without qualitative alteration of the muscarinic receptor system
Biomedical Research-tokyo, 2007Co-Authors: Naho Narimatsu, Motoaki Saito, Yukako Kinoshita, Itaru Satoh, Hiroto Suzuki, Masashi Yamada, Shinichi Okada, Emi Kazuyama, Yoshie Hisadome, Keisuke SatohAbstract:We evaluated the effects of N-Hexacosanol, a cyclohexenonic long-chain fatty alcohol, on muscarinic receptors in diabetic rat ileal dysfunction. Eight-week-old male SD rats were divided into four groups. After induction of diabetes (streptozotocin 50 mg/kg, i.p.), three groups were maintained for eight weeks with treatment by N-Hexacosanol (0, 2 or 8 mg/kg, s.c. every day). Ileum function was investigated by organ bath studies using carbachol and KCl, and the expression levels of muscarinic M2 and M3 receptors were investigated by real-time polymerase chain reaction. Various concentrations of subtype-selective muscarinic antagonists, i.e., atropine (non-selective), pirenzepine (M1 selective), methoctramine (M2 selective), and 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, M1/M3 selective), were used in this study. In the presence and absence of these antagonists, contractile response curves to increasing concentrations of carbachol were investigated. Treatment with N-Hexacosanol did not alter the diabetic status of the rats, but did significantly prevent the carbachol-induced hypercontractility in diabetic rat ileum. Estimation of the pA2 values for atropine, pirenzepine, methoctramine, and 4-DAMP indicated that the carbacholinduced contractile response in the ileum is mainly mediated through the muscarinic M3 receptor subtype in all groups. Furthermore, N-Hexacosanol significantly prevented the diabetes-induced up-regulation of intestinal muscarinic M2 and M3 receptor mRNAs in streptozotocin-diabetic rats. Our data indicated that N-Hexacosanol exerts preventive effects with respect to carbachol-induced hypercontractility in the diabetic rat ileum without qualitative alteration of the muscarinic receptor system.
-
n Hexacosanol ameliorates streptozotocin induced diabetic rat nephropathy
European Journal of Pharmacology, 2006Co-Authors: Motoaki Saito, Yukako Kinoshita, Itaru Satoh, Chiko Shinbori, Tomoharu Kono, Takuya Hanada, Jiro Uemasu, Hiroto Suzuki, Masashi Yamada, Keisuke SatohAbstract:Abstract In this study we investigated the effects of N-Hexacosanol on streptozotocin-induced rat diabetic nephropathy. Diabetes was induced in 8-week-old male Sprague–Dawley rats by administering an intraperitoneal injection of streptozotocin (50 mg/kg). The rats were divided into four groups and maintained for 8 weeks: control rats, diabetic rats without treatment with N-Hexacosanol, and diabetic rats treated with N-Hexacosanol (2 mg/kg and 8 mg/kg i.p. every day). Although N-Hexacosanol failed to modify the diabetic status, increases in serum creatinine as well as in kidney weight were significantly reduced. The malonaldehyde and transforming growth factor beta-1 (TGF-β1) concentrations as well as the protein kinase C (PKC) activities in the diabetic kidney were significantly higher than those of the control, which were decreased by treatment with N-Hexacosanol. Histological examinations revealed that N-Hexacosanol significantly ameliorated diabetic-induced tubulointerstitial pathological changes. Our data suggest that N-Hexacosanol could prevent increases in the malonaldehyde and TGF-β1 concentrations and PKC activities in the kidney, and ameliorate diabetic-induced nephropathy.
-
Ability of cyclohexenonic long-chain fatty alcohol to reverse diabetes-induced cystopathy in the rat.
