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Öğe Anti-Apoptotic and Anti-Oxidant Effects of Caffeic Acid Phenethyl Ester on Cadmium-Induced Testicular Toxicity in Rats(Humana Press Inc, 2016) Erboğa, Mustafa; Kanter, Mehmet; Aktaş, Cevat; Dönmez, Yeliz Bozdemir; Erboğa, Zeynep Fidanol; Aktaş, Emel; Gürel, AhmetCadmium (Cd) is a serious environmental and occupational contaminant and may represent a serious health hazard to humans and other animals. Cd is reported to induce the generation of reactive oxygen species, and induces testicular damage in many species of animals. The goal of our study was to examine the anti-apoptotic and anti-oxidant effects of caffeic acid phenethyl ester (CAPE) on Cd-induced oxidative stress, apoptosis, and testicular injury in rats. A total of 40 male Wistar albino rats were divided into four groups: control, CAPE alone, Cd-treated, and Cd-treated with CAPE; each group consisted of 10 animals. To induce toxicity, Cd (1 mg/kg body weight) was dissolved in normal saline and subcutaneously injected into rats for 30 days. The rats in CAPE-treated group were given a daily dose of 10 mu mol/kg body weight of CAPE by using intraperitoneal injection. This application was continued daily for a total of 30 days. To date, no examinations of the anti-apoptotic and anti-oxidant properties of CAPE on Cd-induced apoptosis, oxidative damage, and testicular injury in rat testes have been reported. CAPE-treated animals showed an improved histological appearance and serum testosterone levels in Cd-treated group. Our data indicate a significant reduction in the number of apoptotic cells in testis tissues of the Cd-treated group with CAPE treatment. Moreover, CAPE significantly suppressed lipid peroxidation, compensated deficits in the anti-oxidant defenses in testes tissue resulted from Cd administration. These findings suggest that the protective potential of CAPE in Cd toxicity might be due to its anti-oxidant and anti-apoptotic properties, which could be useful for achieving optimum effects in Cd-induced testicular injury.Öğe Effect of hesperetin on inflammatory and oxidative status in trinitrobenzene sulfonic acid-induced experimental colitis model(Cellular and Molecular Biology Association, 2018) Polat, Fatin Rüştü; Karaboğa, İhsan; Polat, Muhammed Semih; Erboğa, Zeynep Fidanol; Yılmaz, Ahsen; Güzel, SavaşIn our study, the effect of hesperetin on inflammatory and oxidative status in trinitrobenzene sulfonic acid (TNBS)-induced experimental colitis model was investigated through different methods. Eighteen Wistar albino male rats were divided in to three groups: Group I (Control, n = 8; 1 ml physiological saline), Group II (Colitis, n = 8; 1 ml TNBS), Group III (Hesperetin, n = 8; 1 ml TNBS and 100 mg/kg hesperetin). Macroscopic and microscopic scores were calculated to determine the damage to the colon at the end of the experiment. Serum tumor necrosis factor-? (TNF-?) and tissue interleukin-6 (IL-6) levels were determined using the ELISA method. Myeloperoxidase (MPO), superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) levels were investigated spectrophotometrically. The TUNEL method was used for the detection of apoptotic cells in the colon tissue. Inducible nitric oxide synthase (iNOS) and nuclear factor-kappa-B (NF-??) expression in the colon were determined immunohistochemically. Hesperetin administration has shown to significantly reduce levels of MPO, MDA, and proinflammatory agents (TNF-?, IL-6, and NF-??). It has also been proven to inhibit mucosal apoptosis. This study indicates that hesperetin is protective against TNBS-induced colitis model via antiinflammatory, antioxidant and antiapoptotic effects. © 2018 by the C.M.B. Association. All rights reserved.Öğe Effect of Urtica Dioica against Doxorubicin-Induced Cardiotoxicity in Rats through Suppression of Histological Damage, Oxidative Stress and Lipid Peroxidation(Modestum Ltd, 2016) Erboğa, Mustafa; Dönmez, Yeliz Bozdemir; Şener, Ümit; Erboğa, Zeynep Fidanol; Aktaş, Cevat; Kanter, MehmetObjective: Doxorubicin (DOX) is a highly effective anti-cancer drug with limited clinical use due to its serious cardiotoxicity. Urtica dioica L. seeds (UD), have been widely used in folk medicine, particularly in the therapy for advanced cancer patients, possesses a potent anti-oxidant properties. The goal of present study was to investigate the cardioprotective effects of UD on DOX-induced cardiotoxicity. Method: The rats in the UD treated group were given intraperitoneally 2 ml/kg UD. To induce cardiotoxicity, 30 mg/kg DOX was injected intraperitoneally by a single dose and the rats were sacrificed after 48 h. Results: The present study revealed for the first time a protective role of UD against DOX-induced cardiotoxicity. UD therapy significantly protected against DOX-induced myocardial damage which was characterized by conduction abnormalities, vacuolization, inflammatory cell infiltration, hemorrhages, and myofibrillar disarrangement. As indicators of oxidative stress, DOX caused significantly increase lipid peroxidation and reduction in activities of antioxidant enzymes; superoxide dismutase, glutathione peroxidase, and catalase. UD treatment significantly attenuated DOX-induced oxidative injury. Conclusion: The present study showed that UD might be a suitable cardioprotector against toxic effects of DOX.