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Öğe A Phosphodiesterase Type-5 (PDE-5) Inhibitor, Sildenafil, Ameliorates the NEC Induced Inflammation(Springer, 2025) Ovali, Mehmet Akif; Oztopuz, Ozlem; Karaboga, IhsanThe connection between intestine microbiota and lung disease is described as the gut-lung axis, these organ systems are somehow interrelated in both homeostasis and disease development. In newborns, the most important gastrointestinal complications are necrotizing enterocolitis (NEC), and the pulmonary complication both cause significant systemic morbidity. In this study, sildenafil administered at varying doses in neonatal rat model of experimental necrotizing enterocolitis and focused on both mRNA expression and histopathological alterations. 15-day-old Wistar Albino rat pups were randomly divided into six groups; Control, NEC, DMSO, Sil_1mg, Sil_5mg, Sil_10mg (n = 5). NEC induction was performed using hypoxia/asphyxia and cold stress. At the end of the experiment, lung tissues were harvested, molecular and histopathological alterations were analysed. Histopathological examination was performed with hematoxylin&eosin and masson trichrome staining in lung samples of neonatal rats and the mRNA expression levels of TNF-alpha, IL-6 and HSPa5 genes were analyzed. The mRNA expression levels of TNF-alpha, IL-6 and HSPa5 were increased in the NEC group compared to the control group and sildenafil treatment could significantly reduced the levels of the genes and inflammation (*p < 0.05 and **p <= 0.0001). Alveolar edema and hemorrhage findings were observed in the lung tissue of the NEC group. Interstitial edema and hemorrhage findings were reduced in the groups treated with sildenafil compared to the NEC group. The data we obtained indicate that sildenafil administering at different doses has therapeutic effect on NEC induced lung tissue inflammation both at the mRNA expression and tissue levels.Öğe Humic Acid Has Protective Effect on Gastric Ulcer by Alleviating Inflammation in Rats(Pleiades Publishing Inc, 2022) Sehitoglu, Muserref Hilal; Oztopuz, Ozlem; Karaboga, Ihsan; Ovali, Mehmet Akif; Uzun, MetehanThe new agents are needed in treatment of gastric ulcer that have less side effects, adequate efficacy, and no drug interactions. In this study, we aimed to investigate the potential protective effects of humic acid on experimental gastric ulcer. Wistar Albino male rats (n = 48) were randomly divided into 8 groups as follow; Control (without any applications), Humic acid (50 mg/kg), ethanol group (1 mL/rat), and indomethacin group (25 mg/kg). In the treatment groups, both gastric ulcer model and humic acid 50 mg/kg were applied. In addition, famotidine the antiulcer drug was used as positive control. All medications were administered by oral gavage. Levels of ADAM10 and ADAMTS12 in gastric mucosa were determined by ELISA method. Hematoxylin-Eosin (H&E) staining, iNOS, and PCNA immunohistochemical staining were performed for histopathological investigations. Apoptosis was demonstrated by using the TUNEL method. In addition, the levels of inflammatory cytokines (TNF-alpha, IL-6, IL-10) and caspase-3 gene were determined by qRT-PCR. ADAM10 and ADAMTS12 levels significantly increased in the treatment groups compared to the ulcer groups (p < 0.05). The experimental groups showed mucosal erosion, bleeding, leukocyte infiltration and edema. Treatment with humic acid and famotidine was found to suppress iNOS activity, thereby decreasing proinflammatory activity and preventing damage to the gastric mucosa, while reducing the number of apoptotic cells. IL-6, IL-10, TNF-alpha and caspase-3 levels were significantly decreased in the treatment groups compared to damaged gastric mucosa. As a result, humic acid may be defined as a potential protective agent with its anti-inflammatory effect in gastric ulcer.