Evaluating the therapeutic effect of vitamin D and nerolidol on lung injury due to experimental myocardial infarction: The potential role of asprosin and spexin.

Injury to internal organs caused by myocardial infarction (MI), although often neglected, is a very serious condition which damages internal organs especially the lungs. Changes in microcirculation can begin with acute lung injury and result in severe respiratory failure. The aim of this study was to create new approaches that will explain the pathophysiology and treatment of the disease by examining the therapeutic effects of vitamin D (VITD) and Nerolidol (NRD) on the injuries of the lungs caused by MI, and their relationship with asprosin / spexin proteins. METHODS: Six groups of seven experimental animals each were constituted. Control, VITD (only 50 IU/day during the experiment), NRD (only 100 mg/kg/day during the experiment), MI (200 mg/kg isoproterenol was administered to rats as a single dose subcutaneously), MI+VITD (200 mg/kg isoproterenol +50 IU/day) and MI+NRD (200 mg/kg isoproterenol +100 mg/kg/day) were the six (6) groups constituted. Tissues were analyzed using histopathological and immunohistochemical methods, whereas serum samples were analyzed using ELISA method. RESULTS: The result of the histopathological study for the MI group showed an observed increase in inflammatory cells, congestion, interalveolar septal thickening, erythrocyteloaded macrophages and fibrosis in the lung tissues. The treatment groups however recorded significant differences with regards to these parameters. In the immunohistochemical analysis, expressions of asprosin and spexin were observed in the smooth muscle structures and interalveolar areas of the vessels and bronchioles of the lung, as well as the bronchiole epithelium. There was no significant difference between the groups in terms of asprosin and spexin expression in the bronchiol epithelium. When immunohistochemical and serum ELISA results were examined, it was observed that asprosin levels increased significantly in the lung tissues of the MI group compared to the control group, decreased significantly in the treatment groups treated with Vitamin D and NRD after MI. While spexin decreased significantly in the MI group compared to the control group, it increased significantly in the MI+VITD group, but did not change in the MI+NRD group. CONCLUSION: It was observed that serious injuries occurred in the lungs due to myocardial infarction and that, VITD and NRD treatments had a curative effect on those injuries. It was also observed that Asprosin and Speksin proteins can have effect on mechanisms of both injury and therapy of the lung. Furthermore, the curative effects of VITD are dependent on the expression of asprosin and spexin; whereas the observation indicated that nerolidol could be effective through asprosin-dependent mechanisms and specisin by independent mechanisms.

Role of asprosin and meteorin-like peptide in progression of actinic keratosis to squamous cell carcinoma.

Squamous cell carcinoma (SCC) often develops from an underlying premalignant lesion. Factors that affect the progression of actinic keratosis (AK) to invasive SCC are not fully known. Asprosin (ASP) and meteorin-like peptide (METRNL) are adipokines that are involved primarily in glucose metabolism. We investigated the expression of ASP and METRNL in AK and SCC to evaluate the role of these adipokines in the development of SCC. We used 15 SCC specimens, 12 AK specimens and 12 healthy control skin specimens. ASP and METRNL protein expression in tumor and surrounding tissue was evaluated using immunohistochemistry. ASP expression in tumor tissue was significantly greater in the SCC group than in the control and AK groups, but it did not differ significantly between the AK and control groups. A positive correlation was observed for both ASP and METRNL expressions between tumor tissue and adjacent epidermis, hair follicles, sebaceous gland, eccrine gland, inflammatory cells and vascular structures. ASP and METRNL may exert pro-tumor effects toward development of invasive SCC. The expression intensity of ASP and METRNL can be used as a biomarker of risk of progression to SCC.

The Role of Meteorin-Like Peptide and Asprosin in Colon Carcinoma.

