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- ArticleAçık Erişim2024Effect of ethyl acetate extract from Usnea longissima on chemotherapy-associated multiple organ dysfunction in rats
Bingul, Eda; Bulut, Seval; Mammadov, Renad; Cicek, Betul; Dogru, Tugba Erkmen; Suleyman, Halis; Mendil, Ali Sefa
Background: The toxic effects of doxorubicin and cisplatin in various organs have been associated with oxidative stress. Studies have shown that Usnea longissima has strong antioxidant effects. This study aimed to investigate the protective effect of ethyl acetate extract from Usnea longissima (ULE), which is known to have strong antioxidant effects, on chemotherapeutic-induced heart, kidney, liver, and ovarian toxicity. Methods: Albino Wistar female rats were divided into five groups (12 rats per group): healthy (HG), doxorubicin (DOX), Cisplatin (CIS), Doxorubicin+ ULE (DULE), Cisplatin+ ULE (CULE). In this experiment, ULE was given 100 mg/kg orally. After 1 hour, 2.5 mg/kg doxorubicin and 2.5 mg/kg cisplatin were administered intraperitoneally. Drug treatments continued once a day for seven days. At the end of seven days, six rats from each group were euthanized and heart, kidney, liver, and ovary tissues were analyzed biochemically. The remaining rats were left in the laboratory with male rats for 45 days for reproduction. Results: ULE inhibited chemotherapeutic-induced increase in malondialdehyde, tumor necrosis factor-alpha, and interleukin 6 and a decrease in total glutathione in liver, kidney, and ovarian tissues. ULE also inhibited the increase of blood urea nitrogen, creatinine, alanine aminotransferase, and aspartate aminotransferase in serum. ULE treatment had no protective effect against doxorubicin and cisplatin cardiac toxicity. On the other hand, ULE also decreased the delay in pregnancy induced by chemotherapy. Conclusion: ULE may be considered an adjuvant therapy in patients receiving chemotherapy to reduce liver, kidney, and ovarian toxicity.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2024Morinda citrifolia protective effects on paclitaxel-induced testis parenchyma toxicity: An experimental study
Genc, Sidika; Cicek, Betul; Yeni, Yesim; Kuzucu, Mehmet; Hacimuftuoglu, Ahmet; Bolat, Ismail; Yildirim, Serkan; Zaker, Himasadat; Zachariou, Athanasios; Sofikitis, Nikolaos
The current study aimed to investigate the sensitivity of male testis parenchyma cells to chemotherapy agents and the protective effects and mechanisms of Morinda citrifolia (Noni) administration against structural and functional changes before and after chemotherapy (Paclitaxel (PTX)). For this purpose, rats were randomly assigned into four groups (Control = G1, PTX 5 mg/kg = G2; PTX + Noni 10 mg/kg = G3, PTX + Noni 20 mg/kg = G4). PTX was injected intraperitoneally for 4 consecutive weeks, at a dose of 5 mg/kg to all groups except the control group. Then noni was administrated in 10 (G3) and 20 (G4) mg/kg groups orally (gavage) for 14 days. Biochemical analyses, Real-Time Polymerase Chain Reaction (PCR), and immunohistochemical analyses were performed. According to our results, Total Oxidative Stress (TOS) and Malondialdehyde (MDA) were significantly increased in the PTX group (P < 0.01). Superoxide Dismutase (SOD) enzyme activity and Total Antioxidant Capacity (TAC) levels were decreased (P < 0.01). The changes in the rats treated with PTX + Noni 20 mg/kg were noteworthy. The increased levels of IL1-β (Interleukin 1 beta) and TNFα (tumor necrosis factor-alpha) with PTX were down-regulated after treatment with PTX + Noni 20 mg/kg (P < 0.01) (9 % and 5 % respectively). In addition, Noni restored the testicular histopathological structure by reducing caspase-3 expression and significantly (61 %) suppressed oxidative DNA damage and apoptosis (by regulating the Bax (bcl-2-like protein 4)/Bcl-2 (B-cell lymphoma gene-2) ratio). In conclusion, Noni reduced cellular apoptosis and drastically changed Caspase 8 and Bax/Bcl-2 levels. Furthermore, it considerably decreases oxidative damage and can be used in testicular degeneration.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2023Effect of Thiamine Pyrophosphate upon Possible Metamizole-Induced Liver Injury in Rats
