The effect of 6GHz radiofrequency electromagnetic radiation on rat pain perception.

This paper presents data on pain perception in rats exposed to 6 GHz radiofrequency electromagnetic radiation (RF-EMR). Rats were divided into two groups: control (n = 10, 4 replicates per test) and RF-EMR exposed group (n = 10, 4 replicates per test). Nociceptive responses of the groups were measured using rodent analgesiometry. Rats were divided into control and RF-EMR exposed groups. Nociceptive responses were measured using rodent analgesiometry. RF-EMR exposed rats had a 15% delay in responding to hot plate thermal stimulation compared to unexposed rats. The delay in responding to radiant heat thermal stimulation was 21%. We determined that RF-EMR promoted the occurrence of pressure pain as statistical significance by + 42% (p < 0.001). We observed that RF-EMR exposure increased nociceptive pain by + 35% by promoting cold plate stimulation (p < 0.05). RF-EMR exposure did not affect thermal preference as statistical significance but did support the formation of pressure pain perception.

In this study, we present data on pain perception in rats exposed to 6GHz RF-EMR. RF-EMR exposed rats showed delayed responses to hot plate and radiant heat thermal stimulation. RF-EMR increased pressure and nociceptive pain as statistically significance. In particular, the effects of RF-EMR should be considered when assessing hyperalgesic and hypoalgesic symptoms in the clinic. The results of this study indicate the need to take precautions against the possible negative effects of RF-EMR on human health with the rise of 5G technology.

Effects of high-molecular-weight polyvinyl chloride on Xenopus laevis adults and embryos: the mRNA expression profiles of Myf5, Esr1, Bmp4, Pax6, and Hsp70 genes during early embryonic development.

Microplastics and associated adverse effects have been on the global agenda in recent years. Because of its importance as a model organism for studies on developmental biology, Xenopus laevis has been chosen as the study animal in in vitro teratogenesis studies. FETAX test uses early-stage embryos of X. laevis to measure the potential of substances to cause mortality, malformation, and growth inhibition in developing embryos. The aim of this study was to examine the effects of high molecular weight polyvinyl chloride (HMW-PVC) on parental X. laevis frogs and their embryos using the FETAX test. To this purpose, a HMW-PVC dose of 1% of body weight/twice each week was provided to frogs by oral gavage throughout 6 weeks. After the procedure, oocytes and sperms of HMW-PVC-exposed frogs were fertilized and FETAX was applied to selected embryos. After the completion of a 96-h incubation period, tadpoles were examined, their live/dead status were determined, their lengths were measured, and their anomalies were photographed. Besides, excised organs of the parental frogs were referred to histopathology examination. On the other hand, the mRNA expression levels of Hsp70, Myf5, Bmp4, Pax6, and Esr1 genes were determined by applying real-time quantitative PCR method to cDNA which was synthesized from the total RNA of embryos. The results showed that treatment with HMW-PVC dose of 1% of body weight/twice each week caused malformations and decreased viability. Hsp70 and Pax6 gene expression levels significantly decreased in all assay groups, as compared with controls. Lung and intestine tissues showed normal appearance in histopatological examination. Further research is required to explain the whole effects of HMW-PVC exposure on X. laevis embryos.

L-Glutamic acid monosodium salt reduces the harmful effect of lithium on the development of Xenopus laevis embryos.

Many xenobiotics in the environment affect the human body in various ways. Among those xenobiotics, lithium chloride (Li, LiCl) and monosodium glutamate (L-glutamic acid monosodium salt, MSG) compounds affect the crucial processes of stem cell differentiation, cell proliferation, developmental gene expression, and overall development in animals. In this study, we aimed to examine the developmental effects of exposure to flavor enhancer MSG and LiCI medicament on Xenopus embryos using the frog embryo teratogenesis assay of Xenopus test. To this purpose, Xenopus laevis embryos were exposed to four different concentrations of MSG (120, 500, 750, 1000 mg/dL) and Li (0.02 g/L) alone and in combinations for a period of 96 h, and then normal, abnormal, and death ratios were determined in all exposure groups. Besides, length values of all groups and membrane potentials of fertilized and non-fertilized oocyte groups treated with 120- and 500-mg/dL MSG doses and 0.02-g/L LiCI dose were measured. Treatment with ADI (acceptable daily intake) dose of MSG alone did not lead to a substantial effect on the development of Xenopus laevis embryos. But, exposure to daily doses exceeding the ADI level (500, 750, 1000 mg/dL) caused significant harmful effects. Besides, Li-involving treatments caused dramatic deleterious effects on embryo development. MSG attenuated harmful effects of Li in MSG+Li combined treatments. Membrane potentials of non-fertilized oocytes and fertilized eggs were significantly changed in all groups that their membrane potentials were measured. Extrapolating these results into humans require similarly designed studies conducted on human embryos.