INTRODUCTION:  Colon cancer is one of the most frequent gastrointestinal system cancers on a global scale. Common colonoscopy tests have reduced the incidence of colorectal cancer (CRC). Although nutrition, microorganisms, and their metabolites are related to colon cancer, the exact mechanism of CRC is still not clear. For this reason, it is of great importance to elucidate the molecular mechanisms of colon oncogenesis. METHODS: This study was conducted retrospectively with samples obtained from the laboratory of Firat University Faculty of Medicine, Department of Pathology. A total of 30 patient samples were used. The control group consisted of healthy colon tissues from the same patients, and the other group consisted of colon carcinoma tissues from the same patients. Tissue samples of both groups were evaluated immunohistochemically with meteorin-like (METRNL) peptide and Asprosin. RESULTS: The immunoreactivity of METRNL was found to be lower in colon carcinoma tissues than in healthy colon tissues (0.2 ± 0.06 and 0.08 ± 0.03, respectively). Asprosin immunoreactivity was found to be higher in colon carcinoma tissues than in healthy colon tissues (0.4 ± 0.07 and 1.08 ± 0.15, respectively). CONCLUSION: As a result of this study, it was observed that there was a significant difference between healthy colon tissue and colon carcinoma tissue in terms of METRNL and Asprosin expression. Both proteins might be involved in the molecular mechanism of colon carcinoma. This situation is important in terms of diagnosis.

The protective effects of humanin in rats with experimental myocardial infarction: The role of asprosin and spexin.

Objective: In this study, by applying humanin (HN) before myocardial infarction (MI) in rats, its protection in MI and the possible roles in asprosin and spexin were investigated. Materials and methods: The rats were divided into 7 groups each with 6 rats (group I (control), group II (HN 48th hour), group III (HN 7th day), group IV (MI 48th hour), group V (MI 7th day), group VI (MI + HN 48th hour), group VII (MI + HN 7th day). To create MI, 200 mg/kg isoproterenol (ISO) was administered subcutaneously to the rats. 2 mg/kg HN was given intraperitoneally (ip) to rats alone and before MI. Molecular parameters asprosin and spexin were examined by immunohistochemical in heart tissue. Biochemical parameters (aspartate aminotransferase (AST), lactate dehydrogenase (LDH), creatine kinase MB (CK-MB), Troponin I) were studied in serum by enzyme-linked immunosorbent assay (ELISA) method. Results: It was found in the study that the levels of spexin elevated especially towards the 7th day after MI and decreased more significantly towards the 7th day, after HN application before MI. Asprosin elevated significantly towards the 7th day after MI and decreased especially on the 7th day after HN application before MI. Also, serum AST, LDH, CK-MB, and Troponin I levels tended to decrease and a significant decrease was detected in congested veins in the heart tissue at the 48th hour of MI and erythrocyte extravasation, congested veins and necrotic muscle fibers at the 7th day of MI in rats given HN before MI. Conclusion: It was concluded that HN has a cardioprotective effect in MI and asprosin and spexin might mediate this effect.

The Effects of N-acetylcysteine on Transient Receptor Potential Melastatin 2 Channels Activation and Expression in Testicular Tissue of Diabetic Rats.

INTRODUCTION: Diabetes mellitus (DM) is a common, chronic metabolic disease that has harmful effects on many diverse tissues, including the testis. One of the ways of tissue damage is the modification of transient receptor potential melastatin 2 (TRPM2) channels by increased reactive oxygen species (ROS). In our study for the first time, it was aimed to investigate TRPM2 channel activation in testicular tissues of diabetic rats induced by streptozotosin (STZ) and to examine the efficacy of N-acetylcysteine (NAC) treatment, which is an antioxidant. METHODS: In our study, 28 Wistar albino male rats aged 8-10 weeks were used, and animals were divided into four groups: control group, NAC group, DM group, and DM + NAC group. The experimental phase was designed as eight weeks. The malondialdehyde (MDA) level, which is an indicator for lipid peroxidation due to oxidative stress, was measured by the spectrophotometric method. The Tunel assay was used to determine apoptosis on testicular tissue. TRPM2 immunoreactivity was determined by the avidin-biotin-peroxidase complex method, and quantitative polymerase chain reaction (QPCR) was used to determine TRPM2 expression levels. RESULTS: It was seen that MDA levels were significantly increased in the DM group and decreased after NAC treatment. Similarly, it was observed that apoptosis levels, which increased significantly in diabetic rats, decreased to the levels of the control group after treatment. It was seen that TRPM2 activation and expression levels were significantly decreased in the DM group. CONCLUSION:  The results of this study show that NAC regulates TRPM2 activation in the testicular tissue of patients with diabetes and has tissue-protective properties.

