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Öğe Ascorbic acid mitigates doxorubicin-induced spleen injury in rats: Histopathological and immunohistochemical insights(Univ Karachi, 2024) Gezer, Arzu; Ozkaraca, Mustafa; Sari, Ebru Karadag; Bedir, Gursel; Aydin, Pelin; Asker, Hasan; Abd El-Aty, AmThis study assessed the protective potential of ascorbic acid against doxorubicin-induced spleen tissue damage in rats. Twenty-eight male Sprague-Dawley rats were divided into four groups. The control group received saline every other day at a dose of 1mL throughout the experiment. The ascorbic acid group was administered 50mg/kg of ascorbic acid daily for 10 days. The doxorubicin group received a single dose of 15mg/kg of doxorubicin on day 7. The ascorbic acid + doxorubicin group received both 50mg/kg of ascorbic acid daily for 10 days and a single dose of 15mg/kg of doxorubicin on day 7. After the experiment, splenic tissue samples were examined histopathologically and immunohistochemically. Histopathological analysis revealed edema, destruction, and degeneration in the doxorubicin group, but these changes were alleviated in the ascorbic acid-treated group, approaching control group levels. Immunohistochemical analysis showed increased CD4(+) and CD8(+) cell immunopositivity in the ascorbic acid + doxorubicin group compared to the doxorubicin group. Biochemical tests indicated that doxorubicin reduced superoxide dismutase activity and increased malondialdehyde levels, whereas ascorbic acid mitigated these effects. The findings suggest that ascorbic acid may have a protective role against doxorubicin-induced spleen injury in rats.Öğe Ascorbic acid mitigates doxorubicin-induced spleen injury in rats: Histopathological and immunohistochemical insights(Univ Karachi, 2024) Gezer, Arzu; Ozkaraca, Mustafa; Sari, Ebru Karadag; Bedir, Guersel; Aydin, Pelin; Asker, Hasan; Abd El-Aty, AmThis study assessed the protective potential of ascorbic acid against doxorubicin-induced spleen tissue damage in rats. Twenty-eight male Sprague-Dawley rats were divided into four groups. The control group received saline every other day at a dose of 1mL throughout the experiment. The ascorbic acid group was administered 50mg/kg of ascorbic acid daily for 10 days. The doxorubicin group received a single dose of 15mg/kg of doxorubicin on day 7. The ascorbic acid + doxorubicin group received both 50mg/kg of ascorbic acid daily for 10 days and a single dose of 15mg/kg of doxorubicin on day 7. After the experiment, splenic tissue samples were examined histopathologically and immunohistochemically. Histopathological analysis revealed edema, destruction, and degeneration in the doxorubicin group, but these changes were alleviated in the ascorbic acid -treated group, approaching control group levels. Immunohistochemical analysis showed increased CD4(+) and CD8(+) cell immunopositivity in the ascorbic acid + doxorubicin group compared to the doxorubicin group. Biochemical tests indicated that doxorubicin reduced superoxide dismutase activity and increased malondialdehyde levels, whereas ascorbic acid mitigated these effects. The findings suggest that ascorbic acid may have a protective role against doxorubicin-induced spleen injury in rats.Öğe Black Garlic Extract Modulates Endothelin Expression and Ovulatory Function in Monosodium Glutamate Treated Rats(Wiley, 2025) Gezer, Arzu; Aras, Sukran Yediel; Ozkaraca, Mustafa; Baygutalp, Nurcan Kilic; Gundogdu, Gulhande; Sari, Ebru Karadag; Bedir, GurselMonosodium glutamate (MSG), a widely used food additive, has been associated with various health concerns, including potential reproductive toxicity. This study investigated the protective effects of black garlic (BG) ethanol extract against MSG-induced ovarian damage in rats. Thirty-two female rats in estrus were randomly divided into four groups (n = 8 per group): control (saline), BG (250 mg/kg BW), MSG (4 mg/g BW), and BG+MSG (combined treatment). Treatments were administered daily for 14 days. Ovarian tissues were collected