Residual NO modulates contractile responses and membrane potential in isolated rat mesenteric arteries.

Shear stress or vasocontriction causes endothelial nitric oxide (NO) release resulting in the regulation of vascular smooth muscle tone in small resistance arteries. Generation of NO is inhibited by nitric oxide synthase (NOS) inhibitors. In this study, we investigated the effect of residual NO, released even in the presence of NOS inhibitors, on the membrane depolarization and phenylephrine-induced contractions of smooth muscle. For this purpose, we used hydroxocobalamin (HC), an NO scavenger, in the presence of NOS inhibitiors, Nω-nitro- L-arginine (L-NA) or Nω-nitro-L-arginine methyl ester (L-NAME) in mesenteric arteries isolated from rats. Phenylephrine (0,01-10 µM), an α1-adrenoceptor agonist, led to depolarisation and concentration-dependent contraction in mesenteric arteries. The depolarisation and contractile responses were augmented by L-NA or L-NAME. Hydroxocobalamine (HC) or carboxy-PTIO (c-PTIO) also caused to further increase the membrane depolarization and contractions induced by phenylephrine in the presence of NOS inhibitors. Chemical removal of endothelium by saponin, tyrosin kinase inhibitor erbstatin A, but not calmodulin inhibitor calmidazolium inhibited the additional membrane depolarisation and contractile responses induced by L-NA or L-NAME and L-NA or L-NAME plus HC. These findings show that residual NO modulates the contractile responses in isolated rat mesenteric arteries by exerting a tonic inhibitor effect on the depolarization and vasoconstriction induced by phenylephrine.

Effects of GSM-like radiofrequency irradiation during the oogenesis and spermiogenesis of Xenopus laevis.

We aimed to evaluate the effect of GSM-like radiofrequency electromagnetic radiation (RF-EMR) on the oogenesis, and spermiogenesis of Xenopus laevis, and so the development of the embryos obtained from Normal Females+Normal Males (i.e. "N(F)+N(M)"); Normal Females+RF-exposed Males (i.e. "N(F)+RF(M)"); RF-exposed Female+Normal Male (i.e. "RF(F)+N(M)"); and RF-exposed Female+RF-exposed Male (i.e. "RF(F)+RF(M)". Various, assessments were performed to determine potential teratogenic effects and mortality, body growth and behavior on first generation embryos. After exposing adults frogs of both sexes to 900MHz RF-EMR (at 1.0W/kg) for 8h a day over a 5-week period, the embryos' specific energy absorption rate (SAR) was calculated. In our present study (control group; 2.2% abnormal, 0.0% dead); with the N(F)+RF(M) combination, the long-term exposure of adult males to GSM-like radiation at 900MHz (RF: 2W) for 5 week/8h/day resulted in normal, abnormal and dead embryo ratios of 88.3%, 3.3% and 8.3%, respectively (p<0.001). In the RF(F)+N(M) combination, long-term exposure (5 week/8h/day) of adult females led to normal, abnormal and dead embryo ratios of 76.7%, 11.7%, and 11.7%, respectively (p<0.001). And in the RF(F)+RF(M) combination, long-term exposure (5 week/8h/day) of both adult males and females led to normal, abnormal and dead embryo ratios of 73.3%, 11.7%, and 15%, respectively (p<0.001). With the exception RF(F)+RF(M) group (p<0.001), no significant changes were observed on body growth (lengths) in comparison to the control group. It was also observed that the offspring of female adult Xenopus exposed to RF-EMR during oogenesis exhibited a more aggressive behavior compared to the control group. Cell phones radiation can thus lead to detrimental effects in humans' male and female reproductive cells.