A rare but very serious disease: Tumors metastasizing to the thyroid in the light of cases.

INTRODUCTION: Metastasis to the thyroid gland is a rare condition that can pose diagnostic difficulties. The purpose of the present study was to provide an overview of non-thyroid tumors metastasizing to the thyroid based on our institutional experience. MATERIAL AND METHOD: The data of the study were obtained by using the pathology database investigating patients diagnosed with tumor metastasis to° the thyroid between 2013 and 2022 at Firat University Hospital and reviewing their medical files. RESULTS: As a result of histochemical and immunohistochemical examinations of the thyroid, seven patients were diagnosed with tumor metastasis. Of the seven patients, 3 (42.85%) were female and 4 (57.14%) were male. The median age at which thyroid metastases were detected was 60.71 (52-80). The most common metastatic thyroid tumors of primary origin were kidney (28.5%), lung (28.5%), head and neck malignancies (28.5%) and unknown primary tumors (14.5%). The median time from diagnosis of primary tumor to diagnosis of thyroid metastasis was 26 months (12-36). The longest survival was determined in clear cell renal cell carcinoma, and the shortest survival was determined in lung cancer. CONCLUSION: Thyroidal metastases are rare; however, they must be suspected in patients with a previous history of non-thyroid malignancy and a thyroid nodule. The prognosis is quite poor and the overall survival of the patient depends on the type and location of the primary tumor. The most common primary tumors metastasizing to the thyroid are kidney, lung, and head and neck malignancies, and surgery/chemotherapy may be beneficial.

New candidates in the differential diagnosis of malignant mesothelioma from benign mesothelial hyperplasia and adenocarcinoma; DARS2 and suprabasin.

OBJECTIVES: Malignant mesothelioma (MM) is a primary malignant tumour with a very bad prognosis, which develops from the mesothelial cells lining the serosal surfaces. Because MM can show a wide variety of histological patterns and its cytomorphological features are quite extensive, it is often confused with lung adenocarcinomas (LAC) and reactive mesothelial hyperplasia (RMH). The immunohistochemical examination method is the most useful method for discrimination. In this study, we aimed to determine the value of suprabasin and DARS2 markers in the differential diagnosis of RMH, MM and LAC. METHODS: Thirty MM, 30 LAC and 30 RMH samples selected from the archive of Firat University Hospital Pathology Department Laboratory were included in this study. Suprabasin and DARS2 markers were applied to the samples immunohistochemically and their place in the differential diagnosis was examined. RESULTS: Although DARS2 expression was observed in RMH, MM and adenocarcinoma samples, Suprabasin expression was only observed in adenocarcinoma. There was a significant difference between the groups in terms of DARS2 and Suprabasin expression. No suprabasin expression was detected in MM and RMH. CONCLUSION: Suprabasin and DARS2 may be proposed as new biomarkers to differentiate MM from LAC.

Role of suprabasin, a new biomarker in squamous cell carcinoma and basal cell carcinoma.