European Urology, 2006Co-Authors: Motoaki Saito, Yukako Kinoshita, Itaru Satoh, Chiko Shinbori, Hiroto Suzuki, Masashi Yamada, T. Watanabe, Keisuke SatohAbstract:Abstract Objectives We investigated the ability of 3-(15 hydroxypentadecyl)-2,4,4-trimethyl-2-cyclohexen 1-one (N-Hexacosanol), a neurotrophic substance, to reverse diabetes-induced cystopathy in the rat. Materials and methods Eight-week-old male Sprague-Dawley rats were divided randomly into four age-matched groups. In three of these groups, diabetes was induced by streptozotocin (STZ; 50mg/kg intraperitoneal [IP]). Four weeks after the induction of diabetes, the three groups received another 4 weeks of treatment by vehicle or N-Hexacosanol (2 or 8mg/kg IP every day). The serum glucose and serum insulin levels were determined, and the bladder functions were estimated by voiding behavior studies, cystometric studies, and functional studies using carbachol and KCl. The participation levels of M 2 and M 3 receptors were investigated by real-time polymerase chain reaction and immunohistochemical staining. Typical hematoxylin-eosin staining was also performed. Results Treatment with N-Hexacosanol did not alter the rats' diabetic status, but did significantly improve the diabetes-induced dysfunction of the detrusor in a dose-dependent manner. Furthermore, N-Hexacosanol significantly reversed the upregulation of muscarinic M 2 and M 3 receptor messenger RNAs (mRNAs) in STZ-diabetic rats. Muscarinic M 2 and M 3 receptors were localized in detrusor and urothelium, and there was no difference between any of the groups in the distribution of muscarinic M 2 and M 3 receptors. Conclusions These results indicate that N-Hexacosanol has a beneficial effect on hyperreactivity in the diabetic detrusor by ameliorating overexpression of muscarinic M 2 and M 3 receptor mRNAs.
Masashi Yamada - One of the best experts on this subject based on the ideXlab platform.
-
n Hexacosanol prevents diabetes induced rat ileal dysfunction without qualitative alteration of the muscarinic receptor system
Biomedical Research-tokyo, 2007Co-Authors: Naho Narimatsu, Motoaki Saito, Yukako Kinoshita, Itaru Satoh, Hiroto Suzuki, Masashi Yamada, Shinichi Okada, Emi Kazuyama, Yoshie Hisadome, Keisuke SatohAbstract:We evaluated the effects of N-Hexacosanol, a cyclohexenonic long-chain fatty alcohol, on muscarinic receptors in diabetic rat ileal dysfunction. Eight-week-old male SD rats were divided into four groups. After induction of diabetes (streptozotocin 50 mg/kg, i.p.), three groups were maintained for eight weeks with treatment by N-Hexacosanol (0, 2 or 8 mg/kg, s.c. every day). Ileum function was investigated by organ bath studies using carbachol and KCl, and the expression levels of muscarinic M2 and M3 receptors were investigated by real-time polymerase chain reaction. Various concentrations of subtype-selective muscarinic antagonists, i.e., atropine (non-selective), pirenzepine (M1 selective), methoctramine (M2 selective), and 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, M1/M3 selective), were used in this study. In the presence and absence of these antagonists, contractile response curves to increasing concentrations of carbachol were investigated. Treatment with N-Hexacosanol did not alter the diabetic status of the rats, but did significantly prevent the carbachol-induced hypercontractility in diabetic rat ileum. Estimation of the pA2 values for atropine, pirenzepine, methoctramine, and 4-DAMP indicated that the carbacholinduced contractile response in the ileum is mainly mediated through the muscarinic M3 receptor subtype in all groups. Furthermore, N-Hexacosanol significantly prevented the diabetes-induced up-regulation of intestinal muscarinic M2 and M3 receptor mRNAs in streptozotocin-diabetic rats. Our data indicated that N-Hexacosanol exerts preventive effects with respect to carbachol-induced hypercontractility in the diabetic rat ileum without qualitative alteration of the muscarinic receptor system.
-
Cyclohexenonic long-chain fatty alcohol has therapeutic effects on diabetes-induced angiopathy in the rat aorta.