The effect of 900 and 1800 MHz GSM-like radiofrequency irradiation and nicotine sulfate administration on the embryonic development of Xenopus laevis.

The aim of this study was to investigate the effects of GSM-like radiofrequency electromagnetic radiation (RF EMR) and nicotine sulfate (NS) exposure on Xenopus embryonic development.The developmental effects of GSM-like RF-EMR (900-1800 MHz, at a SAR value of 1W/kg and NS on Xenopus laevis embryos were investigated). Following the application of radiofrequency radiation and/or NS administration, the embryos were closely examined in order to determine their possible teratogenic effects. Xenopus frogs obtained from the Department of Physiology of the Cukurova University, in accordance described by the Standard Guide of the American Society for Testing and Materials (ASTM). Following the exposure of Xenopus embryos to RF-EMR at 900 and 1800 MHz (1.0W/kg) for 4, 6 and 8h; the whole body specific energy absorption rate (SAR) of the embryos was calculated. With the exception of irradiation at 1800 MHz no dramatic developmental anomalies were observed in the Xenopus embryos in association with RF-EMR applications. Combined RF-EMR and NS applications resulted in dramatic abnormalities and death among the Xenopus embryos. The study results indicated that GSM-like RF-EMR (e.g. radiation from cell phones) was not as harmful to Xenopus embryos as might have been expected. However, the combined effects of GSM-like RF-EMR and NS on Xenopus embryos were more severe than the effect of RF-EMR or NS alone. In conclusion, the study results appear to suggest that the combined use of nicotine and cell phones might result in more pronounced detrimental effects on the health of smokers.

The impact of magnesium on isometric twitch parameters and resting membrane potential of the skeletal muscle in diabetic rats.

To present the relationship between oral magnesium supplementation, blood glucose, and changes in isometric twitch parameters, resting membrane potential (RMP), in the gastrocnemius muscle in diabetic rats. Sixty rats were used in this study. The rats were divided into four groups: control (drinking tap water, Group I, n = 15), control with treated with magnesium sulfate (10 g/L) (Group II, n = 15), diabetic (Group III, n = 15), and diabetic with treated with magnesium sulfate (10 g/L) (Group IV, n = 15). In Group II and IV, the level of plasma magnesium was increased comparing to those of the control group (p < 0.05). Isometric twitch tensions were decreased significantly in the Group III, but Group IV isometric twitch tensions were increased significantly. Group IV RMP values were close to the Group I. Hyperglycemia decreases gastrocnemius muscle isometric twitch tension and increases RMP in diabetic rats. Magnesium treatment can prevent these diabetic complications.

Effects of rosiglitazone with insulin combination therapy on oxidative stress and lipid profile in left ventricular muscles of diabetic rats.

PURPOSE: In this study, we tested the hypothesis that rosiglitazone (RSG) with insulin is able to quench oxidative stress initiated by high glucose through prevention of NAD(P)H oxidase activation. METHODS AND MATERIALS: Male albino Wistar rats were randomly divided into an untreated control group (C), a diabetic group (D) that was treated with a single intraperitoneal injection of streptozotocin (45 mg kg(-1)), and rosiglitazone group that was treated with RSG twice daily by gavage and insulin once daily by subcutaneous injection (group B). HbA1c and blood glucose levels in the circulation and malondialdehyde and 3-nitrotyrosine levels in left ventricular muscle were measured. RESULT: Treatment of D rats with group B resulted in a time-dependent decrease in blood glucose. We found that the lipid profile and HbA1c levels in group B reached the control group D rat values at the end of the treatment period. There was an increase in 3-nitrotyrosine levels in group D compared to group C. Malondialdehyde and 3-nitrotyrosine levels were found to be decreased in group B compared to group D (P < 0.05). CONCLUSION: Our data suggests that the treatment of diabetic rats with group B for 8 weeks may decrease the oxidative/nitrosative stress in left ventricular tissue of rats. Thus, in diabetes-related vascular diseases, group B treatment may be cardioprotective.

The embryonic development of Xenopus laevis under a low frequency electric field.

