Protective effects of Ficus carica seed oil on ischemia and reperfusion injury in a rat model of acute mesenteric ischemia.

BACKGROUND: The increase in free oxygen radicals and proinflammatory cytokines in the ischemia-reperfusion injury caused by acute mesenteric ischemia are the key responsibilities of intestinal histopathological alterations. It has been reported that Ficus carica and its various parts contain antioxidant and anti-inflammatory compounds recently. Thus, in the present study, we aimed to investigate how Ficus carica seed oil affects intestinal ischemia-reperfusion injury in a rat model. METHODS: In this study, 50 male Wistar albino rats were randomly divided into five equal groups. Negative control (NC), sham-operated (Sham), ischemia and reperfusion (IR), 3 ml/kg/day Ficus carica seed oil (FC3), 6 ml/kg/day Ficus carica seed oil (FC6). IR, FC3 and FC6 groups underwent ischemia and reperfusion procedure for 45+120 min. Only abdominal midline laparotomy was performed in the Sham group for 165 minutes. RESULTS: Tissue levels of TNFα and IL-1ß, which were proinflammatory cytokines, were significantly reduced in the FC6 group than the IR group (p<0.05). In FC3 and FC6 groups, the tissue MPO and MDA enzyme levels were significantly lower than the IR group, but there was a significantly greater decrease in the FC6 group than the FC3 group (p<0.05). SOD and CAT enzymes and reduced glutathione levels of FC3 and FC6 groups were significantly lower than IR group (p<0.05); however, there was no statistically significant difference between the FC3 and FC6 groups. FC3 and FC6 groups were histopathologically graded statistically lower than the IR group, and the FC6 group showed a significant decrease than the FC3 group (p<0.05). CONCLUSION: Oral administration of fig seed oil may reverse biochemical and histopathological findings resulting from ischemia-reperfusion injury in an experimental model of acute mesenteric ischemia in rats, probably because of its antioxidant and anti-inflammatory compounds.

Long-term protective effects of the combination of intermittent reperfusion and hypothermia on reperfusion injury in an experimental testicular torsion model.

INTRODUCTION: There are many significantfactors in testicular injury which determine the prognosis in testicular torsion. Reperfusion injury following detorsion also has a significant effect on testicular injury.This study was planned considering that with the implementation of intermittent reperfusion and hypothermia, reperfusion injury can be reduced, and such an application might have a positive effect on testicular tissue in the long term. MATERIALS AND METHODS: Forty adult male rats were divided into five groups as follows: Sham(Sh)(n = 8), Torsion(T)(n = 8), Intermittent reperfusion(IR)(n = 8), Hypothermia(H)(n = 8), and Intermittent reperfusion+hypothermia(IR+H)(n = 8). Except forGroup Sh, the left testicle was taken out of the scrotum in all groups, rotated three times counterclockwise, fixed back in the scrotum, and left for four hours.After four hours, and just before reperfusion, the testicle's detorsion was performed while holding the vascular structures in the proximal part of the torsed segment with an atraumatic vessel clamp, and thus, not allowing reperfusion in Groups T, IR, H, and IR+H. In Group T, the clamp was released immediately. In Group H, an ice-bag cooling was performed around the testis, and the clamp was released when the tissue temperature was reached and kept constant at 4 °C. In Group IR, the clamp was released, allowing reperfusion of five seconds, followed by reclamping, providing an ischemic status for ten seconds; this procedure was repeated ten times. In Group H+IR,an ice-bag cooling was performed around the testis, and the clamp was released when the tissue temperature was reached and kept constant at 4 °C. Then, reperfusion was applied for 5 s, followed by 10 s ischemia with reclamping. This procedure was repeated ten times.Tissue blood flow was provided for60 days of reperfusion in all groups. After 60 days, both testicles were excised under anesthesia in all living rats, and samples ofthe left testicle werereserved for biochemical and pathological examinations. At the end of the procedure, all animals were sacrificed by a high dose of anesthesia. RESULTS: It was biochemically and histopathologically determined that the tissues were preserved in the experimental groups compared to Group T, which was statistically significant (p < 0.05).However, no experimental group's superiority over each other was determined both biochemically and histopathologically (p > 0.05). CONCLUSION: Our long-term experimental study revealed that all methods were protective in testicular torsion. The authors believe that these methods can be applied in clinical practice because of their ease of application and no additional cost. On the other hand, the results of our study should further be supported by other experimental studies.

