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Sciatic nerves of rats in each group. (A and H, Control group, showing normal sciatic nerve; B and I, Mod group, showing DPN sciatic nerve; C and J, MCB group, showing sciatic nerve of DPN rats treated with Mecobalamin; D-F and K-M, LTBK, MTBK and HTBK group, showing sciatic nerve of DPN rats treated with LTBK, MTBK and HTBK, respectively. Magnification, 400 ×).
Source publication
Tang Bi Kang (TBK) is a traditional Chinese medicine granule. It has been shown to have effects on nerve conduction velocity deficits, blood-related factors and oxidative stress. This study was undertaken to evaluate proposed antioxidative and anti-inflammatory activity of Tang Bi Kang in rats with diabetic peripheral neuropathy (DPN).
DPN was indu...
Contexts in source publication
Context 1
... staining of sciatic nerve showed normal structure in control group ( Figure 5A and H) and mild atrophy of axons and diffused structure of myelinated fibers at different density and size as well as demyelination in Mod group ( Figure 5 B and I). The morphological change of sciatic nerve morphology in the TBK-treated rats ( Figure 5 D-F and K-M) was smaller than that in Mod group. ...
Context 2
... staining of sciatic nerve showed normal structure in control group ( Figure 5A and H) and mild atrophy of axons and diffused structure of myelinated fibers at different density and size as well as demyelination in Mod group ( Figure 5 B and I). The morphological change of sciatic nerve morphology in the TBK-treated rats ( Figure 5 D-F and K-M) was smaller than that in Mod group. ...
Context 3
... staining of sciatic nerve showed normal structure in control group ( Figure 5A and H) and mild atrophy of axons and diffused structure of myelinated fibers at different density and size as well as demyelination in Mod group ( Figure 5 B and I). The morphological change of sciatic nerve morphology in the TBK-treated rats ( Figure 5 D-F and K-M) was smaller than that in Mod group. ...
Similar publications
Objective
To investigate the role of dexmedetomidine (DEX) in the inhibition of diabetic peripheral neuropathy (DPN) and the protection in the nerve damage.
Methods
Eighty male Sprague-Dawley (SD) rats were randomly allocated to four groups: the control group (C group), DPN model group (DPN group), DEX-treated group (DEX group), and the yohimbine...
Citations
... Tissues that had been fixed in paraffin were serially cut into 5 µm slices. To assess the degree of neuronal injury and the state of demyelination, sciatic nerve slices were stained with of hematoxylin and eosin and Luxol fast blue (LFB) from Alpha chemical group company, Egypt, respectively [25]. The amount of demyelina-Brain Sci. ...
Objective: We investigated the effect of L-carnitine (LC) on cuprizone (Cup) demyelinating rat model and its possible underlying mechanisms. Methods: Thirty male Sprague–Dawley (SD) rats were randomly allocated to three groups: the normal control group; the Cup group, in which Cup was administrated at a dose of 450 mg/kg per day orally via gastric gavage for 5 weeks; and the Cup + LC group, which received the same dose of Cup as the Cup group, except that the rats were treated additionally with LC 100 mg/kg/day orally for 5 weeks. The nerve conduction (NCV) in isolated sciatic nerves was measured; then, the sciatic nerves were isolated for H&E staining and electron microscope examination. The expression of myelin basic protein (MBP), IL-1β, p53, iNOS, and NF-KB by immunohistochemistry was detected in the isolated nerves. A PCR assay was also performed to detect the expression of antioxidant genes Nrf2 and HO-1. In addition, the level of IL-17 was measured by ELISA. Results: There was a significant reduction in NCV in the Cup group compared to normal rats (p < 0.001), which was significantly improved in the LC group (p < 0.001). EM and histopathological examination revealed significant demyelination and deterioration of the sciatic nerve fibers, with significant improvement in the LC group. The level of IL-17 as well as the expression of IL-1β, p53, iNOS, and NF-KB were significantly increased, with significant reduction expression of MBP in the sciatic nerves (p < 0.01), and LC treatment significantly improved the studied parameters (p < 0.01). Conclusion: The current study demonstrates a neuroprotective effect of LC in a Cup-induced demyelinating rat model. This effect might be due to its anti-inflammatory and antioxidant actions.
... Tissues that had been fixed in paraffin were serially cut into 5 µm slices. To assess the degree of neuronal injury and the state of myelination, sciatic nerve slices were stained with hematoxylin & eosin and Luxol fast blue (LFB) [20]. ...
