OBJECTIVE: Liver failure following ischemia-reperfusion (I/R) injury is a major concern in liver surgery.The purpose of this study was to evaluate combination pretreatment with melatonin (MEL) and dexamethasone (DEX) on liver I/R model.Male Wistar rats (n = 60) were assigned to 5 groups of 12 animals each: (1) Sham: laparotomy without I/R; (2) I/R: hepatic I/R; (3) I/R+MEL: hepatic I/R+melatonin injected intraperitoneally (20 mg/kg); (4) I/ R+DEX: hepatic I/R+ dexamethasone injected intravenously (10 mg/kg); (5) I/R+MEL+DEX: hepatic I/R+ melatonin injected intraperitoneally+dexamethasone injected intravenously.The liver was subjected to ischemia by clamping the portal triad for 30 minutes and then reperfused for 6 hours after ischemia by removing the clamps.RESULTS: The levels of glutathione peroxidase (GPx) and superoxide dismutase (SOD) decreased after hepatic I/R in all groups.Levels of GPx and SOD were higher in I/R+MEL+DEX group compared to I/R, I/R+MEL and I/ R+DEX groups and they were signifi cantly higher in I/R+MEL group compared to I/R and I/R+DEX groups (p < 0.05).Levels of ALT, AST, TNF-α, hepatic tissue malondialdehyde (MDA), liver injury index, and apoptotic index increased after hepatic I/R.Levels of ALT, AST, tissue MDA, tissue injury index and apoptotic index were lower in I/R+MEL+DEX group compared to those in I/R, I/R+MEL and I/R+DEX groups, and in I/R+MEL they were signifi cantly lower than in I/R+DEX group (p < 0.05).TNF-α level was lower in I/R+MEL+DEX group compared to other groups and it was signifi cantly lower in I/R+DEX group than in I/R+MEL and I/R groups (p < 0.05).CONCLUSION: Combination therapy with melatonin and dexamethasone had better results in decreasing the liver injury compared to when each of them was administered alone (Tab.3, Ref. 58).
The aim of this study was to assess whether microRNA-146a and its adapter proteins TNF receptor associated factor6 (TRAF6) and interleukin-1 receptor-associated kinase-1 (IRAK1) may be changed in the kidney of streptozotocin-induced diabetic rats, following regular moderate exercise.Forty adult male Wistar rats were allocated randomly into four groups (n=10), including sedentary control (SC), sedentary diabetic (SD), healthy sixty-day exercise (H60E), and diabetic sixty-day exercise (D60E) groups. Diabetes was induced by an intraperitoneal injection of 60 mg/kg streptozotocin. After 48 h, blood glucose levels >250 mg/dl was included to diabetic rats. After 2 days of diabetes induction, the exercise protocol began. Animals were exposed to 5 days of consecutive treadmill exercise for 60 min/day with the 22 m/min speed for 60 days. The kidneys of the rats were removed and microRNA was extracted from them using the miRCURYTM RNA isolation kit.In diabetic rats, statistical analysis revealed a significant decrease in miR-146a expression, non-significant decrease in IRAK1 mRNA expression, and non-significant increase in TRAF6 and NF-kB mRNA expression compared to the SC group. Exercise led to a non-significant increase in the expression of miR-146a and NF-kB mRNA in the kidneys of the diabetic group as compared to the SD group, significant increase in TRAF6 and IRAK1 mRNA expression compared to the H60E group, and significant increase in TRAF6 mRNA expression compared to the SD group.The present data indicate that exercise might be able to help in the prevention in the diabetic nephropathy development.