Bedir, Zehra; Erdem, Kezban Tuna Ozkaloglu; Can, Abdullah; Cicek, Betul; Gulaboglu, Mine; Suleyman, Zeynep; Gursul, Cebrail; Mokhtare, Behzad; Ozcicek, Fatih; Suleyman, Halis
Background and Objective: Metamizole is a non-selective cyclooxygenase (COX) inhibitor NSAID with a strong analgesic and spasmolytic effects. It is the most common analgesic in the world. Thiamine pyrophosphate (TPP) protects the liver tissue against oxidative damage. The aim of our study was to analyze the effect of TPP against possible liver injury and dysfunction of metamizole in rats biochemically and histopathologically. Materials and Methods: The animals were grouped as healthy (HG), 500 mg kg(-1) metamizole (MT-500), 1000 mg kgG1 metamizole (MT-1000), 25 mg kg(-1) TPP+500 mg kg(-1) metamizole (TMT-500), 25 mg kg(-1) TPP+1000 mg kg(-1) metamizole (TMT-1000) groups. The TMT-500 and TMT-1000 groups of animals were injected intraperitoneally (ip) at the dose of 25 mg kg(-1) of TPP. Distilled water as the solvent was injected ip to the HG, MT-500 and MT-100 groups. One hour after injecting TPP and distilled water, metamizole 500 and 1000 mg kg(-1) doses were administered orally to the TMT-500 and TMT-1000 groups. The TPP was administered once and metamizole twice a day for 14 days. The animals were euthanized with high-dose anesthesia. The liver tissues excised from the animals were analyzed biochemically and histopathologically. Results: In both doses metamizole significantly increased MDA, ALT and AST levels and decreased tGSH, SOD and CAT levels compared to the healthy group. TPP significantly prevented the decrease of tGSH, SOD and CAT levels and the increase of MDA, ALT and AST levels with metamizole. There was no statistical difference in all of the levels between the TMT-500 and TMT-1000 groups. The histopathological findings indicated TPP significantly suppressed the damage induced by metamizole. Conclusion: The metamizole was possible to cause moderate damage to liver tissue. Therefore, it was considered that the use of TTP to reduce liver toxicity could be clinically beneficial.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2023Effect of Liv-52 on Atorvastatin Induced Hepatotoxicity in Rats: A Biochemical and Histopathologic Study
Icel, Aykut; Suleyman, Bahadir; Mammadov, Renad; Bulut, Seval; Cicek, Betul; Yazici, Gulce Naz; Gulaboglu, Mine; Ozcicek, Fatih; Suleyman, Halis
Background and Objective: The toxic effect of atorvastatin on the liver has been associated with oxidative stress. The Liv-52 is a polyherbal formulation with known hepatoprotective properties. In this study, the preventive effect of Liv-52 against the potential hepatotoxicity of atorvastatin was investigated. Materials and Methods: Eighteen rats were categorized into three groups of six rats each: Healthy group (HG), atorvastatin-treated group (ATC) and Liv-52+atorvastatin-treated group (LAT). The Liv-52 was orally administered at 50 mg kg(-1) and atorvastatin was orally given at 20 mg kg(-1) after 1 hr of Liv-52 administration. The Liv-52 and atorvastatin were administered once daily for two months. At the end of two months, blood samples were collected from the rats. Subsequently, rats were sacrificed under high-dose (50 mg kg(-1)) thiopental anesthesia and liver tissues were extracted. Biochemical analysis of extracted liver tissues and serum was performed. Liver tissues were additionally analyzed for histopathology. Results: The Liv-52+atorvastatin administration inhibited the atorvastatin-induced increase in malondialdehyde and decreased total glutathione and superoxide dismutase activities in the liver tissues. In addition, the rats receiving Liv-52 had lower levels of serum alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase compared to the atorvastatin group. Histopathologic analysis demonstrated that Liv-52 protected the liver tissue against atorvastatin-induced injury. Conclusion: The Liv-52 therapy may be useful in preventing atorvastatin-induced liver injury.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2023Carnosic Acid Ameliorates Indomethacin-Induced Gastric Ulceration in Rats by Alleviating Oxidative Stress and Inflammation
