Investigation of the role of KATP channels in the cytotoxic effect of cypermethrin on rat-derived aortic smooth muscle cells.

We investigate role of ATP sensitive potassium (KATP) channel in cytotoxic effect of cypermethrin on rat aortic smooth muscle cells. Cytotoxicity analysis was performed at 0, 0.1, 0.5, 10, 50, and 100 µM concentrations of cypermethrin and the cell index (CI) was calculated. KATP currents were recorded using patch clamp technique for 50 and 100 µM concentrations and channel conductivity was determined by obtaining current-voltage characteristics. No cytotoxic effect was observed in the first 72 hours. At the 96th hour, only at 100 µM concentration, the CI value decreased significantly compared to control group and at 120 and 144th hours, it was observed that the CI value decreased significantly at all concentrations. Currents and conductivities were significantly decreased at 50 and 100 µM concentrations. Results gave clues that cypermethrin causes a cytotoxic effect on vascular smooth muscles and that KATP channels may have a role in the emergence of this effect.

Effect of imipramine on ether à-go-go potassium channel (Kv1.10) expression in DU145 prostate cancer cells.

In recent studies, it has been reported that ion channels play an important role in cancer formation. Therefore, it is possible that the use of pharmacological agents targeting ion channels will allow the development of new strategies for cancer treatment. In this study, we investigate the effect of imipramine on Eag1 channel expression in DU145 prostate cancer cells. Culture cells were divided into 4 groups as the control, 10, 50 and 75 µM imipramine. Eag1 channel currents and conductivity were determined by whole-cell patch-clamp technique and gene expression by real time-polymerase chain reaction (RT-PCR). Current records were taken before (at 0th minute, as control) and 10 min after imipramine administration to the cells. It was observed that all three doses of imipramine significantly reduced Eag1 currents and conductivity compared with the control. However, the differences between dose groups were not significant. Similarly, Eag1 channel protein expression was found to be significantly reduced for all three doses of imipramine compared with the control group, but there was no significant difference in gene expression between dose groups. Obtained results suggested that imipramine has the potential to be used as a pharmacological agent targeting the Eag1 channel in the treatment of prostate cancer.

Effect of Imipramine on radiosensitivity of Prostate Cancer: An In Vitro Study.

Prostate cancer is the most common cancer and leading cause of cancer death for males. Imipramine (IMI), which is a tricyclic antidepressant, has also been shown to has antineoplastic effect. This study was performed to investigate the radiosensitizing effect of IMI on DU145 prostate cancer cell. Cells were divided into 4 groups. Cell index, apoptotic activity, cell cycle arrest, oxidative stress and EAG1 channel currents were determined in all groups. Our findings showed that combined treatment with IMI and radiotherapy (RAD) did not enhance radiosensitivity of DU145 cells but as unexpected finding, treatment of IMI alone was more effective in DU145 cells.

Effect of low-level 1800 MHz radiofrequency radiation on the rat sciatic nerve and the protective role of paricalcitol.

The nervous system is an important target of radiofrequency (RF) radiation exposure since it is the excitable component that is potentially able to interact with electromagnetic fields. The present study was designed to investigate the effects of 1,800 MHz RF radiation and the protective role of paricalcitol on the rat sciatic nerve. Rats were divided into four groups as control, paricalcitol, RF, and RF + paricalcitol. In RF groups, the rats were exposed to 1,800 MHz RF for 1 h per day for 4 weeks. Control and paricalcitol rats were kept under the same conditions without RF application. In paricalcitol groups, the rats were given 0.2 µg/kg/day paricalcitol, three times per week for 4 weeks. Amplitude and latency of nerve compound action potentials, catalase activities, malondialdehyde (MDA) levels, and ultrastructural changes of sciatic nerve were evaluated. In the RF group, a significant reduction in amplitude, prolongation in latency, an increase in the MDA level, and an increase in catalase activity and degeneration in the myelinated nerve fibers were observed. The electrophysiological and histological findings were consistent with neuropathy, and the neuropathic changes were partially ameliorated with paricalcitol administration. Bioelectromagnetics. 39:631-643, 2018. © 2018 Wiley Periodicals, Inc.

N-Acetylcysteine-induced vasodilatation is modulated by KATP channels, Na+/K+-ATPase activity and intracellular calcium concentration: An in vitro study.