INTRODUCTION: Suprabasin is a newly discovered protein linked to various human diseases including cancer. It may does have an effect on the development and expression of some non-melanoma skin cancers such as basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). BCC is the most common non-melanoma skin cancers worldwide, while SCC comes as the second in terms of prevalence. In certain cases, it is very important to distinguish between these two carcinomas from each other and from normal skin samples. This study was aimed at investigating the characteristics of suprabasin expression in squamous cell carcinoma and basal cell carcinoma and whether it can be used as a biomarker. MATERIALS AND METHODS: Thirty control, ninety SCC and thirty BCC cases obtained from the archives of the Department of Pathology, Faculty of Medicine, Firat University, were examined by immunohistochemical staining for suprabasin. RESULTS: Increased suprabasin expression was observed in tumour tissues and normal skin samples in SCC. As the grade increased in SCC, suprabasin expression decreased. No suprabasin expression was observed in the lesion area in BCC. CONCLUSION: Suprabasin can be reported as a biomarker for SCC and used to differentiate SCC from BCC. Expression of suprabasin in SCC can be used to determine grade. Absence of suprabasin expression in BCC can be used for differential diagnosis.

Two Novel Biomarker Candidates for Differentiating Basal Cell Carcinoma from Trichoblastoma; Asprosin and Meteorine Like Peptide.

INTRODUCTION: BCC (Basal Cell Carcinoma) and trichoblastoma are skin tumors originating from the hair follicle. BCC is the most common non-melanoma skin cancer. Differential diagnosis of BCC from trichoblastoma, which is a common benign tumor in terms of histology, morphology, and immunohistochemistry, is not possible. The effects of adipokines on tumorigenesis have attracted attention. MATERIALS AND METHODS: By examining the effects of Asprosin and Meteorine like peptide (METRNL) on these tumors, it is aimed to reach new information in the differential diagnosis of BCC and trichoblastoma. Twenty normal healthy tissue, 17 basal cell carcinoma and 12 trichoblastoma samples were included in the study. RESULTS: Increased expression of Asprosin and METRNL was observed in tumor and stromal tissues in BCC. Although overexpression of METRNL was observed in the lesion area in trichoblastoma, no increase in Asprosin expression was observed. Asprosin and METRNL immunoreactivity were found to be statistically significantly higher in BCC samples compared to control and trichoblastoma. CONCLUSION: Asprosin and METRNL can be used in the diagnosis of BCC. METRNL can be used in the diagnosis of trichoblastoma. These biomarkers are helpful for differentiation between BCC and trichoblastoma.

Effects of Carnosine, Ankaferd, and Silver Sulfadiazine on an Experimental Burn Model: Roles of Irisin and HSP70.

In this study, the effects of carnosine, ankaferd, and 1% silver sulfadiazine applied topically on second-degree burns were investigated and the roles of irisin and Heat shock protein 70 (HSP70) in this healing process were evaluated. Ninety male albino rats were used and divided into five groups. The groups were classified as control, burn, burn + carnosine (CAR), burn + ankaferd (ABS), and burn + silver sulfadiazine (SS). It was found that level of irisin increased in the first week and decreased in the second week in the burn and CAR groups. In the ABS and SS groups, the level of irisin was determined that started to increase in the first week and continued to increase in the second week. The level of HSP70 was found to increased in the first week in burn and CAR groups and decreased in the second week, but started to increase in the second week in ABS and SS groups. Both levels of irisin and HSP70 were observed to decreased in all treatment groups in the third week. In this study, it was shown that ankaferd and silver sülfadiazine treatments cause an increase in the irisin levels in the early period and a gradually increase in HSP70 levels in the later period in burns. The inflammatory response was observed to be limited in the early period in the ankaferd and sulfadiazin groups. It was concluded that these findings were effective in early wound healing in burns.

Expression of asprosin in rat hepatic, renal, heart, gastric, testicular and brain tissues and its changes in a streptozotocin-induced diabetes mellitus model.