Comparison of the effects of intermittent reperfusion and hypothermia in preventing testicular ischemia-reperfusion injury in the testicular torsion model in rats.

INTRODUCTION: Reperfusion injury after detorsion in testicular torsion is a clinical problem. This study was planned to investigate the protective effect of intermittent reperfusion in hypothermia-applied testicles. MATERIALS AND METHODS: A total of 40 adult male rats were used, and 5 groups were created: sham (Sh; n = 8), torsion (T; torsion-detorsion) (n = 8), intermittent reperfusion (IR; n = 8), hypothermia (H; n = 8), and intermittent reperfusion+hypothermia (H+IR; n = 8). The left testicle was removed in all groups except in the Sh group, and it was rotated 3 times counterclockwise, fixed in the scrotum, and left for 4 h. After 4 h, the testicle was detorsioned in the groups T, IR, H, and H+IR. During detorsion, an atraumatic vessel clamp was applied in the proximal part of the vascular structures to prevent any reperfusion of the testicle. The clamp was opened immediately in the group T. In the group IR, the clamp was opened, a reperfusion of 5 s was applied; then, the clamp was closed again, and ischemia was created for 10 s; this procedure was repeated 10 times. In the group H, an ice bag cooling was performed around the testis. The tissue temperature was kept constant at 4 °C using a digital thermometer control. The testicle was cooled using an ice bag in the group H+IR; the same procedure was applied to the IR group. In all groups, reperfusion was performed for 1 h at the end of these procedures. The left testicle was removed from all rats; a portion of each testicle was separated for biochemistry testing, and some was separated for histopathological evaluation. At the end of the procedure, intracardiac blood was taken to examine oxidative stress parameters. At the end of the procedure, all animals were sacrificed after administration of a high dose of anesthesia. RESULTS: The authors observed that the tissue was preserved in the experimental groups and this was statistically significant (p<0.05). It was detected that the tissues were also histopathologically and significantly preserved in the groups IR, H, and H+IR. However, both biochemically and histopathologically, there was no superiority of hypothermia, intermittent reperfusion, or combined application (p>0.05). DISCUSSION: Both hypothermia and intermittent reperfusion alone protect tissue from IR damage. But no studies have been found in which these applications were used together. And as a result of this work, the combination of both methods did not show superiority over the effect they showed when they were used separately. The authors think that these methods can be applied clinically because of their ease of application and no additional costs; however, it should be supported by other studies.

Effect of experimentally induced hypothyroidism during gestation period on activity dependent neurotrophic factor (ADNF) in newborn rat brain tissue.

Purpose The aim of the study was to evaluate the effects of prenatal hypothyroidism on neonatal rats by the way of activity-dependent neuroprotective factor (ADNF) expression. Methods Twenty-one Wistar albino neonatal rats were divided into two subgroups; a control group and neonatal rats with experimental maternal hypothyroidism. Hypothyroidism was induced by using propylthiouracil (PTU). Neonatal rats obtained PTU from breast milk continuously for 1 week after birth. The rats from the control group were fed only normal feed and water. After birth, body weight and blood thyroid hormone levels were tested. Glial fibrillary acidic protein (GFAP), Slug, Numb, Notch-1 and ADNF antibodies were used for immunohistochemical analysis. Real-time polymerase chain reaction (RT-PCR) and Western blotting analyses were used to evaluate ADNF gene expression levels from 1-week-old rat's brain. Results There was no difference between the two groups for birth weights. The thyroxine (T4) level from the experimental group was <0.4 ng/mL, and it was 0.8 ng/mL for the control group. It was shown that, the results from the experimental group samples had significantly lower ADNF mRNA levels than control group (p < 0.05). The increase from GFAP and Numb expression and decrease from Slug expression were shown in the experimental group. Local differences were identified for ADNF and a decrease was shown in both sides of brain. There was no difference for Notch-1 expression for both groups. Conclusion In this study, decreasing ADNF expression might contribute to developing neurological problems in congenital hypothyroidism.

