Işıl Öcal

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.

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.

Effects of alternating magnetic field on the metabolism of the healthy and diabetic organisms

The aim of this study was to determine the effects of alternating magnetic field on the metabolism of the healthy and diabetic rats. The rats were divided into two experimental groups. Magnetic fields of 5 and 8mT intensity was applied to the first group of rats for 3 weeks (C5mT, CMF5mT, C8mT and CMF8mT). The second group was identified as diabetics group and 5mT was applied (D5mT and DMF5mT). The control groups (C5mT, C8mT, D5mT) of applied magnetic fields were placed in the same cage of the rats in experimental groups that have the same conditions but no pass current. The weights of rats exposed to magnetic fields in experimental groups were increased to initial weight; the plasma glucose levels were decreased in the blood parameters of the healthy and diabetic rats that they were exposed to 5mT and 8mT intensity magnetic fields. The decrease of the level of the total cholesterol and triglyceride in the blood plasma of the rats, showed that magnetic fields affected the hormonal systems, directly or indirectly, and slowed down the metabolism or hidratation.

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

Abstract 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 (Ca2+)-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 Ca2+ -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 Ca2+-free solutions.

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

Our aim 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. Forty rats (Wistar albino spp) weighing between 250-300 g were used. The rats were first divided into four groups. The first group was made up of the control rats (C, n=10), the second group was comprised of rats described as control+magnetic field group (C+MA, n=10), third group contained experimental diabetic rats (DIA, n=10), and the fourth group was comprised of both experimental diabetic and magnetic field group (DIA+MA, n=10). 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. The rats were weighed once every week during the one-month period. The measurements were expressed in grams. After the one-month study period, rats were killed by decapitation and the thoracic aorta dissected, and excess fats or connective tissues removed. Each ring was prepared with length 3-4 mm. Two stainless steel hooks were inserted into the lumen of the isolated blood vessel; one was fixed and the other connected to a force-displacement transducer (GrassFT03). Rings were prepared under a resting tension of 2 g after 2 hours in Krebs solution. The organ bath medium was maintained at 37/spl plusmn/0.1/spl deg/C and aerated with 95% O/sub 2/+5% CO/sub 2/ previously. Isometric tension measurements were recorded with the model 7 polygraph. We used phenylephrine for contraction responses and acetylcholine or sodium nitropruside for relaxation responses. The contractions were calculated in grams, and the relaxations expressed as percentage peak reduction of phenylephrine contracture. We observed attenuated contraction responses to PE and elevated relaxation responses to 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 nitroprusside 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 were decreased.

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.

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.