Interleukin-18 Binding Protein Pretreatment Attenuates Kidney Injury Induced by Hepatic Ischemia Reperfusion.

OBJECTIVE: Acute kidney injury (AKI) is a serious condition that can be induced by liver transplantation, major hepatic resection or prolonged portal vein occlusion. AKI can increase the frequency of postoperative complications. In the current study, we aimed to investigate whether interleukin-18 binding protein (IL-18BP) pretreatment has a protective effect against possible kidney injury following liver ischemia-reperfusion (IR) achieved by Pringle maneuver in an experimental rat model. MATERIALS AND METHODS: A total of 24 male Wistar albino rats were included in this study. Animals were equally and randomly separated into 3 groups as follows: I, Sham group, II, IR group (1-hour ischemia and 4-hour reperfusion) and III, IR + IL-18BP group (50µg/kg IL-18BP was intraperitoneally administered 30 minutes before surgery). Blood, liver and kidney samples were collected for histopathological and biochemical (hepatic and renal function, nitric oxide, malondialdehyde and glutathione levels) analysis. In addition, proinflammatory cytokines including tumor necrosis factor α, IL-1ß and IL-6 levels were measured in kidney tissues. RESULTS: IL-18BP has improved kidney functions in acute kidney damage, restored structural changes, exhibited anti-inflammatory effects by decreasing proinflammatory cytokines and regulated the oxidative stress parameters by antioxidant effect. CONCLUSIONS: Current study would be the first to evaluate the protective, antioxidant and anti-inflammatory effects of IL-18BP on renal damage induced by liver ischemia (1 hour) and reperfusion (4 hours). As a result, we have demonstrated that AKI may develop after hepatic IR with Pringle maneuver and IL-18BP pretreatment can attenuate this damage. By this way, complications related to liver IR could be minimized and also postoperative hospitalization durations, treatment costs and healing periods could be decreased.

Investigation of the effect of safranal and crocin pre-treatment on hepatic injury induced by infrarenal aortic occlusion.

Ischemia-reperfusion (IR) injury of the liver is an unresolved problem that occurs during certain surgical approaches, including hepatic, cardiac and aortic operations. In this study we aimed to investigate whether crocin and safranal had protective effects on liver IR injury induced in an infrarenal aortic clamping (IRAC) model. Male Wistar-Albino rats (n=32) were divided into four groups with 8 animals each as follows: Sham, IR, IR+crocin, and IR+safranal. The infrarenal aorta (IRA) was clamped for 60min for the ischemic period and allowed to reperfuse for 120min. Blood and tissue samples were collected for biochemical, histological and immunohistological analysis. Plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were found to be significantly higher in the IR group than the sham group (respectively; p=0.015, p<0.001). There were significant differences between the IR group and the IR+crocin group or the IR+safranal group in AST levels (respectively; p=0.02, p<0.001). ALT showed a significant decrease in the IR+crocin group compared to the IR group (p<0.05). We also observed histopathological changes among the groups. Bax and Caspase-3 expression in the IR group was remarkably higher than in the other groups. Caspase-3 and Bax expression in the IR+crocin and the IR+safranal groups were significantly lower than in the IR group. Nevertheless, there were no significant differences in BCL2 expression among the groups. IRAC is a cause of IR injury in the liver. This study showed that crocin and safranal have protective effects on IR induced liver injury.

Investigation of the effect of crocin pretreatment on renal injury induced by infrarenal aortic occlusion.

OBJECTIVE: Ischemia and reperfusion (IR) injury is an important complication of abdominal aortic surgery, and it mainly affects the lower extremities and remote organs. In the present study, we aimed to investigate the possible protective effect of crocin in IR-mediated kidney damage. MATERIALS AND METHODS: A total of 24 adult male Wistar-Albino rats were equally and randomly separated into three groups as follows: sham laparotomy, IR, and IR + crocin. Infrarenal aortic occlusion and reperfusion was applied for 1 and 2 h, respectively. Tissue samples were removed and collected. Biochemical and histopathologic analyses were performed. RESULTS: Urea, blood urea nitrogen, creatinine, renal tissue tumor necrosis factor α, interleukin (IL)-6, IL-18, interferon gamma, IL-1ß, total oxidant status, and oxidative stress index levels were significantly higher in IR group, when compared with other groups. These improvements were also demonstrated with some parameters including total score of histopathologic damage, Tunel, Bax, and Caspase-3 expression levels, and these parameters were prominently higher in the IR group, when compared with the other groups. Nevertheless, Bcl2 expression degree was prominently lower in the IR group than those in the other two groups. CONCLUSIONS: Data established from the present study suggest that crocin can preclude renal damage in infrarenal aortic occlusion models.