In this study, we aimed to investigate the presence of asprosin (ASP) in the liver, kidneys, heart, stomach, testicles and brain and to determine the serum and tissue asprosin levels in diabetic rats. A total of 14 male Wistar Albino rats were divided into two groups, each containing 7 rats: (I) control group and (II) experimental diabetes group. Control rats received no treatment and the rats in the experiment group received single-dose of streptozotocin (STZ) (50 mg/kg) dissolved in 0.1 M sodium citrate buffer (pH: 4.5) intraperitoneally. Serum levels of asprosin were measured using ELISA method. The presence of asprosin in hepatic, renal, cardiac, gastric, testicular and brain tissues was investigated using immunohistochemical staining. Asprosin was detected in hepatocytes in the liver, cortical distal tubule cells in the kidney, cardiomyocytes in heart, surface epithelial cells of stomach fundus, interstitial Leydig cells in testes and cortical neurons of the brain. Compared to control group, it was found that diabetic rats had decreased asprosin levels in liver, kidney and heart tissues, increased levels in gastric and testicular tissues and no significant changes in brain tissue. Serum asprosin levels of diabetic rats were found to be decreased compared to the control group. This is the first study in the literature that reports the presence of asprosin in liver, kidney, heart, stomach, testis and brain tissues in rats. The aim of the study is to determine the presence of ASP, a newly discovered adipokine, in various tissues and to examine tissue and serum level changes in STZ-induced diabetes.

The protective effect of resveratrol against risperidone-induced liver damage through an action on FAS gene expression.

The purpose of the study is to examine the protective effect of resveratrol on the fatty acid synthase gene expression against the side-effects of risperidone in an experimental model in rat liver. In this study, thirty-five female Spraque-Dawley rats were divided into five groups (n = 7): Control, RIS (2 mg/kg risperidone daily), RSV1 (2 mg/kg risperidone + 20 mg/kg resveratrol), RSV2 (2 mg/kg risperidone + 40 mg/kg resveratrol), and RSV3 group (2 mg/kg risperidone + 80 mg/kg resveratrol). On treatment day 15, liver tissue was taken for analysis. The resveratrol treatment significantly reduced weight gain as opposed to the risperidone administration. Moreover, the fatty acid synthase gene expression level increased significantly in RSV1 group (p = 0.011). In addition, resveratrol enhanced the total antioxidant status, high-density lipoprotein cholesterol levels and decreased alanine aminotransferase, aspartate aminotransferase, total cholesterol, gamma glutamyl transpeptidase, low density lipoprotein cholesterol, oxidative stress index, triglycerides, and total oxidant status levels significantly (p < 0.05). In conclusion, this study revealed that treatment with resveratrol might protect liver tissue against the side--effects of risperidone over fatty acid synthase gene expression. Resveratrol could be an effective course of therapy for enhancing therapeutic efficacy.

Magnesium: does it reduce ischemia/reperfusion injury in an adnexal torsion rat model?

AIM: The aim of the present study was to assess the protective effects of magnesium sulfate (MgSO4) on ischemia/reperfusion (I/R) induced ovarian damage in a rat ovarian torsion model. METHODS: Forty-two female Sprague Dawley rats were included in the study. They were divided into six groups as Group 1, sham; Group 2, bilateral ovarian torsion; Group 3, bilateral ovarian torsion-detorsion; Group 4, MgSO4-sham; Group 5, MgSO4-bilateral ovarian torsion; Group 6, bilateral ovarian torsion-MgSO4-detorsion. Both torsion and detorsion periods lasted 3 hours. In Groups 4, 5 and 6, MgSO4 (600 mg/kg) was administered by intraperitoneal route 30 minutes before sham operation, torsion and detorsion, respectively. At the end of the study period, both ovaries were removed. One of the ovaries was used for histopathological analyses and the other for biochemical analyses. RESULTS: In the torsion-detorsion group, all the histopathological scores were higher compared to the sham and torsion only group (p<0.05). Administration of MgSO4 only caused significant decrease in the inflammatory cell scores of the torsion-detorsion group (p<0.05). MgSO4, whether given before torsion or before detorsion, suppressed malondialdehyde levels when compared to the untreated groups (p<0.01 and p<0.001, respectively). Glutathione peroxidase activities were significantly higher in the MgSO4 applied torsion and detorsion groups than Groups 2 and 3 (p<0.05, for both). Administration of MgSO4 also caused an increase in glutathione levels in the torsion and detorsion groups compared to the torsion only and detorsion only groups (p<0.05, for both). Also, total oxidant status levels decreased in the MgSO4 applied torsion and detorsion groups compared to the untreated corresponding ones (p<0.01 and p<0.001, respectively). MgSO4 significantly decreased the Oxidative Stress Index levels in the torsion-detorsion group compared to Group 2 (p<0.001). CONCLUSION: Histopathological and biochemical analysis revealed that prophylactic treatment with MgSO4 reduces the changes observed in I/R injury in a rat model.

