Comparación de los efectos de la dexmedetomidina administrada en 2 momentos diferentes para lesión de isquemia-reperfusión renal en ratones

ResumenJustificación y objetivosinvestigar los efectos de la dexmedetomidina sobre la insuficiencia renal isquémica en ratones.Métodosen el presente estudio, 26 ratones machos adultos, albinos Wistar, con un peso de 230-300g fueron divididos aleatoriamente en 4 grupos: seudooperado (n=5), isquemia-reperfusión (grupo IR, n=7), IR/tratamiento de reperfusión con dexmedetomidina (grupo Dex-R, n=7) e IR/tratamiento preisquemia con dexmedetomidina (grupo Dex-I, n=7). En el primer grupo, se realizó una seudooperación y no se aplicaron pinzamientos renales. En el grupo IR, la isquemia renal fue inducida por oclusión de las arterias y venas renales bilaterales durante 60min seguida por reperfusión durante 24h. En los grupos Dex-R y Dex-I, se llevó a cabo el mismo procedimiento quirúrgico destinado al grupo IR, y la dexmedetomidina (100μg /kg intraperitoneal) fue administrada 5min después de la reperfusión y antes de la isquemia. Al final de la reperfusión, fueron recogidas muestras de sangre, los ratones fueron sacrificados y el riñón izquierdo procesado para histología.Resultadoslos niveles de nitrógeno ureico en la sangre (BUN) de los grupos Dex-R y Dex-I eran significativamente más bajos que los del grupo IR (p=0,015; p=0,043), aunque el flujo urinario era significativamente mayor en el grupo Dex-R (p=0,003). La puntuación histopatológica renal del grupo IR fue significativamente mayor que la de los otros grupos. No hubo diferencia significativa entre los grupos Dex-R y Dex-I.Conclusioneslos resultados demostraron que la administración de dexmedetomidina redujo histomorfológicamente la lesión de IR renal. La administración de dexmedetomidina durante el período de reperfusión fue considerada más eficaz debido al aumento de producción de orina y a la disminución de los niveles de nitrógeno ureico en la sangre

Renal Ischemia/Reperfusion Injury in Diabetic Rats: The Role of Local Ischemic Preconditioning

Background. The aim of this study was to evaluate the effects of local ischemic preconditioning using biochemical markers and histopathologically in the diabetic rat renal IR injury model. Methods. DM was induced using streptozotocin. Rats were divided into four groups: Group I, nondiabetic sham group (n=7), Group II, diabetic sham group (n=6), Group III, diabetic IR group (diabetic IR group, n=6), and Group IV, diabetic IR + local ischemic preconditioning group (diabetic IR + LIPC group, n=6). Ischemic renal injury was induced by clamping the bilateral renal artery for 45 min. 4 h following ischemia, clearance protocols were applied to assess biochemical markers and histopathologically in rat kidneys. Results. The histomorphologic total cell injury scores of the nondiabetic sham group were significantly lower than diabetic sham, diabetic IR, and diabetic IR + LIPC groups. Diabetic IR group scores were not significantly different than the diabetic sham group. But diabetic IR + LIPC group scores were significantly higher than the diabetic sham and diabetic IR groups. Conclusion. Local ischemic preconditioning does not reduce the risk of renal injury induced by ischemia/reperfusion in diabetic rat model

Possible involvement of ghrelin on pain threshold in obesity

Pain threshold (or perception) can increase or decrease according to some factors like gender, depression or individual differences. Also, previous studies showed that pain threshold can change in obesity but, these studies on the effects of obesity on pain threshold have given controversial results. In the obese people who were exposed to pain stimulasyon to determined pain threshold, an increased pain threshold was observed. Contrarily, in the studies using electrophysiological test had lower pain threshold, which indicates a reverse correlation between degree of overweight and the threshold of the nociceptive reflex. These studies indicate possible interrelationships between the endogenous opioids, nociception and obesity or eating behavior. Nevertheless, its mechanism is still unclear. The endocrine changes that play an important role in obesity can lead an increase or decrease in pain threshold. There are a few researches about these hormonal factors which are related to pain pathways, that they are nociceptive (like leptin) or antinociceptive effect (like ghrelin, orexin A and B). Ghrelin is one of the hormones which is related to obesity. There are studies which prove the relationship between this hormone and the systems that play a role in pain modulation in the brain. However, there is no previous knowledge about the effects of ghrelin on pain threshold in obesity. But, many strong evidence are present to hypothesise that ghrelin may have effects on pain threshold. Obesity and fasting are the two main situations in which ghrelin secretion is mostly modified. Circulating ghrelin levels negatively correlate with BMI, meaning increased ghrelin secretion during fasting, malnutrition, cachexia, and in anorexia nervosa and reduced ghrelin secretion in obesity. Therefore, we have the opinion that ghrelin play an important role in obesity-pain relationship and/or regulate other systems that are related to pain pathway. Based on the above analyses, we propose a hypothesis that the diminution of the susceptibility to pain in lean subjects/animals may be induced by the increase in endogenous ghrelin activity, or increased of the susceptibility to pain in obese subject/animals may be induced by the decrease in endogenous ghrelin activity. (C) 2009 Elsevier Ltd. All rights reserved