The protective effect of melatonin on remote organ liver ischemia and reperfusion injury following aortic clamping.

BACKGROUND: Severe local and systemic tissue injuries can occur after restoration of tissue oxygenation which is also known as reperfusion injury. Our objective was to investigate the possible protective effects of melatonin against IR damage in hepatic tissue following infrarenal aortic occlusion. METHODS: A total of twenty-one male Wistar-albino rats separated into three groups as follows: Group I: Laparotomy and dissection of the infrarenal abdominal aorta (AA) were concurrently performed. Group II: About 1 ml of 0.9% saline was intraperitoenally administered 30 min before and after the occlusion operation. After laparotomy and dissection, infrarenal AA was clamped for 30 minutes and then was exposed to two hours of reperfusion. Group III: The melatonin was administered 30 min before clamping of the infrarenal AA then 30 min of ischemia and two hours of reperfusion was applied. RESULTS: Serum aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase levels were remarkably higher in IR group, when compared with the sham group, and the laboratory tests returned to normal levels in IR+MEL group after treatment. Although serum IL-1ß, IL-6, IL-18, TNF-α, and IFN- γ levels have decreased in treatment group following melatonin administration, this decrement was statistically significant for serum IL-18, TNF-α, and IFN- γ parameters compared with the IR group. Serum levels of TOC and OSI were decreased and tissue levels of TAC were increased by melatonin. CONCLUSION: As a result of this study, it can be suggested that melatonin has antioxidant, anti-inflammatory and hepatoprotective effects in case of IR. KEY WORDS: Aortic occlusion, Injury, Ischemia/Reperfusion, Liver, Melatonin.

Effects of thymoquinone against cisplatin-induced cardiac injury in rats.

PURPOSE: T o investigate the possible protective effect of thymoquinone (TQ) in cisplatin (CP) induced myocardial injury. METHODS: A total of 28 adult male Wistar-Albino rats were randomly and equally divided into four groups as follows: Group 1 (control), Group 2 (CP at 15 mg/kg dose), Group 3 (TQ 40 mg/kg/day for two days prior to CP injection and on third day, CP at 15 mg/kg dose was intraperitoneally administered and TQ treatment continued until fifth day) and Group 4 (TQ at 40mg/kg/day dose for five days). RESULTS: There was a significant increment in CP group in terms of congestion, edema and pycnotic nuclei in myocardial fibers, comparing with other groups. TQ group exhibited significant increase in expression of antiapoptotic protein Bcl-2, comparing with CP group (p<0.05). In only CP administered group, expression of antiapoptotic protein Bcl-2 was lowest comparing with other groups. CONCLUSION: Established data indicate that cisplatin is cardiotoxic and thymoquinone may be useful in treating CP-induced cardiac injury.

Antioxidant, Antiapoptotic and Inflammatory Effects of Interleukin-18 Binding Protein on Kidney Damage Induced by Hepatic Ischemia Reperfusion.

OBJECTIVE: Acute kidney injury (AKI) is a serious condition that can be induced by liver transplantation, major hepatic resection or prolonged portal vein occlusion. The AKI can increase the frequency of postoperative complications. In the current study, we aimed to investigate whether interleukin-18 binding protein (IL-18BP) pretreatment has a protective effect against possible kidney injury-mediated liver ischemia-reperfusion (IR) achieved by Pringle maneuver in an experimental rat model. MATERIALS AND METHODS: A total of 21 Wistar albino rats were included in this study. Animals were equally and randomly separated into 3 groups as follows: Sham (n = 7), IR group (n = 7) and IR + IL-18BP group (n = 7). Serum aspartate transaminase, alanine aminotransaminase and lactate dehydrogenase enzyme activities and serum urea and creatinine levels were determined. Tumor necrosis factor-α, IL-6, IL-1ß, interferon gamma, total oxidant status, total antioxidant status and oxidative stress index were measured in kidney tissue homogenate samples. Histopathological examination and immunohistochemical Caspase-3 staining were applied to examine the general morphologic structure and apoptosis. RESULTS: Renal total oxidant status; oxidative stress index; IL-18 levels; serum aspartate transaminase, alanine aminotransaminase and lactate dehydrogenase activities and creatinine levels were significantly lower in IR + IL-18BP group, when compared with the IR group. Beside this, total antioxidant status levels were remarkably higher in IR + IL-18BP group, when compared with the IR group. The caspase-3 expression degree in IR group was remarkably higher than other groups. CONCLUSIONS: It has been demonstrated that IL-18BP pretreatment may have inflammatory, antioxidant and antiapoptotic effects against AKI induced by hepatic IR.