Ischaemia/reperfusion (I/R) injury is commonly seen in the field of intestine surgical interventions, shock, trauma, and many other clinical conditions. Simvastatin is known to have antioxidant and anti-inflammatory properties. This study investigated the effect of simvastatin administration in a warm intestinal I/R model on TNF-alpha, antioxidant enzymes and intestinal tissue morphology. Thirty-six male wistar rats underwent laparotomy under general anaesthesia. Simvastatin was administered from four days before ischaemia induction. The rats were divided in to three groups (n = 12): the sham group, the I/R group, and the I/R + simvastatin group. Intestinal ischaemia was induced by superior mesenteric artery ligation with microvascular clamps for 60 minutes, and after ischaemia, blood perfusion was released into the tissue and a reperfusion phase was started, which lasted for 3 hours. After 3 hours, the animals were sacrificed and serum and tissue obtained for biochemical and histological study. In the simvastatin treated group, intestinal tissue injury, TNF-alpha level, and tissue malondealdehyde levels were significantly lower than in the I/R group (p < 0.05). Glutathion peroxidase and superoxide dismutase levels were significantly higher in the simvastatin treated group than in the I/R group (p < 0.05). Simvastatin pretreatment reduced intestinal I/R injury and was associated with down- -regulation of serum TNF-alpha and tissue malondealdehyde level, and simvastatin administration maintained cellular antioxidant enzyme contents compared to the I/R group after 3 hours reperfusion time.
Ischemia-reperfusion injury (IRI) is a common and important clinical problem in many different organ
systems. Once the blood flow and oxygen supply are reestablished, reperfusion enhances the injury caused by the
ischemic period .This phenomenon, known as ischemia/reperfusion (IR) injury, impacts directly on liver viability,
especially during transplantation and liver surgery. The purpose of this study was to evaluate combination
pretreatment of melatonin (MEL) and dexamethasone (DEX) on liver I/R model of lung injury. Male Wistar rats
(n=60) were assigned to 5 groups of 12 animals each: 1: Sham; Laparatomy without I/R 2: I/R; underwent hepatic
I/R. 3: I/R+MEL; hepatic I/R+ injected intraperitoneally melatonin (20 mg/kg). 4: I/R+DEX; hepatic I/R+ injected
intravenously dexamethasone (10 mg/kg). 5: I/R+MEL+DEX; hepatic I/R+ injected intraperitoneally melatonin +
injected intravenously dexamethasone. Liver subjected to ischemia by clamping portal triad for 30 minutes and was
reperfused for 6 hours after ischemia by removing the clamps. Levels of glutathione peroxidase (GPx) and
superoxide dismutase (SOD) decreased after hepatic I/R in all groups; levels of GPx and SOD were higher in
I/R+MEL+DEX group comparing to I/R, I/R+MEL and I/R+DEX groups significantly(P<0.05), and they were
higher in I/R+MEL group comparing to I/R and I/R+DEX groups but it was not significant. Lung tissue
malondialdehyde (MDA) ,lung injury index, and apoptotic index increased after hepatic I/R. Tissue MDA, tissue
injury index and apoptotic index were lower in I/R+MEL+DEX group comparing to I/R, I/R+MEL and I/R+DEX
groups significantly(P<0.05), and in I/R+MEL was lower than I/R+DEX group but it was not significant. Coadministration
of melatonin and dexamethasone had better results in decreasing the lung injury after hepatic I/R ,
comparing to administering each of them alone.
[Mohammad Taghizadieh, Babak Hajipour, Naser Ahmadi Asl, Ali Khodadadi, Mohammad Hossein Somi. Coadministration
of Melatonin and Dexamethasone Attenuates Lung Tissue Injury after Liver
Ischemia/Reperfusion.
<b><i>Objective:</i></b> To study the effect of erythropoietin (EPO) treatment on renal and lung injury following renal ischemia/reperfusion (I/R). <b><i>Materials and Methods:</i></b> Thirty male Wistar rats were assigned to three groups of 10 rats each. The first group was sham-operated, the second was subjected to renal I/R (30 min of ischemia followed by 24 h of reperfusion). The third group was subjected to renal I/R and treated with EPO in two doses: the first dose 1 h prior to ischemia (1,000 U/kg) and the second dose 6 h after ischemia (1,000 U/kg). <b><i>Results:</i></b> The renal and lung tissue injury index, tissue serum blood urea nitrogen and creatinine (Cr) were higher in the renal I/R group compared to the renal I/R + EPO group; the difference was statistically significant (p < 0.05). Kidney and lung tissue glutathione peroxidase and superoxide dismutase levels were higher in the renal I/R + EPO group than the renal I/R group; the difference was also statistically significant (p < 0.05). <b><i>Conclusion:</i></b> The data showed that EPO pretreatment could be effective in reducing renal and lung injury following renal I/R and could improve the cellular antioxidant defense system. Hence EPO pretreatment may be effective for attenuating renal and lung injury after renal I/R-induced injury during surgical procedures, hypotension, renal transplantation and other conditions inducing renal I/R.
