Clinical, electrophysiological, and histomorphological effects of local coenzyme Q10 and vitamin E use in a rat model of peripheral nerve injury.

OBJECTIVE: This study aimed to investigate the clinical, electrophysiological, and histomorphological effects of local use of coenzyme Q10 and vitamin E combination in a rat model of peripheral nerve injury. METHODS: Forty adult female Wistar-Albino rats weighing 250-350 g were kept in a room with a temperature of 20-22°C and a light/dark cycle of 12 hours. They had free access to food and water. The right sciatic nerves of 40 rats were transected and repaired. Subjects were divided into 4 groups: controls (control-4 weeks and control-8 weeks) and treatments (treatment-4 weeks and treatment-8 weeks). A combination of coenzyme Q10 and vitamin E was applied to the repair site by a catheter placed subcutaneously in the treatment group. Only transection-repair was done in the control group. All groups were divided into 2 subgroups for histomorphological, clinical, and electrophysiological experiments because of concerns about possible interference with histomorphological preparation (5 rats in each group). The experiment results were examined by the thermal plantar test, action potential and latency time measurements, and electron microscopy at the end of 4 and 8 weeks. The intact group was studied as the uninterrupted 10 left sciatic nerves of control for 4 weeks. RESULTS: The mean thermal plantar test results of the intact group were better than those of the control groups (P < .05). However, there was no significant difference between the intact and treatment groups. In the histomorphological examination, the number of myelinated axons increased significantly, and the myelin structure was closer to that of the intact group, especially when the treatment-8 group was compared with the control groups (control-4: P < .0001, control-8: P < .01). CONCLUSION: Local use of coenzyme Q10 and vitamin E seems useful in the experimental rat sciatic nerve transection-repair model.

Effect of 40 Hz Magnetic Field Application in Posttraumatic Muscular Atrophy Development on Muscle Mass and Contractions in Rats.

Muscle atrophy refers to the deterioration of muscle tissue due to a long-term decrease in muscle function. In the present study, we simulated rectus femoris muscle atrophy experimentally and investigated the effect of pulsed electromagnetic field (PEMF) application on the atrophy development through muscle mass, maximal contraction force, and contraction-relaxation time. A quadriceps tendon rupture with a total tenotomy was created on the rats' hind limbs, inhibiting knee extension for 6 weeks, and this restriction of the movement led to the development of disuse atrophy, while the control group underwent no surgery. The operated and control groups were divided into subgroups according to PEMF application (1.5 mT for 45 days) or no PEMF. All groups were sacrificed after 6 weeks and had their entire rectus femoris removed. To measure the contraction force, the muscles were placed in an organ bath connected to a transducer. As a result of the atrophy, muscle mass and strength were reduced in the operated group, while no muscle mass loss was observed in the operated PEMF group. Furthermore, measurements of single, incomplete and full tetanic contraction force and contraction time (CT) did not change significantly in the operated group that received the PEMF application. The PEMF application prevented atrophy resulting from 6 weeks of immobility, according to the contraction parameters. The effects of PEMF on contraction force and CT provide a basis for further studies in which PEMF is investigated as a noninvasive therapy for disuse atrophy development. © 2022 Bioelectromagnetics Society.

The healing effect of pulsed magnetic field on burn wounds.

A burn is one of the most difficult injuries people can face.The primary pathology is coagulation necrosis resulting from tissue damage.Many wound care products have been developed to be used in situations such as the poor general condition of the patient and lack of solid area to be grafted. However, the high costs of these products make their use complicated.In this study, the effect of PEMF on cutaneous wound healing in an animal burn model was evaluated and the dose and duration of the magnetic field should be discussed for this effect to occur. Animals were divided into five groups including eight each (n = 40) (Groups 1, 2, 3, 4, 5).Group 1 was the control group; received no treatment after second-degree burn wound. Group 2 received daily wound care with saline. Group 3 received daily wound care with pomade containing mupirocin. Group 4 received Pulsed Electromagnetic Field signal for 60 min (1.5 m T and 40 Hz for seven days and Group 5 also received PEMF signal for 60 min the same frequency and intensity for14 days. Microscopically, second-degree burn wounds were successfully detected in all rats. Histopathological examination results in no significant difference between groups in neutrophil infiltration. The difference between the groups in vascularization was statistically significant between Group II and Group V (p < 0.001) and between Group I and Group V (p = 0.005) Epithelialization was present in 75% of the rats in Group V, while no epithelialization was observed in any of the other groups. In conclusion, we observed a significant improvement in the stasis zone of the group receiving Pulsed Electromagnetic Field for two weeks.