The antioxidant and antiapoptotic effects of crocin pretreatment on global cerebral ischemia reperfusion injury induced by four vessels occlusion in rats.

AIMS: Cerebral ischemia reperfusion (IR) injury is a process in which oxidative and apoptotic mechanisms play a part. Neuroprotective agents to be found could work out well for the efficient and safe minimization of cerebral IR injury. Crocin is a strong antioxidant agent; however the influence of this agent on the experimental cerebral ischemia model has not been studied extensively and thus it is not well-known. The objective of our study was to investigate the antioxidant, antiapoptotic and protective effects of crocin on the global cerebral IR induced by four-vessel occlusion. MAIN METHODS: A total of 30 adult female Sprague-Dawley rats were equally and randomly separated into three groups as follows: sham, IR and IR+crocin (40mg/kg/day orally for 10days). 24h after electrocauterization of bilateral vertebral arteries, bilateral common carotid arteries were occluded for 30min and reperfused for 30min. Oxidative stress parameters (TAS, TOS, OSI), haematoxylin and eosin staining, caspase-3 and hypoxia-inducible factor-1 alpha (HIF-1α) expressions and TUNEL methods were investigated. KEY FINDINGS: There was a significant difference between the IR and sham groups by means of OSI level, histopathological scoring, caspase-3, HIF-1α and TUNEL-positive cell parameters. We have also observed that pre-treatment with crocin reduced these parameter levels back to the baseline. SIGNIFICANCE: The data obtained from the present study suggest that crocin may exert antiapoptotic, antioxidant and protective effects in IR-mediated brain injury induced by four-vessel occlusion. To the best of our knowledge, this would be the first study to be conducted in this field.

Prognostic value of perihematomal edema area at the initial ED presentation in patients with intracranial hematoma.

OBJECTIVE: Intracerebral hemorrhage (ICH) is a potentially life-threatening condition. Interventions and treatments should be managed on time to reduce mortality. It has been put forth that perihematomal edema absolute volume (PHEAV) is related to mortality, however the effect of perihematomal edema absolute area (PHEAA) on mortality is unknown. The objective of this study was to evaluate the effect of PHEAA on 30-day mortality in patients with ICH. METHODS: Patients were screened with ICD-9, retrospectively. 106 patients were included in the study. Clinical data were obtained from the patient files. Computed tomography (CT) was acquired from the hospital imaging database. PHEAV and PHEAA were measured via CT by two clinicians blinded to the study protocol. The predictors of 30- day mortality were examined. RESULTS: Forty-three (40.6%) patients died within 30days. Older age, lack of trauma, low Glasgow coma scale and high blood glucose were associated with high mortality (P≤.001). PHEAV and PHEAA values were higher in nonsurvivors (P<.001). PHEAA was detected as an independent predictor of 30-day mortality. The cutoff value of PHEAA for mortality was 33.41cm(2) (sensitivity: 84.4%, specificity: 59.0%). There was no difference between receiver operating characteristic curves of PHEAA and PHEAV (P=.55). CONCLUSION: In contrast to PHEAV, PHEAA is a simple value which can be measured without the requirement of any additional techniques or extra costs which can be quickly applied and which is an independent indicator of 30-day mortality. PHEAA can accelerate physician interventions for patients with ICH within several hours of ED admission.

The effects of IL-18BP on mRNA expression of inflammatory cytokines and apoptotic genes in renal injury induced by infrarenal aortic occlusion.