Objective: To investigate the effect of vanillic acid (VA) on a Cuprizone (Cup) demyelinating rat model and the mechanisms behind such effect. Methods: Thirty adult male Sprague Dawley (SD) rats were randomly divided into three groups: control, Cuprizone, and VA groups. Cuprizone was administrated at a dose of 450 mg/kg per day orally via gastric gavage for 5 weeks. The nerve conduction velocity (NCV) was studied in an isolated sciatic nerve, and then the sciatic nerve was isolated for histopathological examination, electron microscope examination, immunohistochemical staining, and biochemical and PCR assay. The level of IL17 was detected using ELISA, while the antioxidant genes Nrf2, HO-1 expression at the level of mRNA, expression of the myelin basic protein (MBP), interferon-gamma factor (INF)-γ and tumor necrosis factor (TNF)-α, and apoptotic marker (caspase-3) were measured using immunohistochemistry in the sciatic nerve. Results: There was a significant reduction in NCV in Cup compared to normal rats (p < 0.001), which was markedly improved in the VA group (p < 0.001). EM and histopathological examination revealed significant demyelination and deterioration of the sciatic nerve fibers with significant improvement in the VA group. The level of IL17 as well as the expression of INF-γ and caspase-3 were significantly increased with a significant reduction in the expression of MBP, Nrf2, and HO-1 in the sciatic nerve (p < 0.01), and VA treatment significantly improved the studied parameters (p < 0.01). Conclusion: The current study demonstrated a neuroprotective effect for VA against the Cup-induced demyelinating rat model. This effect might be precipitated by the inhibition of inflammation, oxidative stress, and apoptosis.
... In the continuation of the same study, it was observed that some nerve fibers in the sciatic nerve appeared unmyelinated, and there were visible signs of axonal atrophy (Shi et al. 2013). Another study reported that while the sciatic nerve HE staining had a normal histological structure in the control group, atrophy in the axons, myelinated fibers of different densities and sizes, and demyelination were observed in the DNP group (Yang et al. 2015). Our study determined that the number of axons in the sciatic nerves of rats in the DNP group was significantly decreased compared to the control group. ...
Diabetic neuropathy (DNP) is a severe complication of diabetes mellitus. In this study, we examined the potential of hesperidin (HES) to attenuate DNP and the involvement of the TRPM2 channel in this process. The rats were given a single dose of 45 mg/kg of streptozotocin (STZ) intraperitoneally to induce diabetic neuropathic pain. On the third day, we confirmed the development of diabetes in the DNP and DNP + HES groups. The HES groups were treated with 100 mg/kg and intragastric gavage daily for 14 days. The results showed that treatment with HES in diabetic rats decreased STZ-induced hyperglycemia and thermal hyperalgesia. Furthermore, in the histopathological examination of the sciatic nerve, HES treatment reduced STZ-induced damage. The immunohistochemical analysis also determined that STZ-induced increased TRPM2 channel, type-4 collagen, and fibrinogen immunoactivity decreased with HES treatment. In addition, we investigated the TRPM2 channel activation in the sciatic nerve damage mechanism of DNP model rats created by STZ application using the ELISA method. We determined the regulatory effect of HES on increased ROS, and PARP1 and TRPM2 channel activation in the sciatic nerves of DNP model rats. These findings indicated that hesperidin treatment could attenuate diabetes-induced DNP by reducing TRPM2 channel activation.
... Vacuolisation and axonal degeneration were scored from 1 to 4 (1: minimal, 2: mild, 3: moderate, 4: severe). Nuclei and axons per area (mm 2 ) were assessed via ImageJ software, National Institutes of Health (NIH) [18]. ...
Purpose
There is still no widely-accepted local agent proven to be effective in nerve regeneration. We aimed to investigate the effects of chitosan gel and platelet-rich plasma
Materials and methods
Electrophysiological measurements were performed before and immediately after injury. The injured nerves were covered with spongostan impregnated with the following agents: Group 1 (Control Group): Saline at a dose of 50 µl; Group 2: Chitosan (CHT) at a dose of 50 µl; Group 3: PRP at a dose of 50 ml; and Group 4: a solution of CHT with PRP (1:1). The final measurements were performed after 3 weeks and the injured nerve of each rat was removed.
Results
There were statistically-significant differences between the groups regarding the measurements of the after-treatment values of stimulus threshold (p < 0.05). The best improvement in electrophysiological measurement and histopathological evaluation was found in Group 4 (CHT-PRP).