A Low-Frequency Pulsed Magnetic Field Reduces Neuropathic Pain by Regulating NaV1.8 and NaV1.9 Sodium Channels at the Transcriptional Level in Diabetic Rats.

Low-frequency pulsed magnetic field (LF-PMF) application is a non-invasive, easy, and inexpensive treatment method in pain management. However, the molecular mechanism underlying the effect of LF-PMF on pain is not fully understood. Considering the obvious dysregulations of gene expression observed in certain types of voltage-gated sodium channels (VGSCs) in pain conditions, the present study tested the hypothesis that LF-PMF shows its pain-relieving effect by regulating genes that code VGSCs proteins. Five experimental rat groups (Control, Streptozotocin-induced experimental painful diabetic neuropathy (PDN), PDN Sham, PDN 10 Hz PMF, and PDN 30 Hz PMF) were established. After the pain formation in PDN groups, the magnetic field groups were exposed to 10/30 Hz, 1.5 mT PMF for 4 weeks, an hour daily. Progression of pain was evaluated using behavioral pain tests during the entire experimental processes. After the end of PMF treatment, SCN9A (NaV1.7 ), SCN10A (NaV1.8 ), SCN11A (NaV1.9 ), and SCN3A (NaV1.3 ) gene expression level changes were determined by analyzing real-time polymerase chain reaction results. We found that 10 Hz PMF application was more effective than 30 Hz on pain management. In addition, NaV1.7 and NaV1.3 transcriptions were upregulated while NaV1.8 and NaV1.9 were downregulated in painful conditions. Notably, the downregulated expression of the genes encoding NaV1.8 and NaV1.9 were re-regulated and increased to control level by 10 Hz PMF application. Consequently, it may be deduced that 10 Hz PMF application reduces pain by modulating certain VGSCs at the transcriptional level. © 2021 Bioelectromagnetics Society.

Pulsed magnetic field maintains vascular homeostasis against H2O2-induced oxidative stress.

Pulsed magnetic fields (PMFs) have significant therapeutic effects on many disorders. However, the effects of PMF on vascular homeostasis remain unclear. Therefore, in the present study, we investigated the role of in vivo PMF in maintaining vascular homeostasis during H2O2-induced oxidative stress. For this purpose, rats were exposed to PMF (40 Hz, 1.5 mT) for 1 h for a period of 30 days, following which their thoracic aortas were excised. H2O2 was exogenously applied to the aortic rings. Constrictions were measured in a tissue bath using an electrophysiological technique. Bcl-2 and endothelial nitric oxide synthase (eNOS) protein levels were determined by Western blotting. We found lesser H2O2-induced vasoconstriction in the PMF group than in the control group in endothelium-intact (E+) rings. As H2O2 also induces apoptosis, after incubation with H2O2 (40 min) to induce early apoptosis, we added KCl and measured KCl-induced contractions. All the groups, endothelium intact or denuded (E-) showed decreased responses; however, we still observed the effect of PMF in the E+ group due to increased endothelial activity. In addition, PMF increased the expression of the eNOS protein, which might be a key target of PMF. Our results suggest that in vivo application of PMF protects vascular responses through endothelium-mediated mechanisms during oxidative stress. Therefore, PMF might play a protective role against vascular diseases.