BACKGROUND: Renal injury is an important complication of infrarenal aortic occlusion (IAO), which is mainly encountered during the postoperative period. Aortic clamping procedure may lead to turbulent blood flow and eventually vasoconstriction at renal arterial level of the abdominal aorta. IL-18BP has well-known antioxidant and anti-inflammatory properties. In this study, we aimed to determine whether IL-18BP has anti-inflammatory, antiapoptotic, antioxidant, and protective effects on acute kidney damage induced by IAO rat model. MATERIALS AND METHODS: A total of 30 adult male Wistar-Albino rats were equally and randomly separated to three groups as follows: SHAM laparotomy, ischemia-reperfusion (IR), and IR + IL-18BP. We applied 30-min IAO and 2-h reperfusion. Inflammatory cytokine levels (TNF-α, IL-1ß, IL-18, IL-6, and IFN-γ) and oxidative stress parameters (TAS, TOS, and OSI) were measured. In addition to this, urea and creatinine levels, histopathology of kidney, mRNA expression levels of inflammatory cytokines, and apoptotic genes were investigated. RESULTS: Urea and creatinine, tissue and serum levels of TNF-α, IL-6, IL-18, IFN-γ, and TOS, and oxidative stress index (OSI) were found significantly lower in IR + IL-18BP group, when compared to the IR group. Moreover, mRNA expression levels of inflammatory cytokines and apoptotic genes were prominently depressed in IR + IL-18BP pre-treatment group in histopathologic examination, there was a significant difference between the IR and other three groups (P < 0.001). These improvements were demonstrated with a total score of histopathologic damage. In our previous studies, we have demonstrated that IL-18BP has antioxidant, inflammatory, and protective effects on liver and spinal cord IR injury. Data established from the present study suggest that IL-18BP may exert anti-inflammatory, antiapoptotic, antioxidant, and protective effects on IAO-induced acute kidney injury in rats, and this would be the first study to be conducted in this field. CONCLUSIONS: Data established from the present study suggest that IL-18BP may exert anti-inflammatory, antiapoptotic, antioxidant, and protective effects on IAO-induced acute kidney injury in rats.

The effect of enoxaparin on seroma and mesh-tissue adhesion in a hernia model.

The aim of this study was to investigate whether enoxaparin (ENX) administration would increase seroma risk and worsen mesh tissue recovery in an experimental rat hernia repair model. Fifty-six adult male Wistar-Albino rats were included in the study. Rats were equally and randomly separated into seven groups: Group 1, Control, only subcutaneous dissection was performed; group 2, Sham, Hernia defect was primary sutured; Group 3, Prolene mesh; Group 4, Dual mesh; Group 5, ENX + Sham; Group 6, ENX + Prolene mesh; Group 7, ENX + Dual mesh. ENX was subcutaneously injected at a dose of 180 U/kg per day for 7 days. Rats were killed after the amount of subcutaneous seroma was determined by ultrasound on day 7 following the surgical procedure. Mesh-tissue healing was evaluated using histopathological and immunohistochemical (CD31) staining methods. The mean seroma amount significantly increased in Groups 5-7 compared to Groups 2-4. CD31 immunostaining showed a reduction in neovascularization in Groups 6 and 7, compared to Groups 3 and 4. Neovascularization decreased and hemorrhage, necrosis and oedema findings remarkably increased in Groups 6 and 7, when compared to Groups 3 and 4. Fibroblastic activity and inflammation were more prominent in Groups 3 and 4. It should be kept in mind that ENX interferes with inflammation, which is desired in the early period of healing and leads to an increase in overall seroma amount with anti-coagulant effects, which in turn may disrupt wound healing and mesh-tissue adhesions, as was indicated in our study.

Effects of thymoquinone against cisplatin-induced cardiac injury in rats

PURPOSE: T o investigate the possible protective effect of thymoquinone (TQ) in cisplatin (CP) induced myocardial injury. METHODS: A total of 28 adult male Wistar-Albino rats were randomly and equally divided into four groups as follows: Group 1 (control), Group 2 (CP at 15 mg/kg dose), Group 3 (TQ 40 mg/kg/day for two days prior to CP injection and on third day, CP at 15 mg/kg dose was intraperitoneally administered and TQ treatment continued until fifth day) and Group 4 (TQ at 40mg/kg/day dose for five days). RESULTS: There was a significant increment in CP group in terms of congestion, edema and pycnotic nuclei in myocardial fibers, comparing with other groups. TQ group exhibited significant increase in expression of antiapoptotic protein Bcl-2, comparing with CP group (p<0.05). In only CP administered group, expression of antiapoptotic protein Bcl-2 was lowest comparing with other groups. CONCLUSION: Established data indicate that cisplatin is cardiotoxic and thymoquinone may be useful in treating CP-induced cardiac injury.