The aim of this study was to determine the effects of a low frequency electric field on the early embryonic development of frogs. The embryos of African clawed toads, Xenopus laevis, were exposed to a 20-µA electric current during the cleavage stages. The developmental processes of embryos during and after electric field exposure were monitored for teratogenic effects. All the embryos continuously exposed to the electric field died without undergoing any developmental processes. However, when the embryos were exposed to the electric field for 20-min periods (four times/over 2 d), the embryos developed into both normal tadpoles (70 %) and malformed tadpoles with light edema, reduced pigmentation, or axial anomalies, such as crooked tails. After exposure, the control embryos were at development stage 35.5 (2 d 2 h), while the normal embryos of the assay group were at developmental stage 41(3 d 4 h). There was a 1 d 2 h difference between the two developmental stages, revealing the importance of that time period for embryogenesis. In conclusion, the effects of electric current on Xenopus embryos are dependent on the initial developmental stage and the duration of exposure.

Oxidative stress and apoptosis in relation to exposure to magnetic field.

We investigated the effect of extremely low-frequency electromagnetic field (ELF-EMF) with pulse trains exposure on lipid peroxidation, and, hence, oxidative stress in the rat liver tissue. The parameters that we measured were the levels of plasma alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase as well as plasma albumin, bilirubin, and total protein levels in 30 adult male Wistar rats exposed to ELF. We also determined the percentage of apoptotic and necrotic cells of the kidney extracts from the animals by flow cytometry method. Apoptotic cell death was further characterized by monitoring DNA degradation using gel electrophoresis. The results showed an increase in the levels of oxidative stress indicators, and the flow cytometric data suggested a possible relationship between the exposure to magnetic field and the cell death. We showed significantly lower necrotic cell percentages in experimental animals compared to either unexposed or sham control groups. However, DNA ladder analyses did not differentiate between the groups. Our results were discussed in relation to the response of biological systems to EMF.

Deterioration of bone quality by streptozotocin (STZ)-induced type 2 diabetes mellitus in rats.

Patients with diabetes mellitus (DM) have various skeletal disorders and bone quality can be impaired in DM leading to fractures. Wistar albino male rats (270-300 g; n = 16) were assigned randomly to nondiabetic and diabetic rats (single dose intravenous injection of 45 mg/kg streptozotocin). All rats in each group were perpetuated for 8 weeks, and blood glucose levels as well as body weights were measured once weekly. Biomechanical measurements were performed at the mid-diaphysis of the left femur with tensile test. Extrinsic and intrinsic properties were measured or calculated. Bone mineral density (BMD) was also evaluated and measured by dual-energy X-ray absorptiometry. Cross-sectional area of the femoral shaft was evaluated by computerized tomography. Blood glucose levels in diabetic rats were significantly increased compared to that of the nondiabetic rats, while the body and femur weights were decreased (P < 0.05). In respect to the BMD, cross-sectional area and femur length, there were no statistically significant differences between the nondiabetic and diabetic rats (P > 0.05). The maximum load, ultimate stress, and toughness endpoints in diabetic rats were significantly decreased compared to that of the nondiabetics (P < 0.05). There were no statistically significant differences between the nondiabetic and diabetic rats with regard to the displacement and stiffness (P > 0.05). Femurs of diabetic rats had less absorbed energy than that in nondiabetics (P < 0.05). Ultimate strain was lower in diabetic rats than that in nondiabetics, while the elastic modulus was higher (P > 0.05). The bone quality of rats is decreased by streptozotocin-induced type 2 diabetes mellitus.

The effects of telmisartan on mechanical responses of left ventricular papillary muscle in rats with streptozotocin-induced diabetes mellitus.

The purpose of this study was to investigate the effects of telmisartan (5 × 10(-5) M) on the mechanical response of left ventricular papillary muscle in rats with streptozotocin-induced diabetes mellitus. We studied 32 rats; 16 were rendered diabetic by a single intravenous injection of streptozotocin (45 mg kg(-1) i.v.) and 16 formed a non-diabetic control group. Diabetic animals were divided into two groups: diabetic-telmisartan group and the diabetic-control group. Non-diabetic controls were further divided into the non-diabetic-telmisartan group and the non-diabetic-control group. We found: (1) Muscle twitch tension (P (0)) and contraction and relaxation rates were significantly lower in diabetic controls than in the other groups. (2) Telmisartan significantly increased P (0) in both diabetic and non-diabetic rats. (3) Times to peak tension and half-relaxation were significantly greater in groups DC and DT than in the non-diabetics. In conclusion, our data suggest that telmisartan attenuates diabetes-induced impairment of diabetic rat papillary muscles, and may thus be able to reduce cardiac complications in diabetes.