Öğe Ozone treatment for high-dose systemic Steroid-Induced retinal injury(Taylor & Francis Ltd, 2020) Yildiz, Aydin; Sehitoglu, Muserref Hilal; Karaboga, Ihsan; Arikan, SedatObjective To investigate the effect of high-dose systemic steroids on retinal tissues and the effectiveness of ozone (O-3) therapy. Methods Twenty-four New Zealand white rabbits were divided into three groups of eight. Group 1 was accepted as the control group, Group 2 received intramuscular 20 mg/kg methylprednisolone acetate and Group 3 received 14 sessions of ozone treatment in addition to methylprednisolone acetate. The subjects were sacrificed on the 30(th)day. Retinal tissues were removed. Superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), total antioxidant status (TAS) and total oxidant status (TOS) levels were evaluated for tissue biochemistry and serum ischaemic modified albumin (IMA), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) levels were evaluated with the ELISA method. Haematoxylin-eosin staining and TUNEL evaluation for apoptosis were evaluated as histopathological methods. Results In the treatment group, antioxidant parameters of TAS, SOD and CAT were higher, oxidative and ischaemic parameters of MDA, TOS and IMA were lower, inflammatory parameters of IL-6 and TNF-alpha were lower, retinal thickness was better and apoptosis amount was lower. Conclusion Apoptosis increases in retinal tissues due to high dose systemic steroid administration and the retina becomes thinner. With biochemical examination, oxidation parameters increased while antioxidant parameters decreased. Both histopathological and biochemical parameters improved significantly with ozone treatment.Öğe Protective effect of gel form of gastric gavage applicated aloe vera on ischemia reperfusion injury in renal and lung tissue(C M B Assoc, 2017) Sahin, Hasan; Yener, Ali Umit; Karaboga, Ihsan; Sehitoglu, Muserref Hilal; Dogu, Tugba; Altinisik, Hatice Betul; Altinisik, UgurThe aloe vera plant has become increasingly popular in recent years. This study aimed to research the effect of aloe vera to prevent renal and lung tissue damage in an experimental ischemia-reperfusion (I/R) injury model. The study included 21 male Wistar Albino rats, which were categorized into control group, n = 7 (no procedures), Sham group n = 7 (I/R); and aloe vera therapy group, n = 7 (aloe vera and I/R). Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and malondialdehyde (MDA) were evaluated from lung and kidney tissues for biochemical investigations. As histopathological, hematoxylin and eosin and anti-iNOS were also examined. In biochemical investigations, SOD, CAT, and GPx levels of the Sham group were found to be lower compared with the other groups (P < 0.05). The aloe vera therapy group was not statistically different from control groups but significantly different compared with the Sham group. In the same way, the MDA levels of kidney and lung tissues were statistically significant in the aloe vera therapy group, compared to the Sham group. In the Sham group, the peribronchial and perialveolar edema were observed in lung parenchyma. Also, excess interstitial hemorrhage, leukocyte infiltration, and alveolar wall thickening were identified in ischemic groups. The histopathological changes were much lighter than in the aloe vera therapy group. In renal tissues, excess epithelial cell deterioration, tubular desqumination, and glomerular atrophy were observed in the Sham group. The histopathological changes were markedly reduced in the aloe vera therapy group. In the kidney and lung tissue, the level of iNOS activity in the Sham group was significantly higher than in the control and aloe vera therapy group. This study indicated that aloe vera is protective against oxidative damage formed by I/R in distant organs like the lungs and kidneys.