Ferah Okkay, Irmak; Okkay, Ufuk; Cicek, Betul; Karatas, Ozhan; Yilmaz, Aysegul; Yesilyurt, Fatma; Hacimuftuoglu, Ahmet

The purpose of this study was to evaluate the effects of syringic acid, an anti-oxidant, on indomethacin induced gastric ulcers in rats. Experimental groups were control, ulcer, ulcer treated with 20 mg/kg esomeprazole (a proton pump inhibitor that reduces acid secretion), and ulcer treated with 100 mg/kg syringic acid. Rats were pretreated with esomeprazole or syringic acid two weeks before ulcer induction. Our histopathological observations showed that either syringic acid or esomeprazole attenuated the severity of gastric mucosal damage. Moreover, syringic acid and esomeprazole pretreatments alleviated indomethacin-induced damage by regulating oxidative stress, inflammatory response, the level of transforming growth factor-β (TGF-β), expressions of COX and prostaglandin E2, cell proliferation, apoptosis and regulation of the NF-κB signaling pathway. We conclude that either esomeprazole or syringic acid administration protected the gastric mucosa from harmful effects of indomethacin. Syringic acid might, therefore be a potential therapeutic agent for preventing and treating indomethacin-induced gastric damage.

Aydin, Suna; Kilinc, Faruk; Ugur, Kader; Aydin, Mustafa Ata; Yalcin, Mehmet Hanifi; Kuloglu, Tuncay; Kaya Tektemur, Nalan; Albayrak, Serdal; Emre, Elif; Yardim, Meltem

Metabolic syndrome (MetS) is a prevalent public health problem. Uric acid (UA) is increased by MetS. We investigated whether administration of UA and 10% fructose (F) would accelerate MetS formation and we also determined the effects of irisin and exercise. We used seven groups of rats. Group 1 (control); group 2 (sham); group 3 (10% F); group 4 (1% UA); group 5 (2% UA); group 6 (10% F + 1% UA); and Group 7, (10% F + 2% UA). After induction of MetS (groups 3 -7), Group 3 was divided into three subgroups: 3A, no further treatment; 3B, irisin treatment; 3C, irisin treatment + exercise. Group 4, 1% UA, which was divided into three subgroups: 4A, no further treatment; 4B, irisin treatment; 4C, Irisin treatment + exercise. Group 5, 2% UA, which was divided into three subgroups: 5A, no further treatment; 5B, irisin treatment; 5C, irisin treatment + exercise. Group 6, 10% F + 1% UA, which was divided into three subgroups: 6A, no further treatment; 6B, irisin treatment; 6C, irisin treatment + exercise. Group 7, 10% F + 2% UA, which was divided into three subgroups: 7A, no further treatment; 7B, irisin treatment; 7C, irisin treatment + exercise., İrisin was administered 10 ng/kg irisin intraperitoneally on Monday, Wednesday, Friday, Sunday each week for 1 month. The exercise animals (in addition to irisin treatment) also were run on a treadmill for 45 min on Monday, Wednesday, Friday, Sunday each week for 1 month. The rats were sacrificed and samples of liver, heart, kidney, pancreas, skeletal muscles and blood were obtained. The amounts of adropin (ADR) and betatrophin in the tissue supernatant and blood were measured using an ELISA method. Immunohistochemistry was used to detect ADR and betatrophin expression in situ in tissue samples. The duration of these experiments varied from 3 and 10 weeks. The order of development of MetS was: group 7, 3 weeks; group 6, 4 weeks; group 5, 6 weeks; group 4, 7 weeks; group 3, 10 weeks. Kidney, liver, heart, pancreas and skeletal muscle tissues are sources of adropin and betatrophin. In these tissues and in the circulation, adropin was decreased significantly, while betatrophin was increased significantly due to MetS; irisin + exercise reversed this situation. We found that the best method for creating a MetS model was F + UA2 supplementation. Our method is rapid and simple. Irisin + exercise was best for preventing MetS.

Huyut, Zübeyir; Uçar, Bünyamin; Yıldızhan, Kenan; Altındağ, Fikret; Huyut, Mehmet Tahir

This study investigated whether abemaciclib (ABE) administration had any adverse effects on ovarian and sex hormones in female rats, and the protective effect of curcumin. Forty female rats were equally divided into the sham control, DMSO, curcumin (CMN), ABE, and ABE+CMN groups. Pharmaceuticals were administered by gavage daily for 28 days. Serum sex hormones were measured in an autoanalyzer operating with a microparticle immunoassay method. In addition, histopathological examination and 8-OHdG expression were performed on the ovarian tissue. Progesterone and testosterone levels were significantly decreased, while estradiol levels were significantly increased, in the ABE group compared to the sham and DMSO groups. In addition, there were significant differences in sex hormone levels in the CMN and/or CMN+ABE groups compared to the ABE group. There was decreased expression of 8-OHdG in the ABE+CMN group compared to the ABE or CMN only groups. This study exhibited that ABE administration can adversely affect functions and histology of the ovarian tissue, but CMN therapy may be protective against the adverse effects on ovarian in ABE-induced rats.