Effects of electromagnetic radiation exposure on bone mineral density, thyroid, and oxidative stress index in electrical workers.

BACKGROUND: In the literature, some articles report that the incidence of numerous diseases increases among the individuals who live around high-voltage electric transmission lines (HVETL) or are exposed vocationally. However, it was not investigated whether HVETL affect bone metabolism, oxidative stress, and the prevalence of thyroid nodule. METHODS: Dual-energy X-ray absorptiometry (DEXA) bone density measurements, serum free triiodothyronine (FT3), free thyroxine (FT4), RANK, RANKL, osteoprotegerin (OPG), alkaline phosphatase (ALP), phosphor, total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) levels were analyzed to investigate this effect. RESULTS: Bone mineral density levels of L1-L4 vertebrae and femur were observed significantly lower in the electrical workers. ALP, phosphor, RANK, RANKL, TOS, OSI, and anteroposterior diameter of the left thyroid lobe levels were significantly higher, and OPG, TAS, and FT4 levels were detected significantly lower in the study group when compared with the control group. CONCLUSION: Consequently, it was observed that the balance between construction and destruction in the bone metabolism of the electrical workers who were employed in HVETL replaced toward destruction and led to a decrease in OPG levels and an increase in RANK and RANKL levels. In line with the previous studies, long-term exposure to an electromagnetic field causes disorders in many organs and systems. Thus, it is considered that long-term exposure to an electromagnetic field affects bone and thyroid metabolism and also increases OSI by increasing the TOS and decreasing the antioxidant status.

Ligamentum flavum thickening at lumbar spine is associated with facet joint degeneration: An MRI study.

OBJECTIVE: Degenerative changes in posterior elements of the spine such as thickening or hypertrophy of the ligamentum flavum (LF) may result in spinal stenosis. In the present study, we aimed to investigate the potential factors including age, intervertebral disc degeneration (IDD), facet joint degeneration (FJD), end plate degeneration (EPD), which may affect LF thickening and to reveal the relationship among those factors at each level of lumbar spine by evaluating the magnetic resonance images (MRI). METHODS: A total of 200 individuals with low back and/or leg pain complaints who had undergone lumbar MRI were included in this study. The thickness of LF, FJD, IDD and EPD were assessed at all lumbar levels. RESULTS: Totally 1000 end plates, 1000 intervertebral discs and 2000 facet joints were evaluated and the thicknesses of 2000 LFs were measured from MRI images of 200 patients (100 males and 100 females). The mean age was 46.87 ± 12.47 years. LF thickness was strongly associated with FJD especially on the ipsilateral side. Age and IDD were correlated at whole vertebral levels. The age related changes (LF thickness, FJD, IDD and EPD) were more prominent at L4-L5 vertebral level. However, gender had no effect on LF thickness. CONCLUSION: The results of this study suggest that LF thickening may occur independently or could be associated with FJD especially on the ipsilateral side and this relationship is due to the vertebral level. The degree of disc degeneration increases with age and age related changes may be predominantly observed at L4-L5 vertebral level.

Interleukin 18--binding protein ameliorates liver ischemia--reperfusion injury.

BACKGROUND: The aim of this study was to investigate the possible protective effect of interleukin 18-binding protein (IL-18BP) on ischemia-reperfusion (I/R)-induced liver injury in experimental rat models. Liver is one of the most affected organs from I/R process. IL-18 is an important proinflammatory cytokine, which may induce some events such as production of reactive oxygen substances and release of various cytokines. IL-18BP acts as an inhibitor of IL-18. The relationship between IL-18 and IL-18BP has an important place in inflammatory process. MATERIALS AND METHODS: Rats were equally divided into three groups as follows: sham: Hepatic pedicle dissection was done, but hepatic pedicle clamping was not used. I/R: Sixty minutes of ischemia and 2 h of reperfusion were applied. IR + IL-18BP: Recombinant human IL-18BP (100 µg/kg) was administered 30 min before the surgery. Hepatic pedicle was clamped during 60 min of ischemia and 2 h of reperfusion was achieved. RESULTS: Liver enzyme levels were significantly lower in the IR + IL-18BP group, when compared with the I/R group. Serum and tissue levels of tumor necrosis factor-α, IL-6, and IL-18 were considerably lower in the IR + IL-18BP group, when compared with the I/R group, but hepatic interferon-γ and IL1ß levels were not significant. Serum oxidative stress index level was significantly higher in the I/R group, when compared with the IR + IL-18BP group. In immunostaining, it was observed that pathologic changes were lower in IR + IL-18BP group than the I/R group. CONCLUSIONS: IL-18BP exhibited anti-inflammatory, antioxidant, and protective effects in I/R-mediated hepatic injury via regulating some liver enzyme activities and cytokine levels. Additionally, these effects have been verified by histomorphologic examination and oxidative stress markers.