IMMUNOHISTOCHEMICAL EXPRESSION OF HEPATOCYTE GROWTH FACTOR/c-MET IN THE HEART AND AORTA OF DIABETIC RATS

Context. Diverse physiological or pathological events which are stimulated or contributed by HGF/c-Met pathway overlap by processes that play roles in etiopathogenesis of diabetes

Analysis of the antinociceptive effect of systemic administration of tramadol and dexmedetomidine combination on rat models of acute and neuropathic pain

WOS: 000250099200002PubMed ID: 17651791The aim of the present study was to investigate the possible antinociceptive effect of systemic administration of tramadol and dexmedetomidine either alone or in combination on acute and neuropathic pain models in rats. The antinociceptive effects of intraperitoneal (i.p.) tramadol (520 mg/kg) and dexmedetomidine (5-20 mu g/kg) and three different combinations of tramadol+dexmedetomidine (5 + 5, 5 + 10 and 10+ 5, mg/kg+ mu g/kg, respectively) were measured by tail-flick and hot-plate methods in acute pain. The effects on the sciatic nerve ligation-induced neuropathic pain was tested by i.p. administration of tramadol (5 mu g/kg), dexmedetomidine (5 mu g/kg) and tramadol + dexmedetomidine combination (5 + 5) using a thermal plantar test. Sedation/motor-incoordination was assessed on rotarod. Tramadol and dexmedetomidine produced dose-related antinociception in tail-flick and hot-plate tests. In both tests, combination of these drugs produced an antinociceptive effect that is greater than that produced by tramadol. or dexmedetomidine alone at several time points. In hot-plate test, tramadol + dexmedetomidine combination (5 + 10) exerted the strongest antinociceptive effect, while tramadol + dexmedetomidine combination (10 + 5) was significantly most effective in tail-flick test. In the neuropathic pain, the antinociceptive effect exerted by tramadol + dexmedetomidine combination (5 + 5) was also significantly greater than their applications alone. In rotarod test, tramadol (30 and 40 mg/kg), dexmedetomidine (30 and 40 mu g/kg), tramadol+dexmedetomidine combination (10+10, 20+20) produced sedation/motor-incoordination, whereas tramadol (5-20 mg/kg), dexmedetomidine (5-20 mu g/kg) and tramadol + dexmedetomidine combination (5 + 5, 5 + 10 and 10 + 5) did not produce any effect on sedation/motor-incoordination. The combination of tramadol and dexmedetomidine was more effective in increasing the pain threshold in acute and neuropathic pain when compared with the administration of either of these drugs alone. (C) 2007 Elsevier Inc. All rights reserved

HGF/C-MET PATHWAY HAS A ROLE IN TESTICULAR DAMAGE IN DIABETES INDUCED BY STREPTOZOTOCIN

Objective. The aim of the study was to investigate the role of Hepatocyte Growth Factor (HGF)/c-Met pathway in testicular damage provoked by streptozotocin (STZ)induced diabetes and the effects of insulin treatment on the HGF/c-Met pathway