for histopathological, immunohistochemical (IHC), and biochemical analyses. Histopathological examination revealed a significant reduction in cystic follicles in the BG+MSG group compared to the MSG group (p < 0.0001). IHC analysis showed decreased immunoreactivity of endothelin-1 and endothelin-2 in the BG+MSG group compared to the MSG group (both p < 0.01). Biochemical assays demonstrated significantly increased follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol levels in the BG+MSG group compared to the MSG group (all p < 0.05), while progesterone levels were significantly lower in the MSG group compared to the BG+MSG group (p < 0.05). These findings suggest that BG ethanol extract may mitigate MSG-induced ovarian dysfunction in rats by alleviating degenerative changes in follicles and modulating hormonal levels. This study provides insights into potential natural interventions for MSG-related reproductive toxicity.Öğe Cilomilast, a PDE4 Inhibitor, Suppresses CD4++ and CD8++ T Cell Proliferation in the Thymus and Spleen of Rats: Mechanism of Glutathione Reduction(Univ Agriculture, Fac Veterinary Science, 2024) Gezer, Arzu; Baygutalp, Nurcan Kilic; Cengiz, Mustafa; Gur, Bahri; Ozkaraca, MustafaCilomilast is an oral phosphodiesterase-4 (PDE4) inhibitor recommended for treating COPD. However, its side effects and low therapeutic index remain an unresolved problem in clinical practice. This study aimed to evaluate the effects of cilomilast on the spleen and thymus tissues of rats. For experimental studies, 24 male Sprague-Dawley rats weighing 200-220g were randomly divided into three experimental groups: The procedures were repeated for 7 days for the control, sham, and cilomilast groups. Blood and tissue samples were collected from the rats under anesthesia on day 8 of the experiment for analysis. p<0.05 at a 95% confidence level was considered to indicate statistical significance. Severe tissue damage in the thymus and spleen was observed in the cilomilast group. In the thymus and spleen tissues of the control and sham groups, CD4+ + and CD8+ + cell immunopositivity were more intense, while the density of these cells was significantly reduced in the cilomilast group. In addition, glutathione (GSH) levels decreased, and nitric oxide levels increased in both tissues of the cilomilast group. However, in-silico results showed that the decrease in GSH levels is due to the enzymes gamma-glutamylcysteine synthase and glutathione synthase, which act as catalysts in the two-step GSH biosynthesis mechanism. Suppression of the immune system targets both harmful and compensatory pathways so that both beneficial mechanisms and pathological changes can be blocked. To eliminate these cilomilast-induced side effects and enable more effective clinical application, it may be recommended to develop formulations such as lipid-based inhaled forms or nano-drug delivery systems including dendrimers, reverse micelle systems, polymeric or lipid-based carriers as an alternative to conventional application.Öğe Docosahexaenoic acid eliminates endoplasmic reticulum stress and inflammatory pathways in diabetic rat keratopathy(Elsevier, 2024) Gezer, Arzu; Ozkaraca, Mustafa; Ustundag, Hilal; Soydan, Menekse; Alkanoglu, Omer; Bedir, GurselDiabetic keratopathy, characterized by corneal structural changes, is a common complication of diabetes mellitus (DM). Docosahexaenoic acid (DHA), an omega-3 fatty acid, has shown potential therapeutic benefits in various diabetic complications. This study aimed to investigate the protective effect of DHA on corneal tissue in streptozotocin (STZ)-induced type 2 DM in rats. Forty male Sprague-Dawley rats were randomly assigned to four groups (n = 10 per group): Control, DHA, DM, and DM + DHA. The DHA group received DHA by oral gavage at a dose of 100 mg/kg daily for 10 days. In the DM group, diabetes was induced by a single intraperitoneal injection of STZ at 50 mg/kg. Confirmation of diabetes induction was based on monitoring fasting blood glucose levels on the third day