Conclusion
Chitosan gel has a positive effect on nerve healing and applying it along with PRP can enhance the effect of chitosan.
... [9][10][11] The upregulation of inflammatory cytokines has been reported in various types of diabetes and plays a vital role in the structural and functional damage of the peripheral nerves, leading to DN. [12][13][14] Oxidative stress and inflammation have been shown to be involved in the pathogenesis of DN, and these are considered important therapeutic targets. [15] Currently, aldose reductase inhibitors, ubiquinone (Coenzyme Q10, vitamin B12, and tricyclic antidepressants are used as the therapeutic agents for DN. However, they only provide symptomatic relief,there are very few approved effective therapies for painful or insensate DN. [16][17][18] The underlying etiology of DN is multifactorial, and multiple pathways are associated with its onset. ...
Diabetic neuropathy (DN) is one of the major complications of diabetes. However, there are few approved effective therapies for painful or insensate DN. Recent studies have implicated oxidative stress and inflammation in the pathogenesis of DN, and suppressing these could be an important therapeutic strategy. We previously reported that Stachybotrys microspora triprenyl phenol‐44D (SMTP‐44D) exhibits both antioxidant and anti‐inflammatory activities. The aim of this study was to evaluate the effects of SMTP‐44D in a mouse model of streptozotocin‐induced DN. SMTP‐44D was administered for 3 weeks after the disease induction, and its effects were evaluated on the basis of mechanical and thermal thresholds, blood flow in the bilateral hind paw, and blood flow and conduction velocity in the sciatic nerve. Furthermore, the levels of inflammatory factors, such as tumor necrosis factor (TNF)‐α, interleukin (IL)‐1β, IL‐6 and malondialdehyde (MDA), in the sciatic nerve were assessed. Neurological degeneration was assessed by measuring myelin thickness and g‐ratio in the sciatic nerve. SMTP‐44D treatment significantly improved allodynia, hyperalgesia, blood flow, and conduction velocity in DN model mice in a dose‐dependent manner. Neurological degeneration was also significantly improved, accompanied by decreased levels of inflammatory factors (TNF‐α, 57.8%; IL‐1β, 51.4%; IL‐6, 62.8%; and MDA, 40.7% reduction rate against the diabetes mellitus + normal saline group). Thus, SMTP‐44D can improve allodynia and hyperalgesia in DN without affecting the body weight and blood glucose levels, which may be due to its antioxidant and anti‐inflammatory properties. In conclusion, SMTP‐44D could be a potential therapeutic agent for the treatment of DN.
... 3.6. SP6616 treatment repressed inflammation in diabetic mice by inhibiting Kv2.1/NF-kB signaling SP6616 suppressed proinflammatory cytokines in the serum of diabetic mice-Given the tight association of inflammation with DPN pathology [49,50], we investigated the regulation of SP6616 treatment against inflammation in diabetic mice. ELISA assay results (Fig. 7a-f) indicated that the levels of proinflammatory cytokines TNF-a, IL-1b and IL-6 were downregulated in the serum of SP6616treated diabetic mice (STZ+SP6616, db/db+SP6616) compared with those of vehicle-treated diabetic mice (STZ, db/db). ...
Background
Diabetic peripheral neuropathy (DPN) is a common complication of diabetes severely afflicting the patients, while there is yet no effective medication against this disease. As Kv2.1 channel functions potently in regulating neurological disorders, the present work was to investigate the regulation of Kv2.1 channel against DPN-like pathology of DPN model mice by using selective Kv2.1 inhibitor SP6616 (ethyl 5-(3-ethoxy-4-methoxyphenyl)-2-(4-hydroxy-3-methoxybenzylidene)-7-methyl-3-oxo-2,3-dihydro-5H-[1,3]thiazolo[3,2-a]pyrimidine-6-carboxylate) as a probe.
Methods
STZ-induced type 1 diabetic mice with DPN (STZ mice) were defined at 12 weeks of age (4 weeks after STZ injection) through behavioral tests, and db/db (BKS Cg-m+/+Leprdb/J) type 2 diabetic mice with DPN (db/db mice) were at 18 weeks of age. SP6616 was administered daily via intraperitoneal injection for 4 weeks. The mechanisms underlying the amelioration of SP6616 on DPN-like pathology were investigated by RT-PCR, western blot and immunohistochemistry technical approaches against diabetic mice, and verified against the STZ mice with Kv2.1 knockdown in dorsal root ganglion (DRG) tissue by injection of adeno associated virus AAV9-Kv2.1-RNAi. Amelioration of SP6616 on the pathological behaviors of diabetic mice was assessed against tactile allodynia, thermal sensitivity and motor nerve conduction velocity (MNCV).