Danisman, Betul; Cicek, Betul; Yildirim, Serkan; Bolat, Ismail; Kantar, Deniz; Golokhvast, Kirill S.; Nikitovic, Dragana; Tsatsakis, Aristidis; Taghizadehghalehjoughi, Ali
Nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin and indomethacin (IND) are the most commonly prescribed for inflammation or pain. However, widespread use causes several adverse effects, such as gastric ulcers, upper gastric system bleeding, and erosions. Carnosic acid (CA) is an important natural antioxidant found in rosemary (Rosmarinus essentials) and exhibits a protective effect by suppressing oxidative stress and inflammation. This study aimed to investigate the impact of CA on IND-induced gastric ulceration. Wistar male rats received CA (100 mg/kg) or esomeprazole (ESP) (20 mg/kg, standard drug) by oral gavage for 14 days, after that gastric ulceration was induced by oral administration of 100 mg/kg IND. CA pretreatment attenuated both gross morphological lesions and histopathological alterations. CA strongly reduced IND-induced oxidative stress, verified by a decrease in MDA (p < 0.001) and TOS levels (p < 0.05). Furthermore, an IND-dependent increase in CAT (p < 0.001) and GPx (p < 0.01) activities, as well as a reduction in GSH levels (p < 0.01), were ameliorated by CA pretreatment. CA also attenuated inflammatory damage by suppressing IL-1β (p < 0.01), IL-6 (p < 0.01), and TNFα (p < 0.001) production and increasing Nrf2/HO-1 (p < 0.05) expressions. In conclusion, CA shows a gastroprotective effect by reducing oxidative stress and attenuating inflammation.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2023Carvacrol prevents acrylamide-induced oxidative and inflammatory liver damage and dysfunction in rats
Cerrah, Serkan; Ozcicek, Fatih; Gundogdu, Betul; Cicek, Betul; Coban, Taha Abdulkadir; Suleyman, Bahadir; Altuner, Durdu; Bulut, Seval; Suleyman, Halis
Background: Acrylamide causes hepatotoxicity with the effect of oxidative stress and inflammatory processes. Carvacrol is a monoterpenic phenol with antioxidant and anti-inflammatory properties. Aims: To determine the effects of carvacrol on oxidative liver injury induced by acrylamide administration in rats. Methods: Rats were divided into three groups of six animals each: healthy group acrylamide group (ACR), and acrylamide + carvacrol group (TACR). First, carvacrol (50 mg/kg) was administered intraperitoneally to the CACR group. One hour later, acrylamide (20 mg/kg) was given orally to the ACR and CACR groups. This procedure was performed for 30 days, after which the animals were sacrificed. The malondialdehyde (MDA) and total glutathione (tGSH) levels, total oxidant (TOS) and total antioxidant status (TAS), tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), and nuclear factor kappa b (NF-κB) were measured in the excised liver tissues. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were determined in blood serum samples. Liver tissues were also examined histopathologically. Results: In the ACR group, malondialdehyde, TOS, ALT, AST levels, and NF-κB, IL-1β, and TNF-α levels were found to be high, and tGSH and total antioxidant status levels were low. In addition, diffuse degenerative changes and necrosis in hepatocytes, and moderate inflammation in the portal region were detected in the liver tissues of the ACR group. While carvacrol prevented the biochemical changes induced by acrylamide, it also alleviated the damage in the histological structure. Conclusion: Carvacrol may be used for liver damage caused by acrylamide.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2023Effect of anakinra, tocilizumab, and the combination thereof on bladder ischemia-reperfusion damage in albino Wistar-type rats; [Efecto de la anakinra, el tocilizumab y la combinación de ambos sobre el daño por isquemia-reperfusión vesical en ratas albinas tipo Wistar]