Repetitive 50 Hz pulsed electromagnetic field ameliorates the diabetes-induced impairments in the relaxation response of rat thoracic aorta rings.

PURPOSE: To evaluate the characteristic features of mechanical responses and the membrane potential changes induced by repetitive pulsed electromagnetic field (PEMF, 50 Hz, 5 mT) in thoracic aorta rings obtained from streptozotocin-induced diabetic and healthy control rats to determine if PEMF could ameliorate problems associated with diabetes. METHODS: Sixty male Wistar rats weighing 250-290 g were randomly divided into two experimental groups, each containing 30 animals. Streptozotocin was given via tail vein to produce diabetes mellitus (DM) in the first group rats. The second group rats were treated only with % 0.9 saline and considered as non-DM group. Both groups were also divided into two subgroups as DM + PEMF, DM + sham, PEMF and sham, each containing 15 animals. Although the DM + PEMF and PEMF groups were treated, the DM + sham and sham groups were not treated with PEMF. The PEMF treatment occurred four times daily for 30 min at 15-min intervals repeated daily for 30 days. Thoracic aorta rings from both DM and non-DM rats exposed to PEMF were evaluated for contraction and relaxation responses and membrane potential changes in the presence or absence of chemical agents that were selected to test various modes of action. RESULTS: Relaxation response of thoracic aorta rings was significantly reduced in DM than non-DM group. PEMF treatment significantly increased the relaxation response of the diabetic rings to acetylcholine, and reduced the concentration response to phenylephrine. Resting membrane potential was significantly higher in DM than in non-DM group. Inhibitors of nitric oxide (NO), both nitro-L-arginine (L-NO-ARG) and L-NO-ARG + indometacin combination, produced a significant transient hyperpolarisation in all groups. Inhibitors of potassium channel activity, charybdotoxin or apamine, produced a membrane depolarisation. However, PEMF did not induce any significant effect on the membrane potential in DM group. CONCLUSIONS: Diabetes reduced the relaxation response of thoracic aorta rings. It also affected the membrane potentials of the rings. Treatment with PEMF ameliorated the diabetes-induced impairments in the relaxation response of these rings.

The effects of rosiglitazone on oxidative stress and lipid profile in left ventricular muscles of diabetic rats.

We investigated the effect of rosiglitazone (RSG), a high-affinity ligand for the peroxisome proliferator-activated receptor gamma which mediates insulin-sensitizing actions, on the lipid profile and oxidative status in streptozotocin (STZ)-induced Type 2 diabetes mellitus (DM) rats. Wistar albino male rats were randomly divided into an untreated control group (C), a C + RSG group which was treated with RSG (4 mg kg(-1)) two times a day by gavage, a diabetic group (D) that was treated with a single intraperitoneal injection of STZ (45 mgkg(-1)), D + RSG group which were treated with RSG two times a day by gavage, respectively. Lipid profiles, HbA(1c) and blood glucose levels in the circulation and malondialdehyde (MDA) and 3-nitrotyrosine (3-NT) levels in left ventricular muscle were measured. Treatment of D rats with RSG resulted in a time-dependent decrease in blood glucose. We found that the lipid profile and HbA(1c) levels in D + RSG group reached the C rat values at the end of the treatment period. There was a statistically significant difference between the C + RSG and C groups in 3-NT levels. In group D, 3-NT and MDA levels were found to be increased when compared with C, C + RSG and D + RSG groups. In the D + RSG group, MDA levels were found to be decreased when compared with C and C + RSG. Our study suggests that the treatment of D rats with RSG for 8 weeks may decrease the oxidative/nitrosative stress in left ventricular tissue of rats. Thus in diabetes-related vascular diseases, RSG treatment may be cardioprotective.

Effects of rosiglitazone on altered electrical left ventricular papillary muscle activities of diabetic rat.