European journal of pharmacology, 2007Co-Authors: Chiko Shinbori, Motoaki Saito, Yukako Kinoshita, Itaru Satoh, Tomoharu Kono, Takuya Hanada, Hiroto Suzuki, Eiji Nanba, Kaori Adachi, Masashi YamadaAbstract:We studied the effects of cyclohexenonic long-chain fatty alcohol (N-Hexacosanol) on diabetes-induced angiopathy in the rat aorta. Male Sprague-Dawley rats were divided into 4 groups, a control group and 3 other groups in which diabetes was induced by streptozotocin (50 mg/kg i.p.). Four weeks after the induction of diabetes, the 3 groups received treatment with either vehicle or N-Hexacosanol (2 or 8 mg/kg, i.p. every day) for another 4 weeks. To determine the mechanisms of diabetic vascular dysfunction and the effects of N-Hexacosanol, we conducted organ bath studies and real-time polymerase chain reaction on muscarinic M(3) receptor, and endothelial and inducible nitric oxide synthase (eNOS and iNOS) mRNAs in the rat aorta. Treatment with N-Hexacosanol did not alter the diabetic status, but improved the diabetes-induced hypercontraction produced by norepinephrine and the damaged endothelium-dependent relaxation of the rat aorta induced by acetylcholine. Furthermore, in the diabetic rats, both muscarinic M(3) receptor and iNOS mRNAs were significantly increased, and N-Hexacosanol reversed these upregulations. However, the expression of eNOS mRNA showed no change in all groups. These results indicate that N-Hexacosanol has beneficial effects on functional dysfunction and reverses the upregulation of muscarinic M(3) receptor and iNOS mRNAs in the diabetic rat aorta.
-
n Hexacosanol reverses diabetic induced muscarinic hypercontractility of ileum in the rat
European Journal of Pharmacology, 2006Co-Authors: Chiko Shinbori, Motoaki Saito, Yukako Kinoshita, Itaru Satoh, Tomoharu Kono, Takuya Hanada, Hiroto Suzuki, Eiji Nanba, Kaori Adachi, Masashi YamadaAbstract:Abstract Diabetic neuropathy, a major complication of diabetes mellitus, is associated with development of gastrointestinal motility dysfunction and autonomic neuropathy. N-Hexacosanol has neurotrophic effects and exhibits a wide variety of biological actions. In this study, we investigated the effects of cyclohexenonic long-chain fatty alcohol (N-Hexacosanol) on streptozotocin-diabetic hypercontractility in the rat ileum longitudinal muscles. Treatment with N-Hexacosanol did not alter the diabetic status of the animals, i.e., body weight, serum glucose, and serum insulin levels, but significantly restored the thickness of intestine wall and ameliorated diabetes-induced hypercontractility of the rat ileum in a dose-dependent manner. Furthermore, N-Hexacosanol reversed the diabetes-induced upregulation of intestinal muscarinic M2 and M3 receptors mRNAs in the streptozotocin-diabetic rats. These results indicate that N-Hexacosanol has therapeutic effects on hypercontractility in the diabetic ileum by ameliorating overexpression of muscarinic M2 and M3 receptors mRNAs.
-
n Hexacosanol ameliorates streptozotocin induced diabetic rat nephropathy
European Journal of Pharmacology, 2006Co-Authors: Motoaki Saito, Yukako Kinoshita, Itaru Satoh, Chiko Shinbori, Tomoharu Kono, Takuya Hanada, Jiro Uemasu, Hiroto Suzuki, Masashi Yamada, Keisuke SatohAbstract:Abstract In this study we investigated the effects of N-Hexacosanol on streptozotocin-induced rat diabetic nephropathy. Diabetes was induced in 8-week-old male Sprague–Dawley rats by administering an intraperitoneal injection of streptozotocin (50 mg/kg). The rats were divided into four groups and maintained for 8 weeks: control rats, diabetic rats without treatment with N-Hexacosanol, and diabetic rats treated with N-Hexacosanol (2 mg/kg and 8 mg/kg i.p. every day). Although N-Hexacosanol failed to modify the diabetic status, increases in serum creatinine as well as in kidney weight were significantly reduced. The malonaldehyde and transforming growth factor beta-1 (TGF-β1) concentrations as well as the protein kinase C (PKC) activities in the diabetic kidney were significantly higher than those of the control, which were decreased by treatment with N-Hexacosanol. Histological examinations revealed that N-Hexacosanol significantly ameliorated diabetic-induced tubulointerstitial pathological changes. Our data suggest that N-Hexacosanol could prevent increases in the malonaldehyde and TGF-β1 concentrations and PKC activities in the kidney, and ameliorate diabetic-induced nephropathy.
-
Ability of cyclohexenonic long-chain fatty alcohol to reverse diabetes-induced cystopathy in the rat.