Mirzaoglu, Miyase; Yavuzkir, Seyda; Mirzaoglu, Cetin; Yurt, Nurdan; Dagli, Adile Ferda; Ozcan Yildirim, Sena; Sahin, İbrahim; Aydin, Suleyman

Asprosin (ASP) and subfatin are hormones that regulate glucose metabolism. The role of ASP and subfatin in serous ovarian tumors has not been investigated. We investigated the expression of subfatin and asprosin in 30 serous benign, 30 serous borderline, 30 malignant and 30 control ovarian tissues. We investigated ASP and subfatin immunoreactivity and quantification was achieved using an ELISA method. ASP and subfatin were localized in the epithelial parts of normal ovarian tissues; however, in cancer tissues, immunoreactivity was detected in the parenchymal areas. Biochemical analysis of ovarian tissues revealed significantly decreased ASP and subfatin compared to the control. We propose that ASP and subfatin are promising candidates for biomarkers to distinguish serous benign, serous borderline and malignant ovarian cancers.

Yıldırım, Erkan; Yıldırım, Nilgun; Cengiz, Mahir; Yazıcı, Gulce Naz; Coskun, Resit; Suleyman, Bahadır; Coban, Abdulkadir; Suleyman, Halis

Bevacizumab is a recombinant humanized monoclonal antibody whose adverse effects include cardiotoxicity. We investigated whether using adenosine triphosphate (ATP) or benidipine either separately or together protects against cardiac damage induced by bevacizumab in rats. Forty Wistar albino male rats were allocated to five groups of eight: bevacizumab (Bv), ATP + bevacizumab (ABv), benidipine + bevacizumab (BBv), ATP + benidipine + bevacizumab (ABBv) and untreated controls. Rats in the ABv group were injected intraperitoneally (i.p.) with 2 mg/kg ATP. The BBv group was given 4 mg/kg benidipine by oral gavage. The ABBv group was injected i.p. with 2 mg/kg ATP and simultaneously administered 4 mg/kg benidipine orally. One hour after administration of ATP, benidipine or normal saline, the Bv, ABv, BBv and ABBv groups were injected i.p. with 10 mg/kg bevacizumab. Malondialdehyde (MDA) and total glutathione (tGSH) levels were measured in cardiac tissue, and troponin I (TP I) and creatine kinase MB (CK-MB) levels were measured in blood samples. Tissue samples were examined for histopathology. We found the lowest TP I, CK-MB and MDA levels and the highest tGSH level in the ABBv group; these results were similar to the control group. Nuclei of cardiomyocytes in the BV group were misshapen and shrunken, and myofibers were disrupted; we also observed eosinophilic degeneration and interstitial edema. Blood capillaries were dilated and congested. We observed amelioration of these findings in the ABBv group. We found that ATP and benidipine alone or in combination reduced cardiac damage associated with the use of bevacizumab. ATP + benidipine combined therapy produced the most favorable results.

Yavuz, Adem; Aydin, Mustafa Ata; Ugur, Kader; Aydin, Suna; Senol, Arzu; Baykus, Yakup; Deniz, Rulin; Sahin, İbrahim; Yalcin, Mehmet Hanifi; Gencer, Berrin Tarakci

We investigated the presence of asprosin (ASP), betatrophin, elabela (ELA), glucagon and subfatin (SUB) in the milk of mothers with gestational diabetes mellitus (GDM) and compared their levels with blood levels. We also investigated whether these peptides are synthesized by the breast. We investigated 12 volunteer mothers with GDM and 14 pregnant non-GDM control mothers. The peptides were measured using ELISA and their tissue localization was determined using immunohistochemistry. Breast milk contains ASP, betatrophin, ELA, glucagon and SUB. The amount of the peptides ranged from highest to the lowest in colostrum, transitional milk and mature milk. The amount of peptides in the milk was greater than for blood. The peptides, except for ELA, were increased in milk and blood by GDM. Betatrophin and ELA are synthesized in the connective tissue of the breast. ASP, glucagon and SUB are synthesized in the alveolar tissue of the breast. These peptides in breast milk may contribute to the development of the gastrointestinal tract of newborns and infants.

Çolak, Suat; Koc, Kubra; Yıldırım, Serkan; Geyikoğlu, Fatime

We investigated the role of boric acid (BA) in ovarian tissue damage caused by ischemia/reperfusion (I/R) in the rat. We established four groups of seven adult female rats: untreated control; ovarian I/R; 15 mg/kg BA; I/R + 15 mg/kg BA. Ovarian levels of lipid peroxidase (LPO), myeloperoxidase (MPO), glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) and interleukin-6 (IL-6) were measured biochemically. Ovaries were evaluated for histopathology and investigated using immunohistochemistry. We detected greater LPO activity and less CAT, SOD and GSH levels in the I/R groups compared to the control group. LPO and MPO levels in ovarian samples for the I/R goup were increased significantly compared to untreated controls. The levels of LPO and MPO in ovarian tissue for the I/R + BA group were not significantly different from controls. SOD and GSH activity in ovarian tissue was increased significantly compared to controls. We found degenerated parenchymal cells, hemorrhage, necrotic parenchyma cells and congestion in the I/R groups. Expression of 8-OHdG was greater in the I/R group than in controls. Although immunostained cells were dense in the ovarian tissue in the I/R group, the number of immunostained cells was decreased by application of BA to the I/R group. BA exhibits a protective effect on ovarian tissue against I/R damage in the rat.