Risperidone-Induced Renal Damage and Metabolic Side Effects: The Protective Effect of Resveratrol.

OBJECTIVE: The aim of the study was to investigate the possible protective qualities of resveratrol (RSV) against the side effects of risperidone (RIS) in an experimental model in rat kidneys with histologic and biochemical assessments. MATERIALS AND METHODS: Experimental procedures were performed on 35 female Sprague Dawley rats. Rats were randomly divided into five groups: control, untreated rats (n = 7) were in group 1; group 2 was given 2 mg/kg/day RIS (n = 7); group 3 was treated with 2 mg/kg/day RIS and 20 mg/kg/day RSV (n = 7); group 4 was treated with 2 mg/kg/day RIS and 40 mg/kg/day RSV (n = 7); and group 5 was treated with 2 mg/kg/day RIS and 80 mg/kg/day RSV (n = 7). All treatments were administered for two weeks by gavage. On treatment day 15, kidney tissues were removed for analysis. RESULTS: The results showed that RSV treatment reduced weight gain induced by RIS. In addition, RSV increased the total antioxidant status (TAS) and decreased serum creatinine (Cr), blood urea nitrogen (BUN), oxidative stress index (OSI), and total oxidant status (TOS) levels significantly (p < 0.05). CONCLUSION: This study revealed that treatment with RSV might protect kidney tissues against the side effects of RIS. RSV could be an effective course of therapy to enhance therapeutic efficacy.

Protective effects of vitamin D3 against d-galactosamine-induced liver injury in rats.

In this study, we examined liver damage induced by d-galactosamine (d-GaIN) and the protective effects of vitamin D3 in relation to d-GaIN toxicity. Twenty Wistar albino rats were used in this study. The rats were divided into four groups. Group I rats were used as the control group. Group II rats were given a single intraperitoneal injection of d-GaIN. Group III rats were given a single intraperitoneal injection of d-GaIN, intramuscular vitamin D3 for five days. Group IV rats were given intramuscular vitamin D3 for five days. All of rats were euthanized by cervical decapitation on the fifth day of experiment. Upon completion of the experiment, a midsaggital incision was performed, and the livers of all rats were removed and fixed. The livers were processed to perform TUNEL technique and histochemical staining. During the microscope examination, we observed inflamatory cell infiltration, sinusoidal dilatation, and apoptotic bodies due to d-GaIN exposure. In addition, glycogen content of the group II hepatocytes was significantly decreased. Vitamin D3 treatment provided better structural apperance of the livers in group III. TUNEL positive cells were extremly pervasive in the group II livers. The study found group III TUNEL positive cells at a reduced rate in relation to group II due to vitamin D3 treatment. This findings indicate that d-GaIN causes inflamation in the liver. This inflamation triggers the apoptotic process gradually. Vitamin D3 has potency to decrease the severity of d-GaIN-caused structural liver damage.

Effect of Caffeic Acid Phenethyl Ester on Vascular Damage Caused by Consumption of High Fructose Corn Syrup in Rats.