Findings
SP6616 treatment effectively ameliorated the threshold of mechanical stimuli, thermal sensitivity and MNCV of diabetic mice. Mechanism research results indicated that SP6616 suppressed Kv2.1 expression, increased the number of intraepidermal nerve fibers (IENFs), improved peripheral nerve structure and vascular function in DRG tissue. In addition, SP6616 improved mitochondrial dysfunction through Kv2.1/CaMKKβ/AMPK/PGC-1α pathway, repressed inflammatory response by inhibiting Kv2.1/NF-κB signaling and alleviated apoptosis of DRG neuron through Kv2.1-mediated regulation of Bcl-2 family proteins and Caspase-3 in diabetic mice.
Interpretation
Our work has highly supported the beneficial of Kv2.1 inhibition in ameliorating DPN-like pathology and highlighted the potential of SP6616 in the treatment of DPN.
Funding
Please see funding sources.
... These were formed as a result of necrosis of a part of the nerve tissue. The obtained results correlates with data of another group of scientist [51], therefore, the obtained images demonstrate DP development. ...
Ulcers and slow wound healing are common in diabetic polyneuropathy (DP), as well as shooting or burning pain, sensitivity to touch or lack of sensitivity, low oxygenation of nerve tissue, conductivity disorders and various vascular disorders. The mechanisms of DP development are complex and have not been completely studied. To take into account the role of B group vitamins, we investigated histological structure of nerve tissue, the level of different growth factors and the qualitative composition of active proteolytic enzymes in rats with DP and after the use of the metabolic drug Cocarnit for 9 days. This drug composition include nicotinamide, cocarboxylase, cyanocobalamin, adenosine triphosphate disodium trihydrate. We used an histological study of sciatic nerve; enzyme-linked immunosorbent assay and enzyme electrophoresis methods. In rats with DP, fragmentation of nerve tissue and their necrosis was established. Moreover, degraded forms of plasmin that has a fully functional serine proteinase domain are evident, and, therefore, it exhibits proteolytic properties. DP led to a decrease of neuron growth factor (NGF), vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). After treatment, the histological structure of nerve tissue was significantly improved, and the expression of growth factors NGF and bFGF was increased. Our study demonstrated that administration of Corcarnit brought about the complete restoration of the activation potential of plasmin and the almost disappearance of all degraded forms which were evident in the group with DP.
... GSH-Px catalyzed the reduction of GSH in the presence of hydrogen peroxide. One unit of enzyme activity represents a decrease in GSH concentration of 1 mm/ml of serum (Yang et al., 2015). ...
Objective
To investigate the role of dexmedetomidine (DEX) in the inhibition of diabetic peripheral neuropathy (DPN) and the protection in the nerve damage.
Methods
Eighty male Sprague-Dawley (SD) rats were randomly allocated to four groups: the control group (C group), DPN model group (DPN group), DEX-treated group (DEX group), and the yohimbine treated group (YOH group). DPN was induced by intraperitoneal administration of streptozocin (STZ) (35 mg/kg). The body weights, blood glucose level, mechanical withdrawal threshold (MWT), thermal withdrawal latency (TWL), the motor, and sensory nerve conduction velocities (MNCV and SNCV) of sciatic nerve were measured. Then the sciatic nerve was isolated for H&E staining and immunohistochemical staining. The oxidative stress makers such as malondialdehyde (MDA), superoxide-dismutase (SOD), and glutathione peroxidase (GSH-Px) and apoptosis related cytokines such as Bax, Bcl-2, and caspase-3 were estimated.
Results
There was no significant difference of the blood glucose and body weight among the DPN group, DEX group, and YOH group. H&E staining showed that DEX treatment can ameliorate the damage of sciatic nerve cells. In the DPN group, MWT, TWL, MNCV, and SNCV were significantly reduced compared with the C group (P < 0.05). In DEX group rats, MWT, TWL, MNCV, and SNCV were increased significantly (P < 0.05) compared with the DPN group and YOH group rats. Lower SOD and GSH-Px, and higher MDA were found in the DPN group compared with the C group (P < 0.01), and DEX treatment restored SOD, GSH-px, and MDA activity significantly (P < 0.01). The expression levels of Bax and caspase-3 were increased, while that of Bcl-2 was decreased significantly in the DPN group compared with the C group (P < 0.05). In the DEX group, the expression levels of Bax and caspase-3 were decreased significantly (P < 0.05), while that of Bcl-2 was increased significantly (P < 0.05) compared with the DPN group and the YOH group.