post-injection. The DM + DHA group underwent the same diabetes induction protocol with STZ and received DHA at 100 mg/kg daily via oral gavage for 10 consecutive days. Corneal tissue samples were collected at the end of the study period for histopathological, immunohistochemical, qRT-PCR, and ELISA analyses. Histopathological analysis showed significant edema, angiogenesis, and degeneration in the DM group compared to the control (p < 0.001). DHA treatment significantly mitigated these changes, approaching control levels (p < 0.01). Immunohistochemistry showed increased VEGFR2 and iNOS expression in the DM group, which was significantly reduced in the DM + DHA group (p < 0.01). qRT-PCR results indicated a significant decrease in Bcl-2 expression (p < 0.001) and an increase in ATF-6, IRE1, NF-kappa B, TNF-alpha, IL-1 beta, NLRP3, Bax, and Caspase-3 expressions in the DM group (p < 0.001). ELISA analyses revealed significantly elevated levels of inflammatory markers NF-kappa B, TNF-alpha, IL-1 beta, and IL-6 in the DM group compared to the control (p < 0.001). DHA treatment significantly upregulated Bcl-2 and downregulated apoptotic and inflammatory markers (p < 0.01). DHA demonstrated significant protective effects against STZ-induced corneal damage in diabetic rats by modulating apoptotic and inflammatory pathways. These findings suggest that DHA may be a promising therapeutic agent for preventing diabetic keratopathy.Öğe Effects of apixaban, rivaroxaban, dabigatran and enoxaparin on histopathology and laboratory parameters in Achilles tendon injury: An in vivo study(Wolters Kluwer Medknow Publications, 2021) Avci, Sema; Gungor, Huseyin; Kumru, Alper Serhat; Sahin, Mahmut; Gezer, Arzu; Gok, Uzeyir; Kara, HakiObjectives: To compare the effects of apixaban, rivaroxaban, dabigatran and enoxaparin on histopathology and blood parameters in rats with Achilles tendon injury. Materials and Methods: Thirty adult, male Wistar albino rats weighting 220-240 g were randomly divided into five (one control and four treatment) groups and placed in a controlled environment. The Achilles tendon was incised and re-sutured in each rat, after which each group was provided the following treatment for 28 days: a) 2 ml saline to the control group, b) apixaban in 1 ml of saline (10 mg/kg/day) +1 ml of saline, c) rivaroxaban in 1 ml of saline (2 mg/kg/day) +1 ml saline, d) dabigatran in 1 ml of saline (30 mg/kg/day) +1 ml of saline, e) enoxaparin (80 mu g/kg/day) + 2 ml of saline. Results: Hemogram, biochemical and coagulation parameters differed significantly between the control and treatment groups (P < 0.05). Compared with the control group, in the apixaban group, type I and type III collagen immunoreactivity were severe and moderate, respectively. In the rivaroxaban and dabigatran groups, both type I and type III collagen immunoreactivity were medium and severe, respectively. In the enoxaparin group, type I and type III collagen immunoreactivity were mild and severe, respectively. Conclusion: The higher concentration of type I collagen in the apixaban and dabigatran indicates faster tendon healing in these groups, and the higher concentration of the type III collagen in the enoxaparin group indicates slower healing in this group.Öğe Exploring the neuroprotective effects of black garlic ethanol extract on acrylamide-induced brain damage through apoptotic and neurodegenerative pathways(Ankara Univ, 2024) Gezer, Arzu; Karadag Sari, Ebru; Gelen, Volkan; Elis Yildiz, Sevda; Ozkaraca, Mustafa; Bedir, Gursel; Calik, FatmaThis research focused on exploring the therapeutic impact of black garlic ethanol extract (BGE) on the brain tissue of rats exposed to acrylamide (ACR). Twenty-four female rats were divided into four groups. Rats in the control group were given 1 ml of saline by oral gavage for 14 days. The BG group received 5 mg/200 g of BGE extract on a daily basis. The ACR group was administered 40 mg/kg of ACR daily. Rats in the BGE+ACR group received both 5 mg/200 g of BG extract and 40 mg/kg of ACR daily. Brain