Protective effects of citicoline on TNBS-induced experimental colitis in rats.

The aim of this study was to investigate the effects of citicoline on the development of colitis and antioxidant parameters in rats subjected to tribenzene sulfonic acid (TNBS)-induced colitis. Twenty four Wistar Albino female rats were divided into four subgroups (n=6) (control, colitis control, colitis + 50 mg/kg citicoline, colitis + 250 mg/kg citicoline). Colitis was induced using an enema of TNBS and ethanol; following which citicoline was administrated for 3 days and effects of citicoline was subsequently evaluated. Based on microscopic damage scores, there was no difference between rats of the TNBS-colitis and 50 mg/kg citicoline treated groups, whereas treatment with 250 mg/kg citicoline, caused significant reduction in colon injury compared to that observed in rats of TNBS-colitis group. In terms of the biochemical analyses, myeloperoxidase (MPO), malondialdehyde (MDA), reduced glutathione (GSH), and IL-6 levels in rats from 250 mg/kg citicoline group were significantly different from that TNBS-colitis group. The levels of MPO, MDA, GSH and IL-6 in control rats were also significantly different those of rats in the TNBS-colitis group. Citicoline may have a positive protective effect on the inflammatory bowel disease treatment process and could, therefore, be used as an adjunct therapy in colitis. These effects of citicoline may exist through anti-inflammatory and antioxidant mechanism.

The antinociceptive effects of systemic administration of tramadol, gabapentin and their combination on mice model of acute pain.

OBJECTIVES: The aim of the present study was to investigate the possible antinociceptive effects of systemic administration of tramadol and gabapentin either alone or in combination on acute pain models in mice. METHODS: After obtaining the approval of Animal Ethics Committee; 96 BALB/c albino male mice were divided into 12 groups: (I) control without injection, (II) control treated with saline, (III)-(IV) mice treated with tramadol 10 mg/kg or 30 mg/kg, (V)-(VIII) mice treated with gabapentin; 30, 100, 200, 300 mg/kg respectively. In order to determine possible interactions between tramadol gabapentin and; mice received four different combinations of tramadol + gabapentin (30+30, 30+100, 30+200 and 30+300 mg/kg) (Groups IX-XII respectively). Mice received 0.1 ml solution for every 10 g of their weight. The drug was injected into peritonea. Thirty minutes after the drug injection, tail-flick and hot-plate tests were conducted. RESULTS: Ten and 30 mg/kg tramadol produced dose dependent antinociceptive effect in tail-flick and hot plate tests. Gabapentin had no antinociceptive effect in the tail flick test except 300 mg/kg dose, and had dose dependent antinociceptive effect in hot-plate test. In both tests, various combinations of tramadol and gabapentin produced an antinociceptive effect that is greater than that produced by tramadol and gabapentin alone. But, just 30 mg/kg tramadol + 300 mg/kg gabapentin combination caused statistically significant increase in both tests (p<0.05). CONCLUSION: When gabapentin and tramadol were used in combination, gabapentin had no additive antinociceptive effect except for 300 mg/kg in tail-flick and hot-plate tests. Tail-flick test showed that tramadol produced better antinociceptive effect than gabapentin.