European Urology, 2006Co-Authors: Motoaki Saito, Yukako Kinoshita, Itaru Satoh, Chiko Shinbori, Hiroto Suzuki, Masashi Yamada, T. Watanabe, Keisuke SatohAbstract:Abstract Objectives We investigated the ability of 3-(15 hydroxypentadecyl)-2,4,4-trimethyl-2-cyclohexen 1-one (N-Hexacosanol), a neurotrophic substance, to reverse diabetes-induced cystopathy in the rat. Materials and methods Eight-week-old male Sprague-Dawley rats were divided randomly into four age-matched groups. In three of these groups, diabetes was induced by streptozotocin (STZ; 50mg/kg intraperitoneal [IP]). Four weeks after the induction of diabetes, the three groups received another 4 weeks of treatment by vehicle or N-Hexacosanol (2 or 8mg/kg IP every day). The serum glucose and serum insulin levels were determined, and the bladder functions were estimated by voiding behavior studies, cystometric studies, and functional studies using carbachol and KCl. The participation levels of M 2 and M 3 receptors were investigated by real-time polymerase chain reaction and immunohistochemical staining. Typical hematoxylin-eosin staining was also performed. Results Treatment with N-Hexacosanol did not alter the rats' diabetic status, but did significantly improve the diabetes-induced dysfunction of the detrusor in a dose-dependent manner. Furthermore, N-Hexacosanol significantly reversed the upregulation of muscarinic M 2 and M 3 receptor messenger RNAs (mRNAs) in STZ-diabetic rats. Muscarinic M 2 and M 3 receptors were localized in detrusor and urothelium, and there was no difference between any of the groups in the distribution of muscarinic M 2 and M 3 receptors. Conclusions These results indicate that N-Hexacosanol has a beneficial effect on hyperreactivity in the diabetic detrusor by ameliorating overexpression of muscarinic M 2 and M 3 receptor mRNAs.
Jacques Borg - One of the best experts on this subject based on the ideXlab platform.
-
enhancement of mouse sciatic nerve regeneration by the long chain fatty alcohol n Hexacosanol
Experimental Neurology, 1996Co-Authors: Mimoun Azzouz, Philippe F Kennel, J M Warter, Philippe Poindron, Jacques BorgAbstract:Abstract The purpose of the present study was to determine the effects ofn-Hexacosanol (hexa) on nerve regeneration. Hexa, a long chain fatty alcohol has been shown to possess neurotrophic properties on cultured neurons and to attenuate the degeneration of cholinergic neurons after injury. The effects of daily intraperitoneal injections of hexa (1 mg/kg) on regeneration of nerve fibers were studied in mice following a sciatic nerve crush. Measurement of axonal regeneration using the pinch test 7 days postlesion showed a 40% increase of the regeneration rate of sensory fibers in hexa-treated mice compared to controls (1.67 ± 0.15 mm/day and 1.09 ± 0.03 mm/day, respectively). The recovery of neuromuscular function was significantly improved, as shown by quantitative electromyography and sensorimotor tests. Clinical signs of recovery evaluated with toe spreading reflex appeared earlier in hexa group than in control animals. Electrophysiological recordings were performed each 3 days during 34 days following nerve injury. Higher values of the compound muscle action potential (CMAP) were obtained in hexa-treated animals that correspond to an improved regeneration. Moreover, hexa induced a significantly faster regeneration rate (hexa: 2.87 ± 0.15 mV/day; control: 2.00 ± 0.06 mV/day), as measured by the slope of CMAP increase (44% enhancement). A morphometric analysis performed 7 days following crush showed an increased number of regenerating fibers, as well as increased diameter and thickness of the myelin in hexa-treated mice. Thus, hexa increased the regeneration of both sensory and motor axons in lesioned nerve, leading to an improved functional recovery.