tissue samples were collected at the study's conclusion for histopathological, immunohistochemical, and biochemical analyses. Hematoxylin-eosin staining was performed to examine the general structure of the brain tissue. Erk1/2, pERK1/2, and c-fos were analyzed immunohistochemically; Bcl-2, Caspase-3, ATF6, CREB, and NfkB-p65 protein levels were analyzed by Western blotting; and MDA, SOD, CAT, GSH, TNF-alpha, IL-1(3, and IL-6 activities and levels were analyzed using ELISA kits. It was determined that ACR application raised the levels of Erk1/2, p-ERK1/2, c-Fos, NfkB-p65, caspase-3, MDA, IL-6, IL-1-(3, and TNF-alpha, and BGE supplementation decreased this increase. ACR exposure caused a decrease in Bcl-2, ATF6, CREB, CAT, GSH, and SOD expressions, and BGE supplementation prevented or increased this decrease. Based on the findings obtained, it can be said that the ethanol extract of black garlic has antioxidative and anti-inflammatory effects, prevents cell damage, and has positive effects on apoptosis in rat brain tissue.Öğe Sinapic acid reduces pentylenetetrazol induced seizures in rats(Natl Inst Science Communication-Niscair, 2024) Ekici, Mehmet; Guene, Handan; Gezer, ArzuSeizure is known to induce oxidative stress which may initiate neuronal death. Oxidant-antioxidant imbalance often leads to mitochondrial dysfunction, inflammation, and apoptosis in the brain which may further result in the development of seizure. Phenolic compounds such as curcumin and rosmarinic acid are reported to control convulsions and seizures in pentylenetetrazol induced seizures models by suppressing seizure time, oxidative stress and inflammation indirectly. Sinapic acid (SA), a polyphenolic product of hydroxycinnamic acid found in various plants, exhibits anti-inflammatory, antioxidant and anxiolytic effects. In this study, we investigated the effects of sinapic acid on pentylenetetrazol induced seizures in rats through oxidative stress, inflammation, apoptosis, and neurotrophic factor. A total of 28 male Wistar Albino rats weighing 200-220 g were divided into four equal groups (n=7/group). The treatment groups received 10 mg/kg and 20 mg/kg SA, respectively, by oral gavage for five consecutive days along with pentylenetetrazol (45 mg/kg, intraperitoneal) to induce seizures. The levels of Total oxidant status (TOS), Total antioxidant status (TAS), TNF-alpha, IL-113, and Brain-derived neurotrophic factor (BDNF) were measured in the cortex and hippocampus. Additionally, caspase 3 and caspase 9 levels, as well as the immunoreactivity of Cleaved caspase 3, were determined in the hippocampus. The results showed that pretreatment with 20 mg/kg SA delayed the latency of generalized tonic-clonic seizures (GTCS) and first myoclonic jerk, reduced GTCS duration, and improved seizure score and cognitive function. Importantly, the 20 mg/kg SA pretreatment resulted in decreased levels of TOS, TNF-alpha, IL-113, and BDNF in the cortex and hippocampus, while increasing TAS levels in these brain areas. Moreover, the 20 mg/kg SA reduced hippocampal caspase 3 and caspase 9 levels, as well as the immunoreactivity of Cleaved caspase 3 in rats with pentylenetetrazol-induced seizures. These findings suggest that the anti-seizure effects of SA are mediated by BDNF modulation, as well as its antioxidant, anti-inflammatory, and antiapoptotic properties.Öğe Sinapic acid reduces pentylenetetrazol induced seizures in rats(Council Of Scientific And Industrial Research (CSIR) National Institute Of Science Communication and Policy Research (NIScPR), 2024/05/31) Ekici, Mehmet; Güneş, Handan; Gezer, ArzuSeizure is known to induce oxidative stress which may initiate neuronal death. Oxidant-antioxidant imbalance often leads to mitochondrial dysfunction, inflammation, and apoptosis in the brain which may further result in the development of seizure. Phenolic compounds such as curcumin and rosmarinic acid are reported to control convulsions and seizures in pentylenetetrazol induced seizures models by suppressing seizure time, oxidative stress and