The action potential configuration of the left ventricular papillary muscle as well as the rosiglitazone-dependent changes in ventricular papillary muscle action potential amplitude were studied, and the duration was studied and compared in both healthy and diabetic rats. In this study, we used four groups: (1) nondiabetic control animals (C), (2) rosiglitazone-treated nondiabetic control animals (C+RSG), (3) diabetic animals (D), and (4) rosiglitazone-treated diabetic animals (D+RSG). Diabetes was induced by a single intravenous (i.v.) injection of streptozotocin (STZ). Conventional microelectrode techniques were applied to record action potentials after the establishment of diabetes (8 weeks after STZ treatment). Resting membrane potential (RMP) was decreased significantly in both RSG-treated C and D rats (from -70.2 +/- 0.7 to -63.2 +/- 0.7 and from -69.2 +/- 0.4 to -61.2 +/- 0.4). C+RSG and D+RSG groups showed increase in action potential amplitude compared with C and D groups (from 67.1 +/- 0.8 to 68.2 +/- 0.5 and from 67.1 +/- 0.8 to 80.1 +/- 0.8 and from 68.2 +/- 0.5 to 79.3 +/- 0.3) Depolarization time was significantly prolonged in diabetic rats (12.1 +/- 0.4 to 27.5 +/- 0.9). However, this prolongation in D+RSG group was significantly lower according to D group (from 27.5 +/- 0.9 to 19.2 +/- 0.7). There was no difference between C and C+RSG rats (12.1 +/- 0.4 to 11.6 +/- 0.2). Half repolarization time was also prolonged in diabetic rats (17.5 +/- 0.6 to 59.9 +/- 1.0). Moreover, D+RSG rats showed a slight and statistically insignificant difference according D rats (59.9 +/- 1.0 to 55.9 +/- 1.7). C+RSG rats showed a slight significant increase in half repolarization time compared with C group (17.5 +/- 0.6 to 29.4 +/- 0.7). Treatment of rats with RSG markedly decreased insulin resistance and also increased insulin sensitivity of the heart. Our data suggest that the beneficial effects of RSG treatment on the electrical activities of the diabetic rat papillary appear to be due to the diminished K+ currents, partially related to the decrease of hyperglycemia.

Urocortin induces endothelium-dependent vasodilatation and hyperpolarization of rat mesenteric arteries by activating Ca2+-activated K+ channels.

Urocortin, a member of corticotropin releasing factor (CRF) peptide family, has positive chronotropic and inotropic effects on heart and also shows a vasodilatory effect. However, the mechanism underlying its vasodilatory effect has yet to be elucidated. Endothelium-dependent relaxation of resistance arteries is mainly achieved by activation of K+ channels. Therefore, we investigated possible role of K+ channels and hyperpolarization for the vasodilatory effect of urocortin using the isolated perfused rat mesenteric arteries. Urocortin (0.2 nM) produced a slow-onset decrease in the perfusion pressure of the mesenteric vascular bed, which was elevated by an alpha1-adrenoceptor agonist, phenylephrine (2-4 microM). Urocortin also hyperpolarized the main mesenteric artery. Removal of endothelium with saponin treatment considerably inhibited the relaxation and hyperpolarization induced by urocortin. In contrast, the hyperpolarization was not significantly changed by cyclooxygenase inhibitor, indomethacin (1 microM) and/or nitric oxide synthase inhibitor, N(omega)-nitro-L-arginine (100 microM). Urocortin-induced relaxation was not affected by the combination of a guanylyl cyclase inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 1 microM), indomethacin and N(omega)-nitro-L-arginine. However, the relaxation and hyperpolarization were abolished by high extracellular potassium concentration (40 mM) or by a large conductance Ca(2+)-activated K+ channel blocker, charybdotoxin (1 nM). Glibenclamide (1 microM), an ATP-dependent K+ channel inhibitor, did not affect the relaxation and hyperpolarization. These results suggest that urocortin causes endothelium-dependent relaxation and hyperpolarization of rat mesenteric arteries, probably through the activation of charybdotoxin sensitive Ca2+-activated K+ channels. These findings also indicate an essential role of the endothelium for the urocortin-elicited vascular relaxation and hyperpolarization.