A pilot study: Infrared laser stimulation of the rat vagus nerves

The vagus nerve originating from the brainstem in the central nervous system is a long cranial nerve that reaches the neck, thorax, abdomen, and colon. It plays a role in autonomic nervous, cardiovascular, gastrointestinal, and immune systems. Electrical stimulation of the vagus nerve has become a standard method for the treatment of neuropathic pain and epileptic conditions over the years. Infrared laser nerve stimulation (ILNS) is an evolving technique that uses infrared laser energy to stimulate cells with electrochemical capacity without the need for external agents or physical contact. This pilot study explores infrared laser stimulation of the rat vagus nerve, in-vivo. An infrared pigtailed single-mode diode laser operating at 1505 nm in continuous-wave (CW) mode was used in this study for noncontact CW-ILNS. Successful CW-ILNS of the rat vagus nerve was observed after the CN reached a threshold temperature of similar to 44 degrees C with response times as short as 10 s. With more improvement in instrumentation, better optimization of stimulation parameters, and a higher sample size, CW-ILNS may show some potential in vagus nerve stimulation for preclinica

Effects of dexmedetomidine in conjunction with remote ischemic preconditioning on renal ischemia-reperfusion injury in rats

Background and objectives: The aim of this study was to evaluate the effects of remote ischemic preconditioning by brief ischemia of unilateral hind limb when combined with dexmedetomidine on renal ischemia-reperfusion injury by histopathology and active caspase-3 immunoreactivity in rats

Comparison of Direct and Remote Ischaemic Preconditioning of Renal Ischaemia Reperfusion Injury in Rats

WOS: 000449525500009PubMed: 30505608Objective: One of the methods that can be used to prevent ischaemia reperfusion (IR) injury is ischaemic preconditioning. The aim of this study was to evaluate and compare the effects of remote and direct ischaemic preconditioning (RIPC and DIPC) histopathologically in the rat renal IR injury model. Methods: After obtaining an approval from the Dokuz Eylul University School of Medicine Ethics Committee, 28 Wistar Albino male rats were divided into four groups. In Group I (Sham, n=7), laparotomy and left renal pedicle dissection were performed, but nothing else was done. In Group II (IR, n=7), after 45 minutes of left renal pedicle occlusion, reperfusion lasting 4 hours was performed. In Group III (DIPC+IR, n=7), after four cycles of ischaemic preconditioning applied to the left kidney, renal IR was performed. In Group IV (RIPC+IR, n=7), after three cycles of ischaemic preconditioning applied to the left hind leg, renal IR was performed. All rats were sacrificed, and the left kidney was processed for conventional histopathology. Results: The histopathological injury score of the kidney was significantly lower in the sham group compared with the other groups (p<0.01). The injury scores of the DIPC+IR and RIPC+IR groups were significantly lower than in the IR group (p<0.05). In the RIPC+IR group, the injury score for erythrocyte extravasation was found to be significantly lower than in the DIPC+IR group (p<0.05). Conclusion: In the present study, it was demonstrated that both DIPC and RIPC decreased renal IR injury, but RIPC was found to be more effective than DIPC. This protective effect requiresfurther detailed experimental and clinical studies

Effects of repeated administered ghrelin on chronic constriction injury of the sciatic nerve in rats

WOS: 000280100600010PubMed ID: 20561937Chronic constriction injury (CCI) is a peripheral mononeuropathic pain model that is caused by an injury to the peripheral nervous system and refractory to available conventional treatment. Mechanisms involved in neuropathic pain are still unclear. Previous studies reveal that proinflammatory cytokines contribute to CC-induced peripheral nerve pathology. Ghrelin, a novel identified gastric peptide, has been shown to have antinociceptive activity and also anti-inflammatory properties by decreasing proinflammatory cytokines. Therefore, the aim of the present study was to investigate the effects of ghrelin on the CCI and its relationship with proinflammatory cytokines in rats. Wistar rats underwent sciatic nerve ligation to induce CCI fallowed by repeated ghrelin administrations (50 and 100 mu g/kg i.p., once daily) for a period of 14 days. Mechanical hyperalgesia was assessed before surgery and at day 14 after CCI. TNF-alpha, IL-1 beta and IL-6 were measured in blood and spinal cord. The changes of sciatic nerve was assessed histologically by both light and electron microscopy. Ghrelin attenuated mechanical hyperalgesia, reduced spinal TNF-alpha and IL-1 beta levels and enhanced sciatic nerve injury with correlated morphometric recovery. These results indicate that the protective effect by ghrelin in the spinal cord is mediated through the suppression of TNF-alpha and IL-1 beta. Thus ghrelin may be a promising peptide in the management of neuropathic pain. (C) 2010 Elsevier Ireland Ltd. All rights reserved