Brain-derived neurotrophic factor (BDNF) is a member of neurotrophins family that plays a pivotal role in memory and learning. Brain-derived neurotrophic factor mediates health benefits of physical activity both in humans and animals. The nerve damage and cognitive impairment in diabetic rats are thought to be the result of reduced BDNF levels. The purpose of this study was to examine the effect of short- and long-term moderate forced exercise on BDNF levels in the hippocampus of type 1 diabetic rats.
Nephrotoxicity is an important side-effect of treatment with Methotrexate (MTX). Pentoxifylline (PTX) is an anti-inflmmatory and anti-oxidant agent. We hypothesized that pentoxifylline may affords renal protection by downregulating TNF-alpha as well as by improving cellular anti-oxidant activity.Forty five male Wistar rats were assigned to 3 groups of 15 animals each: Group 1: control group (0.9% saline). Group 2: MTX; injected with 20 mg/kg MTX intraperitoneally (i.p.). Group 3: MTX + PTX injected i.p. MTX (20 mg/kg) + PTX (50 mg/kg) i.p. PTX was administered since 3 days before MTX administration and continued for 6 days. After 6 days rats were anesthetized and serum sampled and renal tissue removed for biochemical and histological evaluation.Data showed that glutathione peroxidase (GPx), superoxide dismutase (SOD) activities were lower in PTX + MTX group comparing to MTX group significantly (p < 0.05). Renal tissue injury index and percent of TUNEL positive cells, renal tissue malondialdehyde (MDA) levels, serum BUN (Blood Urea Nitrogen), creatinine (Cr) and TNF-alpha levels were higher in MTX group comparing to MTX+PTX group significantly (p < 0.05).In this study, the increased level of tissue MDA and serum TNF-alpha level together may be suggested that the underlying mechanism is related to direct toxicity of MTX rather than blockage in folate synthesis in kidneys. PTX administration also attenuated renal tissue injury and number of apoptic cells and suppressed the elevation of BUN and Cr levels. However, further studies are essential to elucidate the exact mechanisms of MTX-induced renal toxicity, and protection and the effect of PTX.
'%3e%3cg id='e'%3e%3cg id='c' fill='none' stroke='%23fff' stroke-width='2'%3e%3cpath id='b' d='M0 1h26M1 10V5h8v4h8V5h-5M4 9h2m20 0h-5V5h8m0-5v9h8V0m-4 0v9' transform='scale(1.4)'/%3e%3cpath id='a' d='M0 7h9m1 0h9' transform='scale(2.8)'/%3e%3cuse xlink:href='%23a' y='120'/%3e%3cuse xlink:href='%23b' y='145.2'/%3e%3c/g%3e%3cg id='d'%3e%3cuse xlink:href='%23c' x='56'/%3e%3cuse xlink:href='%23c' x='112'/%3e%3cuse xlink:href='%23c' x='168'/%3e%3c/g%3e%3c/g%3e%3cuse xlink:href='%23d' x='168'/%3e%3cuse xlink:href='%23e' x='392'/%3e%3c/g%3e%3cg fill='%23da0000' transform='matrix(45 0 0 45 315 180)'%3e%3cg id='f'%3e%3cpath d='M-.548.836A.912.912 0 0 0 .329-.722 1 1 0 0 1-.548.836'/%3e%3cpath d='M.618.661A.764.764 0 0 0 .422-.74 1 1 0 0 1 .618.661M0 1l-.05-1L0-.787a.31.31 0 0 0 .118.099V-.1l-.04.993zM-.02-.85 0-.831a.144.144 0 0 0 .252-.137A.136.136 0 0 1 0-.925'/%3e%3c/g%3e%3cuse xlink:href='%23f' transform='scale(-1 1)'/%3e%3c/g%3e%3c/svg%3e)