Determining the effect of long-term dexamethasone and prednisolone treatment on sugammadex

Background/aim: We aimed to investigate the effect of long-term use of dexamethasone and prednisolone on the reversal effect of sugammadex. Materials and methods: TTwenty-four male Wistar albino rats were divided into three groups. Dexamethasone (600 µg/kg) was given to group D, prednisolone (10 mg/kg) was given to group P, and an equivalent volume of saline per day was administered intraperitoneally to group S for 14 days, respectively. The left hemidiaphragm with attached phrenic nerve was maintained in Krebs solution. Sugammadex (30 µmol/L) was applied while rocuronium (10 µmol/L) was present in an organ bath and a single twitch was obtained. The right hemidiaphragm was used for both adult ( ε-subunit) and fetal nicotinic acetylcholine receptor (AChR) ( ε-subunit) determination using polymerase chain reaction. Results: All animals lost weight, except group S. The mean baseline single-twitch tension was lower in both group D (14.4 ± 1.7 g) and group P (12.68 ± 0.05 g) than group S (16.8 ± 0.5 g) (P < 0.001). When sugammadex was added to the organ bath while rocuronium was present, the single twitch was measured to be lower in both group D (11.7 ± 0.7 g) and group P (11.5 ± 0.78 g) than group S (16.5 ± 0.24 g) (P < 0.001). Ɣ-AChR expression was higher in both dexamethasone and prednisolone than in saline. Conclusion: Long-term medication with dexamethasone and prednisolone caused muscle weakness, resistance to neuromuscular blockers, and upregulation of immature Ɣ-AChR and reduced the neuromuscular reversal effect of sugammadex.

ATP sensitive K+ channel subunits (Kir6.1, Kir6.2) are the candidate mediators regulating ameliorating effects of pulsed magnetic field on aortic contractility in diabetic rats.

Diabetes mellitus is a metabolic disease that causes increased morbidity and mortality in developed and developing countries. With recent advancements in technology, alternative treatment methods have begun to be investigated in the world. This study aims to evaluate the effect of pulsed magnetic field (PMF) on vascular complications and contractile activities of aortic rings along with Kir6.1 and Kir6.2 subunit expressions of ATP-sensitive potassium channels (KATP ) in aortas of controlled-diabetic and non-controlled diabetic rats. Controlled-diabetic and non-controlled diabetic adult male Wistar rats were exposed to PMF for a period of 6 weeks according to the PMF application protocol (1 h/day; intensity: 1.5 mT; consecutive frequency: 1, 10, 20, and 40 Hz). After PMF exposure, body weight and blood glucose levels were measured. Then, thoracic aorta tissue was extracted for relaxation-contraction and Kir6.1 and Kir6.2 expression experiments. Blood plasma glucose levels, body weight, and aortic ring contraction percentage decreased in controlled-diabetic rats but increased in non-controlled diabetic rats. PMF therapy repressed Kir6.1 mRNA expression in non-controlled diabetic rats but not in controlled diabetic rats. Conversely, Kir6.2 mRNA expressions were repressed both in controlled diabetic and non-controlled diabetic rats by PMF. Our findings suggest that the positive therapeutic effects of PMF may act through (KATP ) subunits and may frequently occur in insulin-free conditions. Bioelectromagnetics. 39:299-311, 2018. © 2018 Wiley Periodicals, Inc.

Pain-relieving effects of pulsed magnetic fields in a rat model of carrageenan-induced hindpaw inflammation.