Öğe Nigella sativa attenuates bleomycin-induced pulmonary fibrosis in rats by inhibition of inflammation, fibrosis, and inducible nitric oxide synthase(Ondokuz Mayis Universitesi, 2015) Erboğa, Mustafa; Erboğa, Zeynep Fidanol; Dönmez, Yeliz Bozdemir; Aktaş, Cevat; Kanter, MehmetThe present study investigated the anti-oxidant, anti-inflammatory and anti-fibrotic potential of Nigella sativa (NS) against bleomycin (BLC)-induced lung injury and fibrosis, an experimental animal model. A total of 18 male Sprague-Dawley rats were divided into three groups: Control, BLC, BLC+NS; each group consist of 6 animals. Pulmonary fibrosis was induced by a single intratracheal instillation of 2.5 mg/kg BLC. BLC+NS group rats were intragastric administered daily 400 mg/kg of NS from day 1 to 28. At the end of the study, lung tissues were removed for histopathological and immunohistochemical investigation. Lung tissues were stained with hematoxylin and eosin and Masson's Trichrome for histological evaluation. Moreover, the inducible nitric oxide synthase (iNOS) expression in the lung tissues was determined by immunohistochemical staining. BLC-induced histological changes including lung inflammation and lung fibrosis were significantly detected compared to the control group. NS treatment significantly ameliorated the BLC mediated histological changes and reduced the inflammatory cell infiltrate in lung tissues. NS significantly blocked collagen accumulations with parallel reduction in the fibrosis score. In addition, NS also markedly decreased the positive staining of iNOS in lung tissues. Our study provides evidence that NS significantly ameliorated BLM-induced pulmonary fibrosis in rats via the inhibition of inflammation score, fibrosis score, and iNOS expression. Therefore, NS may be a potential therapeutic reagent for the treatment of lung fibrosis. © 2015 OMU.Öğe Protective Effect of Nigella Sativa on Renal Reperfusion Injury in Rat(Iranian Soc Nephrolgy, 2016) Caskurlu, Turhan; Kanter, Mehmet; Erboğa, Mustafa; Erboğa, Zeynep Fidanol; Özgül, Mustafa; Atis, GokhanIntroduction. This study was designed to investigate the effect of Nigella sativa (NS), in reperfusion-induced renal injury in rats. Materials and Methods. A total of 24 male Sprague-Dawley rats were divided into 3 groups of controls and rats that underwent ischemia-reperfusion with and without pretreatment with NS. A rat model of renal reperfusion injury was induced by 45-minute occlusion of the bilateral renal pedicles and 24-hour reperfusion. In the NS group, a single dose NS (400 mg/kg orally) was administered by gastric gavage. Results. Renal reperfusion caused severe histopathological injury such as tubular damage, atrophy dilatation, loss of brush border, and hydropic epithelial cell degenerations. Treatment with NS significantly attenuated the severity of reperfusion injury and significantly lowered tubulointerstitial damage score as compared with the reperfusion group. When kidney sections were stained with anti-proliferating-cell nuclear antigen antibody, nuclear factor kappaB p65 antibody, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, there was a clear increase in the number of positive cells in the reperfusion group in the renal cortical tissues. However, there was a significant reduction in the number of stain-positive cells in kidney tissue from the NS group. Treatment of renal reperfusion injury with NS decreased the elevated tissue malondialdehyde levels and increased the reduced activities of the enzymatic antioxidants glutathione peroxidase and catalase. Conclusions. Pretreatment with NS has a protective effect against renal damage induced by renal reperfusion. This protective effect is possibly due to its ability to inhibit reperfusion-induced renal damage, apoptosis, and cell proliferation.