Cabazitaxel causes a dose-dependent central nervous system toxicity in rats.

BACKGROUND: Chemotherapeutic agents may lead to serious neurological side effects, which in turn can deteriorate the quality of life and cause dose limiting. Direct toxic effect or metabolic derangement of chemotherapeutic agents may cause these complications. Cabazitaxel is a next generation semi-synthetic taxane derivative, which is effective in both preclinical models of human tumors sensitive or resistant to chemotherapy and in patients with progressive prostate cancer despite docetaxel treatment. AIM: The primary aim of this study was to investigate the central nervous system toxicity of Cabazitaxel. Secondary aim was to investigate the safety dose of Cabazitaxel for the central nervous system. METHODS: A total of 24 adult male Wistar-Albino rats were equally and randomly divided into four groups as follows: group 1 (Controls), group 2 (Cabazitaxel 0.5mg/kg), group 3 (Cabazitaxel 1.0mg/kg) and group 4 (Cabazitaxel 1.5mg/kg). Cabazitaxel (Jevtana, Sanofi-Aventis USA) was intraperitoneally administered to groups 2, 3 and 4 at 0.5, 1.0 and 1.5mg/kg (body-weight/week) doses, respectively for four consecutive weeks. Beside this, group 1 received only i.p. saline at the same volume and time. At the end of the study, animals were sacrificed and bilateral brain hemispheres were removed for biochemical, histopathological and immunohistochemical examinations. RESULTS: Intraperitoneal administration of Cabazitaxel has exerted neurotoxic effect on rat brain. We have observed that biochemical and immunohistochemical results became worse in a dose dependent manner. CONCLUSION: Our findings have suggested that Cabazitaxel may be a neurotoxic agent and can trigger apoptosis in neuron cells especially at high doses.

Stereological and Morphometric Analysis of MRI Chiari Malformation Type-1.

OBJECTIVE: In this study, we aimed to investigate the underlying ethiological factors in chiari malformation (CM) type-I (CMI) via performing volumetric and morphometric length-angle measurements. METHODS: A total of 66 individuals [33 patients (20-65 years) with CMI and 33 control subjects] were included in this study. In sagittal MR images, tonsillar herniation length and concurrent anomalies were evaluated. Supratentorial, infratentorial, and total intracranial volumes were measured using Cavalieri method. Various cranial distances and angles were used to evaluate the platybasia and posterior cranial fossa (PCF) development. RESULTS: Tonsillar herniation length was measured 9.09±3.39 mm below foramen magnum in CM group. Tonsillar herniation/concurrent syringomyelia, concavity/defect of clivus, herniation of bulbus and fourth ventricle, basilar invagination and craniovertebral junction abnormality rates were 30.3, 27, 18, 2, 3, and 3 percent, respectively. Absence of cisterna magna was encountered in 87.9% of the patients. Total, IT and ST volumes and distance between Chamberlain line and tip of dens axis, Klaus index, clivus length, distance between internal occipital protuberance and opisthion were significantly decreased in patient group. Also in patient group, it was found that Welcher basal angle/Boogard angle increased and tentorial slope angle decreased. CONCLUSION: Mean cranial volume and length-angle measurement values significantly decreased and there was a congenital abnormality association in nearly 81.5 percent of the CM cases. As a result, it was concluded that CM ethiology can be attributed to multifactorial causes. Moreover, congenital defects can also give rise to this condition.

The effects of amlodipine and platelet rich plasma on bone healing in rats.