Öğe Protective Effect of Hesperetin and Naringenin against Apoptosis in Ischemia/Reperfusion-Induced Retinal Injury in Rats(Hindawi Ltd, 2014) Kara, Selcuk; Gencer, Baran; Karaca, Turan; Tufan, Hasan Ali; Arikan, Sedat; Ersan, Ismail; Karaboga, IhsanPurpose. Hesperetin and naringenin are naturally common flavonoids reported to have antioxidative effects. This study was performed to investigate whether either hesperetin or naringenin has a protective effect against apoptosis on retinal ischemia/reperfusion (I/R) injury. Methods. Retinal I/R was induced by increasing the intraocular pressure to 150 mm Hg for 60 minutes. Thirty-three male Wistar albino rats were randomised into 5 groups named control, I/R + sham, I/R + solvent (DMSO), I/R + hesperetin, and I/R + naringenin. Animals were given either hesperetin, naringenin, or the solvent intraperitoneally immediately following reperfusion. Thickness of retinal layers and retinal cell apoptosis were detected by histological analysis, tunel assay, and immunohistochemistry assay. Results. Hesperetin and naringenin attenuated the I/R-induced apoptosis of retinal cells in the inner and outer nuclear cells of the rat retina. Retinal layer thickness of the naringenin treatment group was significantly thicker than that of the hesperetin, sham, and solvent groups (P < 0.05). Conclusions. Hesperetin and naringenin can prevent harmful effects induced by I/R injury in the rat retina by inhibiting apoptosis of retinal cells, which suggests that those flavanones have a therapeutic potential for the protection of ocular ischemic diseases.Öğe Quercetin protects the retina by reducing apoptosis due to ischemia-reperfusion injury in a rat model(Consel Brasil Oftalmologia, 2015) Arikan, Sedat; Ersan, Ismail; Karaca, Turan; Kara, Selcuk; Gencer, Baran; Karaboga, Ihsan; Tufan, Hasan AliPurpose: This study aimed to investigate the effect of quercetin on apoptotic cell death induced by ischemia-reperfusion (I/R) injury in the rat retina. Methods: Twenty-four rats were divided into four equal groups: control, ischemic, solvent, and quercetin. I/R injury was achieved by elevating the intraocular pressure above the perfusion pressure. Intraperitoneal injections of 20 mg/kg of quercetin and dimethyl sulfoxide (DMSO) were performed in the quercetin and solvent groups, respectively, immediately prior to I/R injury, and the researchers allowed for the retinas to be reperfused. Forty-eight hours after injury, the thicknesses of the retinal ganglion cell layer (RGCL), inner nuclear layer (INL), inner plexiform layer (IPL), outer plexiform layer (OPL), and outer nuclear layer (ONL) were measured in all groups. Moreover, the numbers of terminal deoxynucleotidyl transferase dUTP nick-end-labeled [TUNEL (+)] cells and caspase-3 (+) cells in both INL and ONL were evaluated in all groups. Results: The administration of quercetin was found to reduce the thinning of all retinal layers. The mean thickness of INL in the quercetin and ischemic groups was 21 +/- 5.6 mu m and 16 +/- 6.4 mu m, respectively (P<0.05). Similarly, the mean thickness of ONL in the quercetin and ischemic groups was 50 +/- 12.8 mu m and 40 +/- 8.7 mu m, respectively (P<0.05). The antiapoptotic effect of quercetin in terms of reducing the numbers of both TUNEL (+) cells and caspase-3 (+) cells was significant in INL. The mean number of TUNEL (+) cells in INL in the ischemic and quercetin groups was 476.8 +/- 45.6/mm(2) and 238.72 +/- 251/mm(2), respectively (P<0.005). The mean number of caspase-3 (+) cells in INL of ischemic and quercetin groups was 633.6 +/- 38.7/mm(2) and 342.4 +/- 36.1/mm(2), respectively (P<0.001). Conclusion: The use of quercetin may be beneficial in the treatment of retinal I/R injury because of its antiapoptotic effect on the retinal layers, particularly in INL.Öğe Royal jelly attenuates gastric mucosal injury in a rat ethanol-induced gastric injury model(Springer, 2020) Duran, Yasin; Karaboga, Ihsan; Polat, Fatin Rustu; Polat, Elif; Erboga, Zeynep Fidanol; Ovali, Mehmet Akif; Oztopuz, Rahime OzlemThe 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-kappa beta) 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 beta) and tumor necrosis factor-alpha (TNF-alpha) genes in gastric tissues was determined by real-time PCR; and TNF-alpha, IL-10, and IL-1 beta levels were determined. RJ was found to inhibit iNOS and Nf-kappa beta activity in the gastric mucosa and prevent epithelial cell apoptosis. In particular, pro-inflammatory cytokines TNF-alpha and IL-1 beta 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.