inflammation indirectly. Sinapic acid (SA), a polyphenolic product of hydroxycinnamic acid found in various plants, exhibits anti-inflammatory, antioxidant and anxiolytic effects. In this study, we investigated the effects of sinapic acid on pentylenetetrazol induced seizures in rats through oxidative stress, inflammation, apoptosis, and neurotrophic factor. A total of 28 male Wistar Albino rats weighing 200-220 g were divided into four equal groups (n=7/group). The treatment groups received 10 mg/kg and 20 mg/kg SA,respectively, by oral gavage for five consecutive days along with pentylenetetrazol (45 mg/kg, intraperitoneal) to induceseizures. The levels of Total oxidant status (TOS), Total antioxidant status (TAS), TNF-α, IL-1β, and Brain-derivedneurotrophic factor (BDNF) were measured in the cortex and hippocampus. Additionally, caspase 3 and caspase 9 levels, aswell as the immunoreactivity of Cleaved caspase 3, were determined in the hippocampus. The results showed thatpretreatment with 20 mg/kg SA delayed the latency of generalized tonic-clonic seizures (GTCS) and first myoclonic jerk,reduced GTCS duration, and improved seizure score and cognitive function. Importantly, the 20 mg/kg SA pretreatmentresulted in decreased levels of TOS, TNF-α, IL-1β, and BDNF in the cortex and hippocampus, while increasing TAS levelsin these brain areas. Moreover, the 20 mg/kg SA reduced hippocampal caspase 3 and caspase 9 levels, as well as theimmunoreactivity of Cleaved caspase 3 in rats with pentylenetetrazol-induced seizures. These findings suggest that theanti-seizure effects of SA are mediated by BDNF modulation, as well as its antioxidant, anti-inflammatory, and anti-apoptotic properties.Öğe The effect of taxifolin on oxidative ovarian damage and reproductive dysfunctions induced by antipsychotic drugs in female rats(Wiley, 2021) Ince, Sefa; Ozer, Mehmet; Kadioglu, Berrin Goktug; Kuzucu, Mehmet; Ozkaraca, Mustafa; Gezer, Arzu; Suleyman, HalisAim Typical antipsychotics (TAPs) are commonly used to treat schizophrenia and bipolar disorder. However, extrapyramidal disorders, hyperprolactinemia, and reproductive dysfunctions have been observed in women during the use of TAPs. For this reason, less toxic and prolactin-sparing atypical antipsychotic (AAP) drugs such as clozapine (CLN) have been developed. The aim of this study is to investigate the effect of taxifolin on possible ovarian and reproductive toxicity associated with CLN and haloperidol (HPL) in female Wistar albino rats. Methods The rats were grouped as healthy control group (HCG), CLN, HPL, taxifolin + clozapine (TCL), and taxifolin + haloperidol (THL). Drugs were administered to the groups for 28 days. At the end of that time, ovarian tissues of six rats from each group were taken for histopathological and biochemical analyses. Remaining six rats in groups were examined for evaluation of reproductive dysfunctions. Results Severe degeneration and vacuolization were observed in the primary, secondary, and primordial follicles of the ovarian tissues of CLN- and HPL-treated groups, of which malondialdehyde (MDA) level was high and total glutathione (tGSH) level was low. In the taxifolin-treated groups, taxifolin significantly prevented the increase of MDA level and decrease of tGSH level, and the severity of histopathological damage was found to be lower. In addition, it was found that taxifolin significantly prevented infertility and delay in pregnancy associated with CLN and HPL. Conclusions The results of this experiment suggest that taxifolin can be beneficial in treating oxidative ovarian damage, infertility, and reproductive dysfunctions induced by CLN and HPL.