Yildirim, Nilgun; Lale, Azmi; Yazıcı, Gulce Naz; Sunar, Mukadder; Aktas, Mehmet; Ozcicek, Adelet; Suleyman, Bahadır; Ozcicek, Fatih; Suleyman, Halis

Hepatotoxicity is a common side effect of doxorubicin (Dox) treatment of cancer. Liv-52 is an ayurvedic medicine that is reported to ameliorate liver injury due to oxidative stress. We investigated the effects of Liv-52 on Dox induced oxidative damage to liver tissues of rats using biochemical and histopathological techniques. Thirty male rats were assigned randomly into three equal groups: control (CG), Dox group (DG) Liv-52 + Dox group (LD). Rats in the LD group received 50 mg/kg Liv-52 in distilled water via gastric gavage. Distilled water was given via the same route to the rats in the DG and CG groups. Rats in the LD and DG groups were injected intraperitoneally with 5 mg/kg Dox 1 h after administration of Liv-52 or distilled water. The procedure was repeated daily for 7 days. On day 8, the animals were sacrificed, and serum and tissue biochemical and histopathological assays were performed. The malondialdehyde level was increased significantly in the DG group, while glutathione and superoxide dismutase levels were significantly lower in the DG group compared to the LD and CG groups. The highest levels of alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase were found in the DG group, while the lowest levels were found in the CG group, which exhibited levels similar to those of the LD group. Treatment with Liv-52 prior to Dox treatment reduced the histopathologic changes in the Dox group. Therefore, pre-treatment with Liv-52 protected against Dox induced oxidative stress and hepatotoxicity.

Akkoc, R.F.; Aydin, S.; Goksu, M.; Ozcan Yildirim, S.; Eroksuz, Y.; Ogeturk, M.; Ugur, K.; Dagli, A.F.; Yakar, B.; Sahin, İ.

Renalase (RNLS) is synthesized mainly in renal tissues. The function of RNLS in cancerous renal tissues has not been investigated. We investigated the synthesis of RNLS in chromophobe renal cell carcinoma, papillary renal cell carcinoma and clear cell renal cell carcinoma with Fuhrman grades (FG): FG1, nucleoli are absent or inconspicuous and basophilic; FG2, nucleoli are conspicuous and eosinophilic and visible but not prominent; FG3, nucleoli are conspicuous and eosinophilic; FG4, extreme nuclear pleomorphism, multinucleate giant cells, and/or rhabdoid and/or sarcomatoid differentiation. We used 90 tissue samples including 15 healthy controls, 15 chromophobe renal cell carcinoma tissues and 10 papillary renal cell carcinoma renal tissues: 12 FG1, 14 FG 2, 14 FG 3 and 10 FG4. RNLS in the tissue samples was measured using enzyme linked immunosorbent assay and immunostaining of RNLS in these tissues. RNLS was significantly greater in the chromophobe renal cell carcinoma and papillary renal cell carcinoma tissues than the control. The least amount of RNLS was found in the renal tissues of clear cell renal cell carcinoma FG1; the amount of RNLS increased as the FG grades increased. Because RNLS increased significantly in renal tissues due to cancer, except for clear cell renal cell carcinoma FG1, RNLS may be useful biomarker for distinguishing grades of renal cancer. Because RNLS increases cell survival, anti-RNLS preparations may be useful for treating cancer in the future.

Onat, Taylan; Demir Caltekin, Melike; Doğanyigit, Züleyha; Turkler, Can; Kaymak, Emin; Kara, Mustafa; Serdar Yalvac, Ethem

We investigated the efficacy of activated cannabinoid 2 receptors for alleviating ovarian ischemia-reperfusion injury in rats. Female Wistar albino rats were divided randomly into six groups: ischemia-reperfusion (IRG); ischemia-reperfusion + 0.2 mg/kg JWH-133 (JIRG1), ischemia-reperfusion + 1 mg/kg JWH-133 (JIRG2); ischemia-reperfusion + 5 mg/kg JWH-133 (JIRG3); solvent control, and sham control. Ovarian ischemia was established for 3 h followed by reperfusion for 3 h. Ovarian tissue was investigated using histology, immunohistochemistry and biochemistry. Administration of JWH-133 synthetic cannabinoid reduced nuclear factor kappa-B immunoreactivity as well as TUNEL positivity scores and malondialdehyde levels. These reductions were significant in all cases except for the malondialdehyde levels in the 1 mg/kg JWH-133 group. Activation of cannabinoid 2 receptors by JWH-133 reduced ovarian ischemia-reperfusion injury due to its antioxidant and anti-inflammatory effects.