BACKGROUND: In this study, we aimed to investigate the role of ATP-sensitive potassium (KATP) channel, Na+/K+-ATPase activity, and intracellular calcium levels on the vasodilatory effect of N-acetylcysteine (NAC) in thoracic aorta by using electrophysiological and molecular techniques. METHODS: Rat thoracic aorta ring preparations and cultured thoracic aorta cells were divided into four groups as control, 2mM NAC, 5mM NAC, and 10mM NAC. Thoracic aorta rings were isolated from rats for measurements of relaxation responses and Na+/K+-ATPase activity. In the cultured thoracic aorta cells, we measured the currents of KATP channel, the concentration of intracellular calcium and mRNA expression level of KATP channel subunits (KCNJ8, KCNJ11, ABCC8 and ABCC9). RESULTS: The relaxation rate significantly increased in all NAC groups compared to control. Similarly, Na+/K+- ATPase activity also significantly decreased in NAC groups. Outward KATP channel current significantly increased in all NAC groups compared to the control group. Intracellular calcium concentration decreased significantly in all groups with compared control. mRNA expression level of ABCC8 subunit significantly increased in all NAC groups compared to the control group. Pearson correlation analysis showed that relaxation rate was significantly associated with KATP current, intracellular calcium concentration, Na+/K+-ATPase activity and mRNA expression level of ABCC8 subunit. CONCLUSION: Our findings suggest that NAC relaxes vascular smooth muscle cells through a direct effect on KATP channels, by increasing outward K+ flux, partly by increasing mRNA expression of KATP subunit ABCC8, by decreasing in intracellular calcium and by decreasing in Na+/K+-ATPase activity.

Electrophysiological, biochemical and ultrastructural effects of radiotherapy on normal rat sciatic nerve.

UNLABELLED: Abstract Purpose: The aim of the present study was to evaluate the electrophysiological, biochemical and ultrastructural changes on the rat sciatic nerve after radiotherapy. MATERIAL AND METHODS: Thirty male Wistar albino rats were divided into three groups as: Control group (n = 10), Group I: 3 months after radiotherapy (n = 10), and Group II: 6 months after radiotherapy (n = 10). Groups I and II were irradiated with a (60)Co gamma source. A dose of 20 Gy in 10 fractions was applied to Groups I and II. Compound motor action potentials (CMAP) were recorded in all groups. Superoxide dismutase (SOD) and catalase (CAT) activities and malondialdehyde (MDA) levels were measured in the sciatic nerve of rats using the biochemical methods. Ultrastructural changes were determined by electron microscopy. RESULTS: In Groups I and II, the amplitude of CMAP was significantly lower and the latency was significantly higher than that of the control group. There were no significant differences between Groups I and II regarding the CMAP amplitude and latency. The MDA levels were significantly increased, whereas the SOD and CAT activities were significantly decreased in experimental groups when compared with the control group. However, there were no significant changes in these parameters between Groups I and II. Degeneration in myelinated nerve fibers was observed ultrastructurally only in the experimental groups. Significant changes were observed between the control group and experimental groups in terms of ultrastructural myelin grading score and axonal damage score. No significant differences were found between Groups I and II. CONCLUSIONS: These findings indicated that the dose of 20 Gy in 10 fractions radiotherapy caused neuropathic damages in normal rat sciatic nerve 3 and 6 months after irradiation.

Exposure to gamma rays induces early alterations in skin in rodents: Mechanical, biochemical and structural responses.

In this study, the effect of gamma rays has been investigated on the normal rat skin using biomechanical, biochemical and histological techniques. Seventeen male Wistar albino rats were divided into two groups (control (n=7) and irradiated (n=10)). The irradiated group was treated with a (60)Co gamma source at a dose of 10Gy at room temperature. Skin biomechanics were measured with tensile test using biomaterial testing machine and maximum load, stiffness, energy absorption capacity, ultimate stress, ultimate strain and elastic modulus were calculated. In the irradiated group, energy, strain and toughness were significantly lower than in the control group (p<0.05). However, strength, displacement, stiffness, stress and elastic modulus were similar to that of the control group (p>0.05). Catalase (CAT) activities and the levels of malondialdehyde (MDA) in the skin of rats were measured using the biochemical methods. MDA levels significantly increased whereas CAT activities decreased in the irradiated group as compared with the control group (p<0.05). Diameters of collagen fibers were measured by transmission electron microscopy. There was no significant difference (p>0.05) between control and irradiated groups for collagen fiber diameter. Thickness of epidermis was significantly lower than the control group. There were no changes in the epidermis between the irradiated group and the control group ultrastructurally. The results of this study show that the gamma irradiation has a significant effect on normal healthy skin.