Öğe Protective effects of hesperetin on lipopolysaccharide-induced acute lung injury in a rat model(Baycinar Medical Publishing, 2020) Kaya, S.; Kaya, S.A.; Polat, E.; Erboğa, Zeynep Fidanol; Duran, Y.; Polat, Fatin Rüştü; Karaboğa, İhsanBackground: In this experimental study, we aimed to investigate the effects of hesperetin, a natural flavonoid, on a lipopolysaccharideinduced acute lung injury model in rats. Methods: Between March 2019 and May 2019, a total of 18 adult male Wistar albino rats, weighing approximately 250 to 300 g, were randomly divided into three groups as control, lipopolysaccharide, and lipopolysaccharide + hesperetin groups (n=6 in each group). The wet/dry weight ratio of lung tissue was determined. Histopathological changes were examined using light and scanning electron microscopy. Pulmonary nuclear factor-kappa beta, inducible nitric oxide synthase, and alpha-smooth muscle antigen activity were determined with indirect immunohistochemical methods. Pulmonary apoptosis was detected with the terminal deoxynucleotidyl transferase dUTP nick-end labeling method. Tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, and interleukin-10 concentrations were measured with enzyme-linked immunosorbent assay. Results: Treatment with hesperetin significantly improved the architecture of lung tissue and reduced the wet/dry weight ratio, nuclear factor-kappa beta, inducible nitric oxide synthase, and alphasmooth muscle antigen expression, pulmonary apoptosis, and levels of proinflammatory cytokines. Conclusion: Our study results suggest that hesperetin has a potent protective effect against lipopolysaccharide-induced acute lung injury in rats via suppression of the proinflammatory cytokine cascade, nuclear factor-kappa beta, signaling pathway activation, and apoptosis. © 2020 All right reserved by the Turkish Society of Cardiovascular Surgery.Öğe Quercetin ameliorates methotrexate-induced renal damage, apoptosis and oxidative stress in rats(Taylor & Francis Ltd, 2015) Erboğa, Mustafa; Aktaş, Cevat; Erboğa, Zeynep Fidanol; Dönmez, Yeliz Bozdemir; Gürel, AhmetBackground: In the present study, the protective and therapeutic effects of quercetin (QE) on renal injury induced by methotrexate (MTX) have been examined. Materials and methods: A total of 24 male rats were divided into the following three groups: control group, MTX group, and MTX+QE group. Rats in MTX group received 20mg/kg of single dose of MTX, while those in MTX+QE group received 20mg/kg of single dose MTX, in addition to 15mg/kg of QE administered 30min prior to MTX and in the following 5-day period as a single daily dose. At the end of the experimental period, renal tissues were removed for histopathological and biochemical assessments. Results: Light microscopic examination showed a disruption of the renal structure in rats in MTX group in the form of tubular degeneration and dilation, with shedding of the tubular epithelial cells into the lumen. QE treatment was associated with less marked degenerative changes, with a similar histological appearance to that of controls. Furthermore, QE treatment resulted in decreased the number of apoptotic cells. Biochemical assessments showed significantly higher malondialdehyde (MDA) levels in MTX group as compared to control and MTX+QE groups. superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) levels showed a significant decrease in MTX group as compared to controls. However, QE significantly suppressed MDA level, compensated deficits in the anti-oxidant defenses [reduced SOD, GSH-Px, and CAT levels] in kidney tissue resulted from MTX administration. Conclusions: In conclusion, renal toxic effects of MTX may be alleviated by QE.Öğe Royal jelly attenuates gastric mucosal injury in a rat ethanol-induced gastric injury model(Springer Science and Business Media B.V., 2020) Duran, Y.; Karaboğa, İhsan; Polat, Fatin Rüştü; Polat, E.; Erboğa, Zeynep Fidanol; Ovalı, M. A.; Yılmaz, A.; Çelikkol, A.The aim of the study was to investigate traditionally used Royal Jelly (RJ) for treating an ethanol-induced gastric ulcer model in rats. A total of 32 Wistar albino male rats were divided into 4 groups of 8: group I = Control, group II = Ethanol, group III = RJ + Ethanol, and group IV = Lansoprazole + Ethanol. In groups II, III, and IV, animals were administered 1 ml of absolute ethanol orally after a 24-h fast to induce ulcer formation. The histopathological changes in the gastric mucosa were determined using hematoxylin-eosin (H&E) staining. Immunohistochemically, inducible nitric oxide (iNOS) and nuclear factor kappa beta (Nf-??) markings were evaluated in gastric tissue. Cell death in the gastric mucosa was determined by the TUNEL method. Oxidative status markers, superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), and myeloperoxidase (MPO) levels were determined spectrophotometrically. Expression of the