Pulmonary effects of deltamethrin inhalation: an experimental study in rats.

Deltamethrin is a synthetic pyrethroid widely used as the insecticide of choice especially for local vector mosquitoes in most countries. The application is mostly by cold aerosol spraying using vehicle-mounted equipment with a duration of 3-4 months during the summer. This experimental study aimed to evaluate the morphologic changes in the lungs caused by the inhalation of this insecticide. The study was performed on 30 mature male Wistar rats. While 10 of the rats were used as control group, 20 rats, separated into two groups, were exposed to 1:10 dilution of deltamethrin aerosol spray for 30 min each day for 45 days in doses of 6.0 and 12.0 mg/m3. The animals were sacrificed and tissue samples taken from the lungs were processed for both light microscopy and transmission electron microscopy. Light microscopic examination revealed heavy congestion, marked perivascular edema, and lymphoplasmocytic infiltration with focal nonspecific interstitial pneumonia, foamy macrophage accumulation, emphysema, peribronchial lymphoid tissue hyperplasia, and focal hemorrhage. Ultrastructurally, the ciliated cells of the airways appeared swollen with a few structurally abnormal cilia. Alveolar lining cells revealed mild degeneration and a slight hyperplasia in type II cells. Increases in the number of collagen bundles and edema in the alveolar septa were also noted.

The acute effect of trimetazidine on the high frequency fatigue in the isolated rat diaphragm muscle.

The objective of this study was to determine the acute effect of trimetazidine (TMZ) on the pre-fatigue, fatigue and post-fatigue contractile characteristics and tension-frequency relationships of isolated rat diaphragm muscle. Muscle strips were taken from the ventral-costal aspects of the diaphragm muscle of rats killed by decapitation. The muscle strips were suspended in organ baths containing Krebs solution, with a gas mixture of 95% O2 and 5% CO2 at 37 degrees C and pH 7.35-7.45. After determining the thermoregulation and optimum muscle length the muscles were subjected to direct supramaximal stimulation with 0.05 Hz frequency square pulses for periods of 0.5 msec to obtain control values. After adding 5 x 10(-6) and 5 x 10(-5) M trimetazidine solution to the respective bath media, the contractile parameters of the muscles were recorded. The contractile parameters were also recorded for both the trimetazidine and trimetazidine-free media after application of the high frequency fatigue protocols. Later, the tension-frequency relationship was determined by applying stimulating pulses of 10, 20, 50 and 100 Hz to the muscle strips. Whilst the twitch tension obtained from the 5 x 10(-6) and 5 x 10(-5) M trimetazidine media showed numerical increases compared to that of the controls, these were not statistically significant (p>0.05). The contraction time exhibited a dose dependent increase (p<0.001), whilst the contraction and relaxation rates did not differ significantly. The isometric contraction forces obtained with the different stimulating frequencies showed a significant increase in the tetanic contraction only at 100 Hz (p<0.05). A comparison of the pre- and post-fatigue twitch tensions in the trimetazidine media showed the post- fatigue twitch tensions to be significantly higher than those of the pre-fatigue contraction forces (p<0.05). In the 5 x 10(-6) and 5 x 10(-5) M trimetazidine media the increases in the post-fatigue contraction force were 22 and 30%, respectively. These results demonstrated that in isolated rat diaphragm muscle, TMZ significantly limited the mechanical performance decrease during fatigue. It is our opinion that trimetazidine contributed to the observed fatigue tolerance by eliminating the factors of fatigue, due to preservation of intracellular calcium homeostasis, provision of the ATP energy levels needed by ATPase dependent pumps and especially by keeping the intracellular pH within certain limits.

Nonsynergistic effects of trimetazidine and selenium combination therapy on renal ischemic-reperfusion injury in rats.