Öğe The Protective Effect of Gallic Acid Against Bisphenol A-Induced Ovarian Toxicity and Endocrine Disruption in Female Rats(Mary Ann Liebert, Inc, 2024) Gezer, Arzu; Ustundag, Hilal; Baygutalp, Nurcan Kilic; Erbas, Elif; Ozkaraca, MustafaPurpose: This study aimed to investigate the protective effects of gallic acid (GA) against ovarian damage induced by bisphenol A (BPA) exposure in female rats. We evaluated whether GA can mitigate the adverse effects of BPA on ovarian structure, inflammatory markers, oxidative stress, apoptosis, and reproductive hormone levels. Methods: Thirty-two female rats were categorized into four groups: control, GA, BPA, and GA+BPA. Histopathological evaluations of ovarian tissue were performed using hematoxylin-eosin staining. The immunohistochemical analysis was conducted for inflammatory, oxidative DNA damage, and apoptotic markers (Tumor necrosis factor alpha [TNF alpha], cyclooxygenase-2 [COX2], interleukin-1 beta [IL-1 beta], 8-hydroxydeoxyguanosine [8-OHdG], and caspase 3). Oxidative stress was assessed by measuring malondialdehyde and superoxide dismutase levels. Furthermore, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estrogen, and progesterone levels were quantified using enzyme-linked immunosorbent assay. Results: Histopathological outcomes revealed that BPA significantly induced follicular degeneration, which was effectively mitigated by GA treatment (P < 0.05). Immunohistochemical analysis highlighted the exacerbation of inflammatory responses and oxidative DNA damage and apoptosis (TNF alpha, COX-2, IL-1 beta, 8-OHdG, and caspase 3) in BPA-exposed tissues, which were reduced in the presence of GA (P < 0.05). The assessment of oxidative stress demonstrated that GA could significantly decrease lipid peroxidation and partially restore antioxidant defense mechanisms disrupted by BPA (P < 0.05). Hormonal profiling indicated that BPA exposure altered the levels of FSH, LH, estrogen, and progesterone, with GA treatment showing a capacity to modulate these changes, especially in progesterone levels (P < 0.05). Conclusions: The findings suggest that GA exhibits protective properties against BPA-induced ovarian damage through its antioxidative and anti-inflammatory activities, alongside its ability to modulate hormonal imbalances. This research underscores the therapeutic potential of GA in safeguarding reproductive health against environmental toxicants.Öğe Therapeutic effects of resveratrol and β-carotene on L-arginine-induced acute pancreatitis through oxidative stress and inflammatory pathways in rats(Nature Portfolio, 2024) Gezer, Arzu; Ustundag, Hilal; Ozkaraca, Mustafa; Sari, Ebru Karadag; Gur, CihanAcute pancreatitis (AP) is a severe inflammatory condition affecting the pancreas, often leading to systemic inflammation and organ dysfunction. This study evaluated the effects of resveratrol (RES) and beta-carotene (beta C) on L-arginine-induced AP in rats. Forty-eight male Sprague Dawley rats were divided into six groups: Control (C), RES (20 mg/kg), beta C (50 mg/kg), AP, AP + RES, and AP + beta C. The AP model was induced with 250 mg/100 g L-arginine intraperitoneally twice daily with a 1-h interval. The AP group showed significantly elevated oxidative stress (MDA) and reduced GSH levels (p < 0.001). Immunohistochemical (IHC) staining with anti-insulin antibody revealed reduced beta + langerhans islet size in the AP group. qPCR analysis indicated significant upregulation of inflammatory genes NF-kappa B, TNF-alpha, and IL-1 beta (p < 0.001), and apoptotic genes Bax and Caspase-3, with downregulation of Bcl-2 (p < 0.001). RES and beta C treatments significantly reduced MDA levels and increased GSH levels (p < 0.01 for both) compared to the AP group. The AP + RES and AP + beta C groups exhibited preserved beta + Langerhans islet size (p < 0.01), suppressed NF-kappa B, TNF-alpha, and IL-1 beta expression, reduced Bax and Caspase-3 levels, and increased Bcl-2 levels (p < 0.01). Histopathological findings supported these results. RES and beta C confer significant effects against L-arginine-induced acute pancreatitis by reducing oxidative stress, preserving pancreatic islet integrity, suppressing inflammatory responses, and modulating apoptotic pathways. RES demonstrated a slightly superior efficacy in reducing inflammation and oxidative stress markers, suggesting it may be more effective in treating acute pancreatitis.