PURPOSE: Many strategies have been investigated to exclude the several side-effects of pharmacological or invasive treatments. Non-invasive pulsed magnetic field (PMF) treatment with no toxicity or side-effects can be an alternative to pharmacologic treatments. The purpose of this study was, therefore, to investigate the pain-relieving effects of PMF treatment in the inflammatory pain conditions. MATERIALS AND METHODS: Effects of PMF treatment on the hallmarks of the inflammatory pain indices such as hyperalgesia, allodynia, edema and several biochemical parameters that evaluate oxidative stress were investigated using a well established carrageenan (CAR)-induced hindpaw inflammation model in rats. RESULTS: CAR injection lowered the paw withdrawal thermal latencies (hyperalgesia) and mechanical thresholds (allodynia). CAR also decreased the superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) levels and increased malondialdehyde (MDA) levels compared with healthy rat paw tissues. PMF treatment produced significant increases in the thermal latencies and mechanical thresholds in CAR-injected paws. In the inflamed paw tissues, PMF increased the activities of SOD, CAT and GPx and decreased MDA level. We also demonstrated that PMF decreased paw mass indicating that it has an anti-edematous potential. CONCLUSIONS: The present results reveal that PMF treatment can ameliorate the CAR-induced inflammatory pain indices such as mechanical allodynia, thermal hyperalgesia and edema, and attenuate the oxidative stress. The action mechanisms of PMF in CAR-induced inflammation might be related to the increases in the levels of antioxidant enzymes in inflamed tissues. The findings suggest that PMF treatment might be beneficial in inflammatory pain conditions.

Dexmedetomidine modifies uterine contractions in pregnancy terms of rats.

OBJECTIVES: The present study was aimed at determining the effective doses of Dexmedetomidine (Dex) involved in amplitude of contraction-force and frequency of uterine rings in pregnancy terms of rats. All experiments involving animal subjects were carried out with the approval of animal care and use Ethical Committee of Cukurova University. Experiments were performed on female Albino-Wistar rats (200-260 g; n = 40). MATERIALS AND METHODS: Uterine rings from pregnant rats were placed in organ bath with Krebs and calcium ion (Ca(2+))-free solutions to record and exposed to serially increasing log10 concentrations of Dex. RESULTS: In Krebs solution, while Dex caused an increase in the spontaneous contraction-forces in all pregnancy terms of rats in a significant dose-dependent manner, it led to a decrease in contraction-frequency in late-pregnancy term of rats. In Ca(2+)-free, the spontaneous contraction-force decreased in late-pregnancy term and increased in early and middle-pregnancy terms. In addition, while Dex increased the contraction-frequency in early and middle-pregnancy terms, it decreased in late-pregnancy term in a dose-dependent manner. STATISTICAL ANALYSIS USED: The data were subjected to one-way analysis of variance. Repeated measures were employed for comparison of several group means through the Tukey post-hoc test (SPSS 10.00 Inc., Chicago, Ill, USA). P < 0.05 was considered statistically significant. CONCLUSIONS: This study suggested that Dex might differently alter the spontaneous contraction-forces and contraction-frequencies of uterine rings in all pregnancy terms of rats in Krebs and Ca(2+)-free solutions.

Clodronate changes neurobiological effects of pulsed magnetic field on diabetic rats with peripheral neuropathy.

Several studies have reported that pulsed magnetic fields (PMFs) can be a choice of therapy for diabetic peripheral neuropathy. However, the exact underlying mechanism of PMF is still not known. The purpose of this study was, therefore, to investigate the effects of clodronate encapsulated with liposome, a specific agent depleting macrophage, on PMF-treated streptozotocin-induced type I diabetic rats with peripheral neuropathy. Effects of PMF, liposome-encapsulated clodronate (LEC) or their combined treatments were investigated in diabetic rats by measuring the thermal latencies, mechanical thresholds, whole blood glucose levels, serum insulin level, and body mass. In diabetic rats, PMF exhibited a decrease in the blood glucose levels but did not change the serum insulin level. Both mechanical thresholds and thermal latencies of diabetic rats enhanced throughout the PMF treatment. During the PMF treatment, the administration of LEC suppressed the PMF-induced decrease in blood glucose level, PMF-induced increase in mechanical threshold and thermal latencies in diabetic animals. In addition, PMF reduced the LEC-induced increase in insulin levels of diabetic rats. Findings demonstrated that although effects of both PMF alone and LEC alone on diabetic animals are mostly positive, LEC may remove the therapeutic efficacies of PMF in combined treatment.

Neurobiological effects of pulsed magnetic field on diabetes-induced neuropathy.