Bicer, Senol; Suleyman, Bahadir; Mammadov, Renad; Yavuzer, Bulent; Cicek, Betul; Altuner, Durdu; Coban, Taha A.; Suleyman, Halis
Several studies have reported that oxidative stress, and proinflam-matory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-one beta (IL-1β), and interleukin-six (IL-6) are the main factors underlying bladder ischemia-reperfusion (I/R) damage. Anakinra and tocilizumab are known to be antioxidants and proinflammatory cytokine inhibitors. Our study aims to investigate if anakinra, tocilizumab, and the combination (ATC) thereof have a protective effect against oxidative and inflammatory bladder damage induced through the I/R procedure in rats, and evaluate by comparing these compounds. Male rats were divided into five groups: bladder sham-operation applied group (SG); bladder only I/R applied group (IRG); anakinra+bladder I/R applied group (AIR); tocilizumab+bladder I/R applied group (TIR); and ATC+bladder I/R applied group (ATIR). An atraumatic clamp was placed on the abdominal aorta of animals in all groups (except SG), and one hour of ischemia followed by two hours of reperfusion was performed. Our biochemical find-ings showed that anakinra and tocilizumab significantly inhibited the increase of oxidant malondialdehyde (MDA) and the decrease of antioxidants such as total glu-tathione (tGSH), superoxide dismutase (SOD), and catalase (CAT) in bladder tissue by I/R, both at the same levels. Furthermore, anakinra and tocilizumab significantly suppressed the I/R-associated increase of TNF-α, IL-1β, and IL-6 in bladder tissue. ATC was the one that best prevented the I/R-related increase in MDA, TNF-α, IL-1β, and IL-6 and the decrease in tGSH, SOD, and CAT in the bladder tissue. ATC was more beneficial than anakinra or tocilizumab alone in treating bladder I/R damage.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2023Effects of benidipine, paracetamol, and their combination on postoperative and normal tissue pain thresholds
Bedir, Zehra; Ozkaloglu Erdem, Kezban Tuna; Doymus, Omer; Suleyman, Halis; Yavuzer, Bulent; Cicek, Betul; Altuner, Durdu; Mammadov, Renad; Yilmaz, Mehmet; Coban, Taha Abdulkadir
Introduction: In clinical practice, inadequate pain inhibition leads to increased morbidity and mortality. Increased intracellular calcium, oxidants, and proinflammatory cytokines are known to play a role in the pathogenesis of postoperative pain. Therefore, we investigated the analgesic effects of benidipine, paracetamol, and benidipine-paracetamol combination (BPC) on postoperative and normal pain thresholds in rats. Material and methods: Sixty-four male albino Wistar rats weighing 285–295 g were used. The without-incision rats were divided into 4 subgroups: healthy control, benidipine alone, paracetamol alone, and BPC. The scalpel-incision rats were divided into 4 subgroups: scalpel incision, scalpel incision + benidipine, scalpel incision + paracetamol, and scalpel incision + BPC. Paw pain thresholds of rats were measured using a Basile algesimeter. Biochemical analyses were performed on the paw tissues of 6 rats randomly taken from the experimental groups, each containing 8 rats. Rats were sacrificed immediately after the measurements. After the pain threshold tests were finished, the paw tissues were removed and malondialdehyde (MDA), total glutathione (tGSH), cyclooxygenase (COX), and interleukin-6 (IL-6) levels were measured. Results: There was no significant difference between the groups in paw pain threshold and