Conclusion
The results of this study demonstrated that DEX has the inhibitory and protective effects on DPN of rats. This may be associated with its antioxidative and anti-apoptosis responses.
... In this study, gliclazide significantly restored the antioxidant defense against acetic acid-induced colitis as demonstrated by the reduction of MDA, concurrently with the restoration of GSH and SOD. These findings are consistent with the previously reported antioxidants properties of gliclazide (Yang et al., 2015;Araujo et al., 2019) and support the postulation of the involvement of the antioxidant properties of gliclazide in the mitigation of acetic acid-induced colitis. ...
Ulcerative Colitis is a universal autoimmune disease with high incidence rates worldwide. It is characterized by the existence of many other concurrent immune-associated ailments, including diabetes. The used strategies for the management of this highly costing and complicated disease face great challenges. Therefore, the urge for new medication with fewer side effects and high efficacy is growing. The peroxisome proliferator-activated receptor-gamma (PPARγ) and nuclear factor Kappa-B (NF-κB) can be considered as crucial targets for the treatment of ulcerative colitis. Several studies reported the antioxidants, anti-inflammatory, and antiapoptotic actions of gliclazide and evaluated its cardioprotective and renoprotective effects. However, its impact on ulcerative colitis has never been investigated. This study delineated the effect of gliclazide administration on ulcerative colitis induced by acetic acid in rats and the underlying molecular mechanisms. Gliclazide (10 mg/kg; p.o) prominently decreased colon tissue injury as assessed by the histopathological analysis, myeloperoxidase, and intercellular adhesion molecule-1 levels. Gliclazide significantly alleviated the proinflammatory mediator, IL-6, promoted the anti-inflammatory cytokine, IL-10 and, withheld oxidative stress in the injured colon tissues. The protective effect of gliclazide was mediated through the upregulation of PPARγ and downregulation of NF-κB expression. The diminution of ulcerative colitis was also accompanied by an inhibition of the elevated activity and expression of mitogen-activated protein kinases and caspase-3 as assessed by Western blot and immunohistochemistry, respectively. Our findings spotlight, for the first time, the potential of the antidiabetic agent, gliclazide, to attenuate the experimentally induced ulcerative colitis. Therefore, gliclazide might be a propitious agent for the management of ulcerative colitis in diabetic patients.
... These results were consistent with previous studies, wherein hyperalgesia has been reported after 6, 8, and 12 weeks of hyperglycemia. [19][20][21] Many studies, however, have still reported hypoalgesia. For example, Davidson et al. found that STZ-induced diabetic rats displayed thermal hypoalgesia after 16 weeks of untreated diabetes, and the high-fat-fed/low-dose STZ-induced diabetic rats showed thermal hypoalgesia after 8 weeks of a high fat diet and 16 weeks of hyperglycemia induced by STZ, 22,23 whereas Stavniichuk et al. reported that STZ-induced diabetic C57Bl6/J mice exhibited thermal hypoalgesia but tactile allodynia. ...
Scope:
Maltol (3-hydroxy-2-methy-4-pyrone), a potent antioxidative agent, typically is used to enhance flavor and preserve food. This study evaluated its effects on preventing diabetic peripheral neuropathy (DPN) in streptozotocin (STZ)-induced diabetic rats and explored its mechanisms.
Methods and results:
We intraperitoneally injected Sprague-Dawley (SD) rats with STZ (65 mg kg-1, ip) and treated the rats with different doses of maltol after 4 weeks of injection. During treatment, we evaluated motor nerve conduction velocity (MNCV) and thermal and mechanical hyperalgesia and assayed the oxidative stress, Na+-K+-ATPase activity, and apoptosis. Repeated treatment with maltol for 12 weeks significantly improved thermal and mechanical hyperalgesia, increased the MNCV, elevated the Na+-K+-ATPase activity, and ameliorated oxidative stress and apoptosis in STZ-induced diabetic rats. We coincubated RSC96 cells, a Schwann cell line, with maltol and hydrogen peroxide (H2O2, 0.6 mM). Evidently, maltol increased cell viability and inhibited apoptosis after injury by H2O2.
Conclusions:
Maltol was demonstrated to prevent DPN development and may provide a new alternative for the treatment of DPN.