In the clinic, although several pharmacological agents or surgical procedures are used to treat diabetes and diabetes-induced neuropathic pain, their success has been limited. Therefore, development of different alternatives in treatments is very important. The purpose of this study was to determine the efficacy of pulsed magnetic field (PMF) in improving signs and symptoms of diabetic neuropathy. In this study, the effects of PMF treatment were investigated in Streptozotocin (STZ)-induced acute and chronic diabetic rats by measuring the thermal latencies, mechanical thresholds, whole blood glucose levels and body weights. After STZ administration to rats, blood glucose level elevated and body weight decreased. Although PMF treatment did not affect changes in body weight, the blood glucose levels of PMF-treated diabetic rats exhibited a decrease during the treatments. Diabetic animals displayed marked decrease in mechanical thresholds and thermal latencies. While treatment of PMF partially restored the mechanical thresholds and thermal latency in acute diabetic rats, PMF caused a corrective effect on only mechanical threshold of chronic diabetic rats. These results suggested that treatment of PMF can potentially ameliorate the painful symptoms of diabetes, such as hyperalgesia and allodynia, by partially preventing the hyperglycemia.

Macrophage depletion delays progression of neuropathic pain in diabetic animals.

Despite the fact that it is a frequent diabetic complication, the mechanisms underlying the manifestation of diabetic neuropathic pain remain poorly understood. In this study, we hypothesized that the depletion of peripheral macrophages with liposome-encapsulated clodronate (LEC) can prevent, at least delay, the progression of diabetes-induced neuropathic pain. Therefore, the aim of this study was to evaluate the effects of macrophage depletion on mechanical allodynia and thermal hyperalgesia in the streptozotocin (STZ)-induced rat model of diabetic neuropathy. LEC was intravenously administrated to rats three times with 5-day intervals. A single intravenous injection of STZ caused an increase in the average blood glucose levels and a decrease in body weight. Although LEC treatment did not affect the body weight gain, the blood glucose level was lower and serum insulin level higher in LEC-treated diabetic rats than in that of diabetic rats. In addition, LEC treatment alleviated the excessive damage in beta cells in diabetic rats. Diabetic animals displayed marked mechanical allodynia and thermal hyperalgesia. While the treatment of diabetic rats with LEC did not significantly change the thermal withdrawal latency, diabetes-induced decrease in mechanical paw withdrawal threshold was significantly corrected by the LEC treatment. The results of this study show that thermal hyperalgesia and mechanical allodynia induced by diabetes may be associated with alterations in blood glucose level. Depletion of macrophages with LEC in diabetic rats may reduce mechanical allodynia without affecting thermal hyperalgesia. Taken together, these results suggested that depletion of macrophages in diabetes may partially postpone the development of diabetic neuropathic pain.

The effects of chronic AC magnetic field on contraction and relaxation of isolated thoracic aorta rings of healthy and diabetic rats

The aim of in this study was to determine the effect of chronic alternating current (AC) magnetic field on the contraction and relaxation parameters of isolated thoracic aorta rings in healthy and diabetic rats. Sixty rats (Wistar albino spp) weighing between 250-300 g were used. The rats were divided into four groups: 1-Control (C), 2- control + magnetic field (C+MA), 3- experimental diabetic (DIA), 4- experimental diabetic and magnetic field (DIA+MA). Magnetic fields of 5 mT intensity and 50 Hz frequency oriented in the north-south direction was applied to the C+MA and DIA+MA groups for 2 hours each day for one month, after which rats were killed by decapitation and the thoracic aorta dissected. This showed attenuated contraction responses to phenylephrine (PE) and elevated relaxation responses to acetylcholine (ACh) of the thoracic aorta rings of rats in the C+MA and DIA+MA groups compared to group C but no changes in the relaxation responses to sodium nitroprruside (SNP) of thoracic aorta rings relative to group C and DIA. The weights of rats in DIA+MA or C+MA groups compared to the DIA and C groups decreased.