measured biochemical parameters in rats without incision. The decrease in the pain threshold of the incised paw was also best prevented by BPC, followed by benidipine and then paracetamol. Furthermore, increases in scalpel-incised paw tissue MDA, COX-2, and IL-6 levels and the decrease in tGSH were significantly suppressed by benidipine and BPC, while paracetamol could only significantly inhibit the increase in IL-6 production. Conclusion: The combination of the L-type Ca2+ channel blocker benidipine and paracetamol (BPC) may provide potent analgesia. Our experimental results support that BPC may be useful in the treatment of severe pain that cannot be adequately inhibited by paracetamol.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2023Chlorogenic Acid Attenuates Doxorubicin-Induced Oxidative Stress and Markers of Apoptosis in Cardiomyocytes via Nrf2/HO-1 and Dityrosine Signaling
Cicek, Betul; Hacimuftuoglu, Ahmet; Yeni, Yesim; Danisman, Betul; Ozkaraca, Mustafa; Mokhtare, Behzad; Kantarci, Mecit; Spanakis, Marios; Nikitovic, Dragana; Lazopoulos, Georgios
(1) Background: Doxorubicin (DOX) is extensively used for cancer treatments; however, its clinical application is limited because of its cardiotoxic adverse effects. A combination of DOX and agents with cardioprotective properties is an effective strategy to ameliorate DOX-related cardiotoxicity. Polyphenolic compounds are ideal for the investigation of novel cardioprotective agents. Chlorogenic acid (CGA), an essential dietary polyphenol found in plants, has been previously reported to exert antioxidant, cardioprotective, and antiapoptotic properties. The current research evaluated CGA’s in vivo cardioprotective properties in DOX-induced cardiotoxicity and the probable mechanisms underlying this protection. (2) Methods: CGA’s cardioprotective properties were investigated in rats that were treated with CGA (100 mg/kg, p.o.) for fourteen days. The experimental model of cardiotoxicity was induced with a single intraperitoneal (15 mg/kg i.p.) injection of DOX on the 10th day. (3) Results: Treatment with CGA significantly improved the DOX-caused altered cardiac damage markers (LDH, CK-MB, and cTn-T), and a marked improvement in cardiac histopathological features accompanied this. DOX downregulated the expression of Nrf2/HO-1 signaling pathways, and the CGA reversed this effect. Consistently, caspase-3, an apoptotic-related marker, and dityrosine expression were suppressed, while Nrf2 and HO-1 expressions were elevated in the cardiac tissues of DOX-treated rats after treatment with the CGA. Furthermore, the recovery was confirmed by the downregulation of 8-OHdG and dityrosine (DT) expressions in immunohistochemical findings. (4) Conclusions: CGA demonstrated a considerable cardioprotective effect against DOX-induced cardiotoxicity. One of the possible mechanisms for these protective properties was the upregulation of the Nrf2/HO-1-dependent pathway and the downregulation of DT, which may ameliorate oxidative stress and cardiomyocyte apoptosis. These findings suggest that CGA may be cardioprotective, particularly in patients receiving DOX-based chemotherapy.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2023Sorafenib Alleviates Inflammatory Signaling of Tumor Microenvironment in Precancerous Lung Injuries
Cicek, Betul; Hacimuftuoglu, Ahmet; Kuzucu, Mehmet; Cetin, Ahmet; Yeni, Yesim; Genc, Sidika; Yildirim, Serkan; Bolat, Ismail; Kantarci, Mecit; Gul, Mustafa