Fructose corn syrup is cheap sweetener and prolongs the shelf life of products, but fructose intake causes hyperinsulinemia, hypertriglyceridemia, and hypertension. All of them are referred to as metabolic syndrome and they are risk factors for cardiovascular diseases. Hence, the harmful effects of increased fructose intake on health and their prevention should take greater consideration. Caffeic Acid Phenethyl Ester (CAPE) has beneficial effects on metabolic syndrome and vascular function which is important in the prevention of cardiovascular disease. However, there are no known studies about the effect of CAPE on fructose-induced vascular dysfunction. In this study, we examined the effect of CAPE on vascular dysfunction due to high fructose corn syrup (HFCS). HFCS (6 weeks, 30% fed with drinking water) caused vascular dysfunction, but treatment with CAPE (50 micromol/kg i.p. for the last two weeks) effectively restored this problem. Additionally, hypertension in HFCS-fed rats was also decreased in CAPE supplemented rats. CAPE supplements lowered HFCS consumption-induced raise in blood glucose, homocysteine, and cholesterol levels. The aorta tissue endothelial nitric oxide synthase (eNOS) production was decreased in rats given HFCS and in contrast CAPE supplementation efficiently increased its production. The presented results showed that HFCS-induced cardiovascular abnormalities could be prevented by CAPE treatment.

Effects of silymarin on methotrexate-induced nephrotoxicity in rats.

Methotrexate (MTX) is widely used in the treatment of various malignancies and nononcological diseases but its use has been limited by its nephrotoxicity. Silymarin (SLY), a natural flavonoid, has been reported to have antioxidant, anti-inflammatory and anti-apoptotic effects. This study was carried out to determine whether SLY exerts a protective effect against MTX-induced nephrotoxicity. Rats were divided into six groups: Group 1 (saline, i.p., single injection), Group 2 (0.5% carboxymethyl cellulose (CMC), by gavage once daily for five consecutive days), Group 3 (SLY, 300 mg/kg per day, i.p. for five consecutive days), Group 4 (MTX, 20 mg/kg, i.p., single injection), Group 5 (MTX + CMC similarly as groups 2 and 4) and Group 6 (MTX + CMC + SLY similarly as groups 2, 3 and 4). Histopathologic alterations including apoptotic changes of the kidney were evaluated. MTX injection exhibited dilated Bowman's space, inflammatory cell infiltration, glomerular and peritubular vascular congestion and swelling of renal tubular epithelium cells. Apoptotic cell death was also markedly increased in renal tubules after MTX administration. SLY treatment resulted in statistically significant amelioration in the histological alterations and reduced the number of TUNEL-positive cells as compared with the MTX treated rats (p < 0.05). In conclusion, SLY treatment leads to a reduction on MTX-induced renal damage in rats. Since SLY is safe and acceptable for human consumption, further studies to define the exact mechanism of the protecting effect of SLY on MTX-induced nephrotoxicity and the optimum dosage of this compound would be useful.

Impact of intracystic ethanol instillation on ovarian cyst diameter and adjacent ovarian tissue.

OBJECTIVE: To investigate the regression level of simple ovarian cyst size after local ethanol application and the damage level of adjacent ovarian reserve in rats. STUDY DESIGN: This study was conducted at Firat University Animal Laboratory with 18 mature (12-14 weeks old) female Wistar albino rats weighing 200-220g, with regular cycles. Ovarian cyst induction was performed with unilateral salpingectomy. Fourteen rats with ovarian cysts after a second laparotomy were divided into two groups as follows: Group 1 (n=7): cyst aspiration group, and Group 2 (n=7): intracystic 95% ethanol application group. One month after the cyst aspiration procedure a third laparotomy was performed. The cyst number and size were recorded for each rat. Right ovariectomy was performed and formalin-fixed/paraffin-embedded tissues were sectioned at 5µm thickness. Under light microscopy, ovarian total follicle reserve and fibrosis were evaluated with Masson trichrome staining and apoptosis was evaluated with TUNEL staining. The groups were compared with the Mann-Whitney U test and Wilcoxon Rank test. p<0.05 was considered significant. RESULTS: Ovarian cyst formation was observed in 85% (15/18) of rats. The mean diameter of ovarian cysts in Groups 1 and 2 were, respectively, 10.3mm and 10.1mm. After aspiration, there was no significant reduction in the cyst diameter (10.3mm vs 8.1mm), but after ethanol application the diameter significantly reduced (10.1mm vs 3.4mm, p<0.05). Mean ovarian follicle count in Group 2 was significantly lower than in Group 1 (25 vs 42, p<0.05), and mean fibrosis and apoptosis scores in Group 2 were significantly higher than in Group 1 (2.5 vs 0.9, p<0.05). CONCLUSION: Local ethanol application reduces cyst diameter but concomitantly decreases ovarian reserve due to increased fibrosis in rats. In humans, intracystic ethanol application should be performed cautiously.