-
Enhancement of Mouse Sciatic Nerve Regeneration by the Long Chain Fatty Alcohol,N-Hexacosanol
Experimental Neurology, 1996Co-Authors: Mimoun Azzouz, Philippe F Kennel, J M Warter, Philippe Poindron, Jacques BorgAbstract:The purpose of the present study was to determine the effects of n-Hexacosanol (hexa) on nerve regeneration. Hexa, a long chain fatty alcohol has been shown to possess neurotrophic properties on cultured neurons and to attenuate the degeneration of cholinergic neurons after injury. The effects of daily intraperitoneal injections of hexa (1 mg/kg) on regeneration of nerve fibers were studied in mice following a sciatic nerve crush. Measurement of axonal regeneration using the pinch test 7 days postlesion showed a 40% increase of the regeneration rate of sensory fibers in hexa-treated mice compared to controls (1.67 +/- 0.15 mm/day and 1.09 +/- 0.03 mm/day, respectively). The recovery of neuromuscular function was significantly improved, as shown by quantitative electromyography and and sensorimotor tests. Clinical signs of recovery evaluation with toe spreading reflex appeared earlier in hexa group than in control animals. Electrophysiological recordings were performed each 3 days during 34 days following nerve injury. Higher values of the compound muscle action potential (CMAP) were obtained in hexa-treated animals that correspond to an improved regeneration. Moreover, hexa induced a significantly faster regeneration rate (hexa: 2.87 +/- 0.15 mV/day; control: 2.00 +/- 0.06 mV/day), as measured by the slope of CMAP increase (44% enhancement). A morphometric analysis performed 7 days following crush showed an increased number of regenerating fibers, as well as increased diameter and thickness of the myelin in hexa-treated mice. Thus, hexa increased the regeneration of both sensory and motor axons in lesioned nerve, leading to an improved functional recovery.
-
effect of n Hexacosanol on insulin secretion in the rat
European Journal of Pharmacology, 1995Co-Authors: C Damge, D Hillairebuys, Michele Koenig, R Gross, A Hoeltzel, J Chapal, Ginette Balboni, Jacques Borg, Gerard RibesAbstract:Abstract n-Hexacosanol, a long-chain satured fatty alcohol extracted from Hygrophyla erecta Hochr., has been recently shown to exert neurotrophic properties on central neurons and to stimulate phagocytosis in macrophages. The present work was designed to investigate the effects of Hexacosanol on stimulated insulin secretion in vivo and in vitro. In anaesthetized rats, Hexacosanol (2 mg/kg i.p.) induced a reduction of the insulin response to an intravenous glucose tolerance test (0.3 g/kg) with a consequent increase in hyperglycaemia. In vitro, in the isolated perfused pancreas, Hexacosanol at the concentration of 10−7 M clearly reduced the two phases of glucose-induced insulin secretion. At the higher concentration (10−5 M), Hexacosanol was no longer able to exert an inhibition of glucose-induced insulin release; surprisingly a stimulating effect occurred which was of the same magnitude as in control experiments with Tween alone, at the concentration used to dissolve Hexacosanol. In isolated perifused islets, 22 mM glucose-stimulated insulin release was also inhibited by Hexacosanol at the concentrations of 10−9 M and 10−7 M, but not at 10−5 M. In contrast, insulin secretion induced by arginine (20 mM) was not affected by the different concentrations of Hexacosanol. It is concluded that n-Hexacosanol at 10−9 M and 10−7 M exerts an inhibitory effect on insulin secretion stimulated by glucose in vivo and in vitro in the rat, suggesting a direct effect on islets of Langerhans.
-
the neurotrophic factor n Hexacosanol reduces the neuronal damage induced by the neurotoxin kainic acid
Journal of Neuroscience Research, 1991Co-Authors: Jacques BorgAbstract:The long-chain fatty alcohol, n-Hexacosanol, has been shown to possess neurotrophic properties in vitro on rat CNS cultures (Borg et al., 1987) and to promote the survival of septal cholinergic neurons after experimental axotomy (Borg et al., 1990). Long-chain alcohols have also been shown to be synthesized and metabolised by rat brain during development (Bishop and Hayra, 1981; Natarajan et al., 1984). The present study was undertaken in order to find out if a nonproteic neurotrophic factor like n-Hexacosanol may be able to reduce the neuronal damages induced by the excitatory amino acid, kainic acid. When administered chronically by intraperitoneal injection, Hexacosanol (1 mg/kg) protected the pyramidal neurons of the hippocampus from the neurotoxic degeneration induced by an intracerebroventricular infusion of kainic acid in rats; the extent of the damage was limited to a small part of the CA3 region. Mor-phometric analysis showed that 72% of the neurons that would have died following kainic acid injection were spared by Hexacosanol. Moreover the increased locomotor activity induced by the neurotoxin was also inhibited by Hexacosanol and the behavioral effect was statistically correlated to the extent of neuronal loss. The present study suggests a possible role for nonproteic neurotrophic compounds against neurotoxic damages on central neurons. Moreover the peripheral administration of Hexacosanol may lead to a significant breakthrough in the treatment of excito-toxin-related human diseases.