Öğe Royal jelly attenuates gastric mucosal injury in a rat ethanol-induced gastric injury model (vol 47, pg 8867, 2020)(Springer, 2024) Duran, Yasin; Karaboga, Ihsan; Polat, Fatin Rustu; Polat, Elif; Erboga, Zeynep Fidanol; Ovali, Mehmet Akif; Oztopuz, Rahime Ozlem[Anstract Not Available]Öğe The hepatoprotective effect of Aloe vera on ischemia-reperfusion injury in rats(Kare Publ, 2019) Sehitoglu, Muserref Hilal; Karaboga, Ihsan; Kiraz, Asli; Kiraz, Hasan AliOBJECTIVE: Aloe vera is known for its antioxidant properties. In this experimental study, we aimed to investigate the efficacy of Aloe vera in ischemia-reperfusion (I/R) liver injury in rats. METHODS: Male Wistar Albino rats were divided into three groups, where the sham group (n=7) underwent no medication or surgical procedures, the I/R group (n=7) was the control group that received 45 minutes of applied abdominal aorta ischemia and rats were sacrificed 24 hours after reperfusion, and the I/R+AV group (n=7) was the treatment group that was given Aloe vera (30 mg/kg) every day followed by gastric lavage for a month before applying ischemia and performing sacrifice as in the previous group. Before sacrifice, all the liver tissues were removed. Tissues were examined for histopathological investigation, iNOS immunoreactivity and tissue biochemistry, malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) activities. RESULTS: The SOD, CAT, and GSH-Px levels of the I/R+AV group were not significantly different from the sham group (p>0.05) but were significantly higher when compared to the I/R group. MDA levels of liver tissues were significantly lower (p<0.05) in the I/R+AV group as compared to the I/R group. Disrupted hepatic cords, sinusoidal dilatation, hemorrhage, cytoplasmic vacuolization of hepatocytes, and intensive iNOS immunoreactivity were detected in the I/R group. Decreased histopathological change score and iNOS immunoreactivity score were noticed in the I/R+AV group as compared to the I/R group. CONCLUSION: It was found that Aloe vera showed a hepatoprotective effect against I/R injury. Further research is required to determine the effective dose, administration method, and effects of Aloe vera for liver transplantation.Öğe The protective effects of dexmedetomidine against apoptosis in retinal ischemia/reperfusion injury in rats(Taylor & Francis Ltd, 2014) Gencer, Baran; Karaca, Turan; Tufan, Hasan Ali; Kara, Selcuk; Arikan, Sedat; Toman, Huseyin; Karaboga, IhsanObjective: Dexmedetomidine is an alpha 2 adrenoceptor agonist and can be used for postoperative sedation, analgesia and anesthesia-sparing properties. Furthermore, the neuroprotective effects against ischemia/reperfusion (I/R) injury in the central nervous system have been shown in experimental studies. This study aimed to investigate the protective effects of dexmedetomidine against apoptosis in retinal I/R injury in the rat. Materials and methods: Retinal I/R injury was induced by transient elevation of intraocular pressure. Eighteen animals were divided into three groups (n = 6): sham, I/R and treatment. The I/R injury and protective effects of the dexmedetomidine were evaluated by retinal thickness determined by histological sections, terminal deoxynucleotidyl transferase-mediated biotin-deoxyuridine triphosphate nick-end labeling (TUNEL) and immunohistochemistry of caspases 3. Results: A decrease in the retinal thickness and an increase in the apoptotic cells were found to be statistically significant in I/R and treatment groups when compared with the control group. However, in comparison with the I/R group we realized that the administration of dexmedetomidine reduced the thinning of retinal thickness and also decreased the number of caspases 3 and TUNEL-positive cells. Conclusion: Dexmedetomidine is protective against apoptosis in retinal I/R injury in rats.