Targeting SYK kinase-dependent anti-apoptotic resistance pathway in B-lineage acute lymphoblastic leukaemia (ALL) cells with a potent SYK inhibitory pentapeptide mimic.

The present study found that the pentapeptide mimic C-61, targeting the substrate binding P-site of SYK tyrosine kinase acted as a potent inducer of apoptosis in chemotherapy-resistant SYK-expressing primary leukemic B-cell precursors taken directly from relapsed B-precursor leukaemia (BPL) patients (but not SYK-deficient infant pro-B leukaemia cells), exhibited favourable pharmacokinetics in mice and non-human primates, and eradicated in vivo clonogenic leukaemia cells in severe combined immunodeficient mouse xenograft models of chemotherapy-resistant human BPL at dose levels non-toxic to mice and non-human primates. These in vitro and in vivo findings provide proof of principle for effective treatment of chemotherapy-resistant BPL by targeting SYK-dependent anti-apoptotic blast cell survival machinery with a SYK P-Site inhibitor. Further development of C-61 may provide the foundation for therapeutic innovation against chemotherapy-resistant BPL.

Protective effects of caffeic acid phenethyl ester on intestinal ischemia-reperfusion injury.

AIM: Intestinal ischemia reperfusion (IR) causes tissue injury in two ways, starting a pro-inflammatory cascade and oxidative stress. The aim of this study was to investigate the possible protective effects of caffeic acid phenethyl ester (CAPE), which has antioxidant and anti-inflammatory properties, against intestinal IR injury in rats. MATERIALS AND METHODS: Forty male Wistar-Albino rats were divided into five groups: Sham, IR, IR plus ethanol (vehicle), IR plus 10 mg/kg (IR + 10CAPE), and 30 mg/kg CAPE (IR + 30CAPE) at the 30-min ischemic period. Intestines were exteriorized and the superior mesenteric artery was occluded for 45-min ischemia and then the clamp was removed for 120-min reperfusion. After the experiment, the intestines were removed for biochemical and light microscopic examinations. Additionally, blood samples were taken for plasma TNF-alpha measurement. RESULTS: The TBARS levels of the IR and IR + Ethanol groups were higher than the Sham group (P < 0.05). Both CAPE treatments decreased TBARS levels in comparison with the IR group (P < 0.05). In both CAPE-treated groups, while the superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were increased compared to all other groups, which was similarly the case for the CAT activity compared to the Sham and IR + Ethanol groups (P < 0.05). There were no significant differences between GSH levels of all study groups. The TNF-alpha levels of the IR and IR + Ethanol groups were non-significantly increased compared to the Sham group (P > 0.05). The TNF-alpha levels of 10 and 30 mg/kg CAPE groups were non-significantly decreased compared to the IR group (P > 0.05). The tissue MPO activities of the IR and IR + Ethanol groups were higher than the Sham group (P < 0.05). The MPO activities of the IR + 10CAPE and IR + 30CAPE groups were not significantly different from the Sham group (P > 0.05). There was necrosis of mucosa in the IR and IR + Ethanol groups in light microscopic evaluations. Those changes were significantly reversed by 30 mg/kg CAPE treatment. CONCLUSION: The intestinal IR injury may be reversed by anti-inflammatory and antioxidant actions of the CAPE. However, 30 mg/kg CAPE treatment may be more efficient in preventing intestinal IR injury in rats.

The effects of caffeic acid phenethyl ester (CAPE) on TNBS-induced colitis in ovariectomized rats.