Expression of adropin in rat brain, cerebellum, kidneys, heart, liver, and pancreas in streptozotocin-induced diabetes.

We have investigated how diabetes affects the expression of adropin (ADR) in rat brain, cerebellum, kidneys, heart, liver, and pancreas tissues. The rats in the diabetic group were administered an intraperitoneal (i.p.) injection of a single dose of 60 mg/kg streptozotocin (STZ) dissolved in a 0.1 M phosphate-citrate buffer (pH 4.5). The rats were maintained in standard laboratory conditions in a temperature between 21 and 23 °C and a relative humidity of 70 %, under a 12-h light/dark cycle. The animals were fed a standard commercial pellet diet. After 10 weeks, the animals were sacrified. ADR concentrations in the serum and tissue supernatants were measured by ELISA, and immunohistochemical staining was used to follow the expression of the hormones in the brain, cerebellum, kidneys, heart, liver, and pancreas tissues. The quantities were then compared. Increased ADR immunoreaction was seen in the brain, cerebellum, kidneys, heart, liver, and pancreas in the diabetes-induced rats compared to control subjects. ADR was detected in the brain (vascular area, pia mater, neuroglial cell, and neurons), cerebellum (neuroglial cells, Purkinje cells, vascular areas, and granular layer), kidneys (glomerulus, peritubular interstitial cells, and peritubular capillary endothelial cells), heart (endocardium, myocardium, and epicardium), liver (sinusoidal cells), and pancreas (serous acini). Its concentrations (based on mg/wet weight tissues) in these tissues were measured by using ELISA showed that the levels of ADR were higher in the diabetic rats compared to the control rats. Tissue ADR levels based on mg/wet weight tissues were as follows: Pancreas > liver > kidney > heart > brain > cerebellar tissues. Evidence is presented that shows ADR is expressed in various tissues in the rats and its levels increased in STZ-induced diabetes; however, this effect on the pathophysiology of the disorder remains to be understood.

The apoptotic effect of a high dose of toluene on liver tissue during the acute phase: an experimental study.

The aim of this study is to investigate the acute toxic effects of high-dose toluene and its mechanisms on the liver tissue of toluene-treated rats. In this study, 16 adult male Wistar albino rats (200-220 g) were divided into two equal groups. Group I was used as a control group, while group II was exposed to high dose of toluene, 5200 mg/kg (6 ml/kg per gavage). After the 3-hour experimental period, blood samples and liver tissues were taken from the euthanized animals. Serum aspartate and alanine aminotransferase levels were assayed. Liver tissues were fixed in 10% neutral formalin, then embedded in paraffin and sectioned (5 µm thickness). Sections were stained with hematoxylin and eosin for histopathological examination. A terminal transferase dUTP nick end labeling assay was also done for the determination of apoptosis in liver tissues. For the determination of Bax and caspase-3 immunoreactivity, the sections were stained using avidin-biotin-peroxidase immunohistochemical method. The level of plasma transaminase was found to be increased in toluene administered rats. Additionally, slight degeneration of hepatocyte and mononuclear cell infiltration was observed in the liver tissue sections and a high (+++) immunoreactivity for Bax and caspase-3 protein was observed in the toluene group. This study showed that the high dose of toluene triggers apoptosis in the liver of rats via the mitochondrial pathway in acute period.