interleukin – 1 beta (IL-1?) and tumor necrosis factor-? (TNF-?) genes in gastric tissues was determined by real-time PCR; and TNF-?, IL-10, and IL-1? levels were determined. RJ was found to inhibit iNOS and Nf-?? activity in the gastric mucosa and prevent epithelial cell apoptosis. In particular, pro-inflammatory cytokines TNF-? and IL-1? levels were significantly decreased in the RJ + Ethanol group compared to the Ethanol group. In addition, a decrease in the MPO level indicated that RJ prevented tissue damage, especially by preventing inflammatory cell infiltration. The study demonstrated a possible gastroprotective effect of RJ in a rat ethanol-induced gastric ulcer model. © 2020, Springer Nature B.V.Öğe Thymoquinone Ameliorates Cadmium-Induced Nephrotoxicity, Apoptosis, and Oxidative Stress in Rats is Based on its Anti-Apoptotic and Anti-Oxidant Properties(Humana Press Inc, 2016) Erboğa, Mustafa; Kanter, Mehmet; Aktaş, Cevat; Şener, Ümit; Erboğa, Zeynep Fidanol; Dönmez, Yeliz Bozdemir; Gürel, AhmetCadmium (Cd), an environmental and industrial pollutant, generates free radicals responsible for oxidative stress. Cd can also lead to various renal toxic damage such as the proximal tubules and glomerulus dysfunction. Thymoquinone (TQ) is the main constituent of the essential oil obtained from black seeds (Nigella sativa) and has various pharmacological effects. The aim of the present study was to examine the nephroprotective, anti-oxidant, and anti-apoptotic effect of the TQ against Cd-induced nephrotoxicity. A total of 24 male Wistar albino rats were divided into three groups: control, Cd-treated, and Cd-treated with TQ; each group contain eight animals. The Cd-treated group was injected subcutaneously with CdCl2 dissolved in saline in the amount of 2 ml/kg/day for 30 days, resulting in a dosage of 1 mg/kg Cd. The rats in TQ-treated groups were given TQ (50 mg/kg body weight) once a day orally together with first Cd injection during the study period. The histopathological studies in the kidney of rats also showed that TQ markedly reduced the toxicity of Cd and preserved the normal histological architecture of the renal tissue. Immunohistochemical analysis revealed that TQ significantly decreased the Cd-induced over expression of nuclear factor-kappa B in renal tissue. Furthermore, TQ treatment resulted in decreased the number of apoptotic cells. TQ significantly suppressed lipid peroxidation, compensated deficits in the anti-oxidant defenses (reduced superoxide dismutase, glutathione peroxidase and catalase activities) in renal tissue resulted from Cd administration. These findings suggest that the nephroprotective potential of TQ in Cd toxicity might be due to its anti-oxidant and anti-apoptotic properties, which could be useful for achieving optimum effects in Cd-induced nephrotoxicity.Öğe Toxicological assessment of low-dose bisphenol A, lead and endosulfan combination: chronic toxicity study in male rats(Springer Science and Business Media Deutschland GmbH, 2022) Dökmeci, Ayşe Handan; Karaboğa, İhsan; Güzel, S.; Erboğa, Zeynep Fidanol; Yılmaz, A.In the present study, toxic effects, both alone and combined, of bisphenol A (BPA), lead (Pb) and endosulfan (ES) in the low doses were investigated in rat liver and kidney functions. In the study, bisphenol A (BPA), lead (Pb) and endosulfan (ES) were chosen because although they are the chemicals people are most frequently exposed to, no combined toxic effect studies were conducted with these chemicals. Sixty-four male Wistar albino rats were used in the study, and they were randomly divided into eight groups (n = 8 per group); control, BPA (5 mg/kg), Pb (100 ppm), ES (0.61 mg/kg), BPA+Pb, BPA+ES, Pb+ES and BPA+P+ES. The rats were sacrificed after 65 days of treatment. Severe histopathological changes in the liver and kidney tissues were observed in the rats exposed to BPA+Pb+ES combination. Elevated malondialdehyde (MDA) in the liver and decreased superoxide dismutase activity (SOD) in the kidney tissue were detected in the BPA+Pb+ES group compared to those of the control group. It was found that serum alanine aminotransferase (ALT) and blood urea nitrogen (BUN) and creatinine (CREA) levels were higher in the BPA+Pb+ES combination group than the control group. Also, combined exposure of BPA, Pb and ES caused apoptotic cell numbers and inducible nitric oxide (iNOS) to increase in the liver and kidney tissues. The results of the present study suggested that the BPA, Pb and ES caused more dramatic changes to both histological architecture and cell apoptosis in the liver and kidney tissues when there was a combined exposure. © 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