Takuya Hanada - One of the best experts on this subject based on the ideXlab platform.
-
effects of n Hexacosanol on nitric oxide synthase system in diabetic rat nephropathy
Molecular and Cellular Biochemistry, 2008Co-Authors: Shinichi Okada, Motoaki Saito, Takuya Hanada, Keisuke Satoh, Emi Kazuyama, Yasuo Kawaba, Atsushi Hayashi, Susumu KanzakiAbstract:We attempted to clarify the effects of cyclohexenonic long-chain fatty alcohol (N-Hexacosanol) on nitric oxide synthase (NOS) in streptozotocin-induced diabetic nephropathy. After induction of experimental diabetes with streptozotocin, rats were maintained for 8 weeks with or without treatment by N-Hexacosanol (8 mg/kg i.p. every day). Urinary albumin excretion, blood chemistry, immunoblot analysis, and real-time polymerase chain reactions (real-time PCR) of endothelial nitric oxide synthase (eNOS), inducible NOS (iNOS), and neuronal NOS (nNOS) were investigated. Although N-Hexacosanol had no effects on serum glucose or insulin level, it normalized serum creatinine and urinary albumin excretion. N-Hexacosanol was found to improve the diabetes-induced alterations in the eNOS, iNOS, and nNOS protein and their mRNA levels. Histologically, N-Hexacosanol inhibited the progression to glomerular sclerosis. Our data suggest that N-Hexacosanol improves diabetes-induced NOS alterations in the kidney, resulting in the amelioration of diabetic nephropathy.
-
Cyclohexenonic long-chain fatty alcohol has therapeutic effects on diabetes-induced angiopathy in the rat aorta.
European journal of pharmacology, 2007Co-Authors: Chiko Shinbori, Motoaki Saito, Yukako Kinoshita, Itaru Satoh, Tomoharu Kono, Takuya Hanada, Hiroto Suzuki, Eiji Nanba, Kaori Adachi, Masashi YamadaAbstract:We studied the effects of cyclohexenonic long-chain fatty alcohol (N-Hexacosanol) on diabetes-induced angiopathy in the rat aorta. Male Sprague-Dawley rats were divided into 4 groups, a control group and 3 other groups in which diabetes was induced by streptozotocin (50 mg/kg i.p.). Four weeks after the induction of diabetes, the 3 groups received treatment with either vehicle or N-Hexacosanol (2 or 8 mg/kg, i.p. every day) for another 4 weeks. To determine the mechanisms of diabetic vascular dysfunction and the effects of N-Hexacosanol, we conducted organ bath studies and real-time polymerase chain reaction on muscarinic M(3) receptor, and endothelial and inducible nitric oxide synthase (eNOS and iNOS) mRNAs in the rat aorta. Treatment with N-Hexacosanol did not alter the diabetic status, but improved the diabetes-induced hypercontraction produced by norepinephrine and the damaged endothelium-dependent relaxation of the rat aorta induced by acetylcholine. Furthermore, in the diabetic rats, both muscarinic M(3) receptor and iNOS mRNAs were significantly increased, and N-Hexacosanol reversed these upregulations. However, the expression of eNOS mRNA showed no change in all groups. These results indicate that N-Hexacosanol has beneficial effects on functional dysfunction and reverses the upregulation of muscarinic M(3) receptor and iNOS mRNAs in the diabetic rat aorta.
-
n Hexacosanol reverses diabetic induced muscarinic hypercontractility of ileum in the rat
European Journal of Pharmacology, 2006Co-Authors: Chiko Shinbori, Motoaki Saito, Yukako Kinoshita, Itaru Satoh, Tomoharu Kono, Takuya Hanada, Hiroto Suzuki, Eiji Nanba, Kaori Adachi, Masashi YamadaAbstract:Abstract Diabetic neuropathy, a major complication of diabetes mellitus, is associated with development of gastrointestinal motility dysfunction and autonomic neuropathy. N-Hexacosanol has neurotrophic effects and exhibits a wide variety of biological actions. In this study, we investigated the effects of cyclohexenonic long-chain fatty alcohol (N-Hexacosanol) on streptozotocin-diabetic hypercontractility in the rat ileum longitudinal muscles. Treatment with N-Hexacosanol did not alter the diabetic status of the animals, i.e., body weight, serum glucose, and serum insulin levels, but significantly restored the thickness of intestine wall and ameliorated diabetes-induced hypercontractility of the rat ileum in a dose-dependent manner. Furthermore, N-Hexacosanol reversed the diabetes-induced upregulation of intestinal muscarinic M2 and M3 receptors mRNAs in the streptozotocin-diabetic rats. These results indicate that N-Hexacosanol has therapeutic effects on hypercontractility in the diabetic ileum by ameliorating overexpression of muscarinic M2 and M3 receptors mRNAs.