AIM: The aim of this study was to evaluate the effects of calcium channel blocker (CCB) amlodipine (AML), platelet rich plasma (PRP), and a mixture of both materials on bone healing. MATERIALS AND METHODS: Fifty-six male Wistar rats were randomly divided into four groups: group A, tibia defect model with no treatment; group B, tibia defect model treated with AML, 0.04 mg daily by oral gavage; group C, tibia defect model treated with local PRP; group D, tibia defect model treated with local PRP and AML, 0.04 mg daily by oral gavage. RESULTS: At day 21, bone healing was significantly better in groups C and D compared to group A (P<0.05), but comparisons showed no statistically significant difference in group B (P>0.05). At day 30, groups B and C showed no statistically significant difference (P>0.05) compared to group A, but bone healing in group D was significantly better than in group A (P<0.05). Statistically, AML did not affect alkaline phosphatase (ALP) activity at 21 and 30 days (P>0.05), but PRP and AML + PRP increased ALP activity statistically (P<0.05). CONCLUSION: It can be concluded that AML had neither a positive nor a negative effect on bone healing, but when used in combination with PRP, it may be beneficial.

Effect of IL-18 binding protein on hepatic ischemia-reperfusion injury induced by infrarenal aortic occlusion.

PURPOSE: Severe local and systemic tissue damage called ischemia/reperfusion (IR) injury occurs during the period of reperfusion. Free oxygen radicals and proinflammatory cytokines are responsible for reperfusion injury. IL-18 binding protein (IL-18BP) is a natural inhibitor of IL-18. The balance between IL-18 and IL-18BP has an important role in the inflammatory setting. The present study aimed to investigate whether IL-18BP had a protective role in remote organ hepatic IR injury. METHODS: Wistar-Albino rats were divided into three groups that contained seven rats. Group I (sham): Laparotomy and infrarenal abdominal aorta (AA) dissection were done but no clamping was done. Group II (I/R): The infrarenal AA was clamped by atraumatic microvascular clamp for 30 minutes and then was exposed to 90 minutes of reperfusion. Group III (IR + IL-18BP): 75 µg/kg of IL-18BP in 0.9% saline (1 mL) was administered 30 minutes before infrarenal AA dissection and clamping; 30 minutes of ischemia was applied and then was exposed to 90 minutes of reperfusion. RESULTS: Serum AST, ALT, and LDH levels were remarkably higher in IR group and returned to normal levels in treatment group. The proinflammatory cytokine levels had decreased in treatment group, and was statistically significant compared with the IR group. Serum levels of total oxidant status and oxidative stress index decreased and levels of total antioxidant status increased by IL-18BP. CONCLUSION: This study suggested that IL-18BP has antioxidant, anti-inflammatory and hepatoprotective effects in cases of IR with infrarenal AA induced liver oxidative damage.

Investigation of protective role of curcumin against paclitaxel-induced inner ear damage in rats.

OBJECTIVES/HYPOTHESIS: The aim of this study was to investigate the potential protective effect of curcumin on paclitaxel-induced ototoxicity in rats by means of immunohistochemical and histopathological analysis and distortion product otoacoustic emissions (DPOAEs). STUDY DESIGN: Animal study. METHODS: Forty Sprague-Dawley rats were randomized into five groups. Group 1 was administered no paclitaxel and curcumin during the study. Groups 2, 3, 4 and 5 were administered 5 mg/kg paclitaxel; 200 mg/kg curcumin; 5 mg/kg paclitaxel, followed by 200 mg/kg curcumin; 200 mg/kg curcumin and a day later 5 mg/kg paclitaxel followed intraperitoneally by 200 mg/kg curcumin once a week for 4 consecutive weeks, respectively. After the final DPOAEs test, the animals were sacrificed and their cochlea were prepared for hematoxylin and eosin and caspase-3 staining. RESULTS: The DPOAEs thresholds and histopathological and immunohistochemical findings were substantially correlated in all groups. The histopathologic findings in the cochlea of the paclitaxel-treated animals showed not only changes in the organ of Corti, but also damage to the stria vascularis and spiral limbus, including nuclear degeneration, cytoplasmic vacuolization, and atrophy of intermediate cells. Additionally, cochlear changes in group 2, such as intense apoptosis, were confirmed by caspase-3 immunohistochemical staining. In group 4, coreceiving curcumin could not sufficiently prevent paclitaxel-induced ototoxicity, and the results in group 5 were similar to the control group. CONCLUSIONS: In our study, we have concluded that pre- and coreceiving curcumin can significantly protect the cochlear morphology and functions on paclitaxel-induced ototoxicity in rats. Curcumin might be considered as a potential natural product that, used as a dietary supplement, could be easily given to patients undergoing paclitaxel chemotherapy. LEVEL OF EVIDENCE: NA