Reactive oxygen species (ROS) have been postulated to play a major role in postischemic acute renal injury. Moreover, lipid peroxidation has been described as an important pathway of ROS-induced postischemic acute renal failure. To evaluate effects of selenium (Se) and trimetazidine (TMZ) on postischemic renal failure, renal tissue malondialdehyde (MDA) and superoxide dismutase (SOD) concentrations were measured in Wistar rats with ischemic renal failure. Treatment groups consisted of rats treated with TMZ (5 mg/kg orally) or Se (30 microg/kg orally) or TMZ+Se for 15 days. Ischemic groups consisted of rats with clamped left renal arteries for 1 hour. Before left renal arterial clamping, right nephrectomy was performed; after 24 hours, left nephrectomy was done. The animals were divided into 5 groups. Group 1 (n=7) was the nonischemic control group without treatment; Group 2 (n=6) was the ischemic control group treated with physiologic solution; Group 3 (n=5) received TMZ; Group 4 (n=5) received Se; and Group 5 (n=6) received TMZ+Se for 15 days. After TMZ and Se treatment, right renal tissue MDA significantly decreased in Groups 3-5 when compared with those in Group 1. There was no significant difference between nonischemic and ischemic renal tissue MDA in Groups 3, 4, and 5. Postischemic renal tissue SOD levels were higher than nonischemic levels in Group 3. In Groups 4 and 5, no significant differences were observed between nonischemic and ischemic renal tissue SOD levels. Moreover, total scores obtained from histopathologic evaluation of ischemic and nonischemic kidney samples in Groups 3, 4, and 5 were similar, but these scores in Group 2 were significantly different from those of Groups 3, 4, and 5. These results indicate that, under these study conditions, TMZ, Se, and TMZ+Se treatments prevent lipid peroxidation in ischemic and nonischemic renal tissue. Moreover, these treatments prevent histologic findings of postischemic-perfusion renal injury.

Effects of trimetazidine and selenium on high-frequency fatigue in isolated rat diaphragm muscle.

Trimetazidine (TMZ), which has been used in numerous experimental studies, is applied nowadays with the aim of reducing myocardial ischemia. The aim of this study was to determine the prefatigue and postfatigue contractile characteristics associated with the relationship between the force and frequency of contraction in muscle. The study was conducted using diaphragm muscle isolated from 40 male Wistar rats weighing 230 to 270 g. The rats were divided into 4 groups of 10 animals each: controls and TMZ-, selenium (Se)-, and TMZ+Se-treated groups. The rats in the control group were treated with 2 mL of physiologic serum (SF), those in the second group with Se 30 microg/kg in 2mL of SF, those in the third group with TMZ 5 mg/kg in 2 mL of SF, and those in the fourth group with a combination of TMZ 5 mg/kg + Se 30 microg/kg in 2 mL of SF. All rats were treated twice daily for 15 days by means of gastric lavage. The rats were then killed by cervical dislocation. The diaphragm muscle bands were removed and placed in an organ bath. After a 2-hour thermoregulatory period, muscles were fatigued with 5-ms pulses at a frequency of 40 Hz. Force-frequency relationships were studied after the application of 10, 50, and 100 Hz and the development of contraction curves. Contraction forces for the groups treated with TMZ, Se, and TMZ+Se (16.1 +/- 1.2, 13.2 +/- 1.3, and 14.9 +/- 1.0 g, respectively) were significantly lower than for the control group (17.0 +/- 1.4 g) during the prefatigue period (P<.001). Similarly, postfatigue contraction forces for the treated groups (15.7 +/- 1.3, 8.8 +/- 1.0, and 12.0 +/- 1.4 g, respectively) were significantly lower than for the control group (12.4 +/- 1.2 g, P<.001, P<.001, and P<.05, respectively). A significant decrease was noted in postfatigue contraction forces and contraction and relaxation rates in the Se- and TMZ+Se-treated groups compared with prefatigue values (P<.001), but the difference was not significant. Force-frequency relationships were evaluated at 10, 50, and 100 Hz. The tetanic contraction forces for the control, Se-, TMZ-, and TMZ+Se-treated groups at 100 Hz were 81.3 +/- 5.7, 91.6 +/- 6.8, 65.3 +/- 5.0, and 84.9 +/- 7.5 g, respectively. In the TMZ-treated group, a significant increase was observed in tetanic contraction forces at 100 Hz compared with controls (P<.001); no significant changes were seen in the force-frequency relationships at 10 and 50 Hz. The decrease in the contraction force in the postfatigue period was prevented to a larger extent in the TMZ-treated group than in the TMZ+Se- and Se-treated groups.