-
n Hexacosanol ameliorates streptozotocin induced diabetic rat nephropathy
European Journal of Pharmacology, 2006Co-Authors: Motoaki Saito, Yukako Kinoshita, Itaru Satoh, Chiko Shinbori, Tomoharu Kono, Takuya Hanada, Jiro Uemasu, Hiroto Suzuki, Masashi Yamada, Keisuke SatohAbstract:Abstract In this study we investigated the effects of N-Hexacosanol on streptozotocin-induced rat diabetic nephropathy. Diabetes was induced in 8-week-old male Sprague–Dawley rats by administering an intraperitoneal injection of streptozotocin (50 mg/kg). The rats were divided into four groups and maintained for 8 weeks: control rats, diabetic rats without treatment with N-Hexacosanol, and diabetic rats treated with N-Hexacosanol (2 mg/kg and 8 mg/kg i.p. every day). Although N-Hexacosanol failed to modify the diabetic status, increases in serum creatinine as well as in kidney weight were significantly reduced. The malonaldehyde and transforming growth factor beta-1 (TGF-β1) concentrations as well as the protein kinase C (PKC) activities in the diabetic kidney were significantly higher than those of the control, which were decreased by treatment with N-Hexacosanol. Histological examinations revealed that N-Hexacosanol significantly ameliorated diabetic-induced tubulointerstitial pathological changes. Our data suggest that N-Hexacosanol could prevent increases in the malonaldehyde and TGF-β1 concentrations and PKC activities in the kidney, and ameliorate diabetic-induced nephropathy.
-
Treatment with cyclohexenonic long-chain fatty alcohol reverses diabetes-induced tracheal dysfunction in the rat.
Pharmacology, 2006Co-Authors: Takuya Hanada, Motoaki Saito, Susumu KanzakiAbstract:In this study, we tried to elucidate the effect of cyclohexenonic long-chain fatty alcohol (N-Hexacosanol) on tracheal dysfunction in diabetic rats. Diabetes was induced in 8-week-old male Sprague-Dawley rats by administering an intraperitoneal injection of 50 mg/kg streptozotocin. Non-diabetic control rats received an injection of citrate-phosphate buffer alone. Four weeks after the induction of diabetes, rats were randomly divided into 5 groups: age-matched non-diabetic control rats (group A); 4-week diabetic rats without N-Hexacosanol treatment (group B); diabetic rats treated with vehicle (group C), and diabetic rats treated with N-Hexacosanol at a dose of 2 or 8 mg/kg i.p. every day for the following 4 weeks (group D and group E, respectively; n = 6–8 animals in each group). Serum glucose and insulin levels were determined, as were the contractile responses induced by carbachol and 100 mmol/l KCl. The participation of M2 and M3 receptors was investigated in the trachea by real-time polymerase chain reaction (PCR), hematoxylin and eosin (HE) and immunohistochemical staining. Hypertrophy of airway smooth muscle was observed in diabetic rats, and was ameliorated by treatment with N-Hexacosanol. Treatment with either 2 or 8 mg/kg N-Hexacosanol did not alter diabetic rat status, i.e., body weight, serum glucose or serum insulin levels, but it significantly reversed the decrease in tracheal wall thickness and diabetes-induced hypercontractility in the rat trachea. In the immunohistochemical studies, muscarinic M2 and M3 receptors were expressed in the airway smooth muscle, the elastic fibers, the fibroblast and the surface of epithelium, and these expressions were not altered by either induction of diabetes or N-Hexacosanol treatment. The expression of M3 muscarinic receptor mRNAs in the trachea tended to be increased by the induction of diabetes and normalized when treated with N-Hexacosanol. Our data indicate that N-Hexacosanol could reverse diabetes-induced hypercontractility in the rat trachea.