AIM: The aim of this investigation was to examine the effects of caffeic acid phenethyl ester (CAPE) on the development of colitis and antioxidant parameters in bilateral ovariectomized rats subjected to trinitrobenzene sulfonic acid (TNBS)-induced colitis. MATERIALS AND METHODS: Twenty-one Wistar Albino ovariectomized female rats were divided into four subgroups (n = 5 or 6) (colitis control, vehicle control, CAPE 10 and 30 mg/kg, respectively). Colitis was induced using an enema of TNBS and ethanol, following which CAPE was administrated for 3 days to induce colitis and effect of CAPE was subsequently evaluated. RESULTS: Based on microscopic damage scores, there was no difference between rats of the TNBS-colitis and the vehicle-treated groups, whereas treatment with CAPE 10 and 30 mg/kg, respectively, caused a significant reduction in colon injury compared to that observed in rats of the TNBS-colitis and vehicle-treated groups. The histologies of both treatment groups were not significantly different. In terms of the biochemical analyses, myeloperoxidase levels in rats from the CAPE 10 and 30 mg/kg groups were significantly different from that of the colitis control rats; however, the levels of malondialdehyde (MDA), catalase and reduced glutathione (GSH) were only significantly different from the levels found colitis control rats in rats administered 10 mg/kg. The levels of MDA, GSH and SOD in rats given CAPE were also significantly different from those of rats in the vehicle control group. These results were consistent with histological findings. CONCLUSION: CAPE may have a positive effect on the inflammatory bowel disease treatment process and could, therefore, be used as an adjunct therapy in colitis. These effects of CAPE may occur through antiinflammatory and antioxidant mechanisms.

Effects of tamoxifen on myocardial ischemia-reperfusion injury model in ovariectomized rats.

The purpose of this study is to examine the antiarrhythmic and antioxidant effects of tamoxifen, one of the selective estrogen modulators, in ovariectomized rats subjected to myocardial ischemia-reperfusion (I/R) injury. A month after ovariectomy, rats were divided into four groups: (I) ovariectomized controls without any treatment, (II) ovariectomized rats treated with vehicle dimethylsulfoxide (DMSO), (III)-(IV) ovariectomized rats treated with tamoxifen 1 or 10 mg/kg,sc daily for 14 days. To produce arrhythmia, the left main coronary artery was occluded for 7 min, followed by 7 min of reperfusion. The blood pressure (BP), heart rate (HR), electrocardiography (ECG) was recorded before and during the ischemia-reperfusion period. The blood levels of malondialdehyde (MDA), creatine kinase (CK), glutathione (GSH), glutathione peroxidase (GSH-Px), glutathione reductase (GR), and catalase (CAT) were measured after the rats were killed. Tamoxifen reduced the incidence of ventricular tachycardia (VT) on ischemia and reperfusion as well as the incidence and duration of reversible ventricular fibrillation (VF) on reperfusion. I/R injury caused a significant fall in GSH, GSH-Px as well as an increase in MDA and CK levels in the control group when compared to tamoxifen treated groups. The changes in levels of CAT and GR were however, not significant. In conclusion, our findings suggest that tamoxifen has cardioprotective effects against I/R injury in rats, likely its antioxidant properties.

Effects of melatonin supplementary on the sciatic nerve conduction velocity in the ovariectomized-aged rat.

OBJECTIVES: Melatonin is a potent antioxidant agent and an anti-aging hormone. Serum melatonin level declines during the menopause. Estradiol, a neuroprotective ovarian hormone, also decreases during the menopause. The purpose of this study is to evaluate the effect of melatonin supplementary on peripheral nerve function in the ovariectomized (OVX)-aged rats. METHODS: Randomly selected OVX-aged Wistar rats received injections of melatonin (5 or 20 mg/kg) daily either two or six weeks. Nerve conduction velocities and distal latencies were determined from the propagation of action potential recorded by using an extracellular electrophysiological technique. RESULTS: The mean distal latencies of melatonin-treated groups were shorter than that of the control group. Thus, the nerve conduction velocity was significantly greater in both two weeks and six weeks melatonin treated groups as compared to the controls (p<0.001). CONCLUSION: Melatonin alleviates the electrophysiological properties of the sciatic nerve in OVX-aged rats. Thus, melatonin supplementary may have a potential clinical application for the treatment of postmenopausal peripheral nerve degeneration.