According to population-based studies, lung cancer is the prominent reason for cancer-related mortality worldwide in males and is also rising in females at an alarming rate. Sorafenib (SOR), which is approved for the treatment of hepatocellular carcinoma and renal cell carcinoma, is a multitargeted protein kinase inhibitor. Additionally, SOR is the subject of interest for preclinical and clinical trials in lung cancer. This study was designed to assess in vivo the possible effects of sorafenib (SOR) in diethylnitrosamine (DEN)-induced lung carcinogenesis and examine its probable mechanisms of action. A total of 30 adult male rats were divided into three groups (1) control, (2) DEN, and (3) DEN + SOR. The chemical induction of lung carcinogenesis was performed by injection of DEN intraperitoneally at 150 mg/kg once a week for two weeks. The DEN-administered rats were co-treated with SOR of 10 mg/kg by oral gavage for 42 alternate days. Serum and lung tissue samples were analyzed to determine SRY-box transcription factor 2 (SOX-2) levels. The tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) levels were measured in lung tissue supernatants. Lung sections were analyzed for cyclooxygenase-2 (COX-2) and c-Jun N-terminal kinase (JNK) histopathologically. In addition, cyclooxygenase-2 (COX-2) and c-Jun N-terminal kinase (JNK) were analyzed by immunohistochemistry and immunofluorescence methods, respectively. SOR reduced the level of SOX-2 that maintenance of cancer stemness and tumorigenicity, and TNF-α and IL-1β levels. Histopathological analysis demonstrated widespread inflammatory cell infiltration, disorganized alveolar structure, hyperemia in the vessels, and thickened alveolar walls in DEN-induced rats. The damage was markedly reduced upon SOR treatment. Further, immunohistochemical and immunofluorescence analysis also revealed increased expression of COX-2 and JNK expression in DEN-intoxicated rats. However, SOR treatment alleviated the expression of these inflammatory markers in DEN-induced lung carcinogenesis. These findings suggested that SOR inhibits DEN-induced lung precancerous lesions through decreased inflammation with concomitant in reduced SOX-2 levels, which enables the maintenance of cancer stem cell properties.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2023Taxifolin as a novel therapeutic agent for epileptic seizures induced by caffeine-induced oxidative stress in rats
Yasar, Hasan; Altuner, Durdu; Bulut, Seval; Cicek, Betul; Gursul, Cebrail; Kuzucu, Mehmet; Suleyman, Halis
Background. Epilepsy is a severe neurological disease that results from excessive and/or synchronized neuronal activity in the brain, and oxidative stress plays a role in its pathogenesis. Taxifolin is a flavonoid that exhibits antioxidant activity. Objectives. To investigate the effects of taxifolin on caffeine-induced epileptic seizures in rats and reveal the role of antioxidant activity in antiepileptic therapy. Materials and methods. Forty rats were divided into 4 groups (n = 6/group): caffeine 300 mg/kg group (CG), taxifolin 50 mg/kg + caffeine 300 mg/kg group (TCG), 2 mg/kg diazepam + 300 mg/kg caffeine group (DCG), and a healthy group (HG). Taxifolin was given to the TCG, and diazepam was given to the DCG orally. One hour later, caffeine was injected intraperitoneally into the CG, TCG and DCG rats. The time between the caffeine injection and the contractions (the latency period) was determined. Animals were euthanized 1 h after caffeine injection, and brain tissues were biochemically examined for oxidants and antioxidants. Results. Taxifolin and diazepam prolonged the latency period to a similar extent (p = 0.549), while taxifolin was more successful in preventing mortality. Taxifolin suppressed the caffeine-induced increase in myeloperoxidase, total oxidant status and oxidative stress index, and decreased total glutathione, superoxide dismutase and total antioxidant status more effectively than diazepam (p < 0.05). Conclusions. We showed the relationship between antioxidant activity and epilepsy treatment, and demonstrated that taxifolin may be useful for treating epilepsy.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2023Protective Effect of Adenosine Triphosphate against 5-Fluorouracil-Induced Oxidative Ovarian Damage in vivo
Ozer, Mehmet; Ince, Sefa; Altuner, Durdu; Suleyman, Zeynep; Cicek, Betul; Gulaboglu, Mine; Mokhtare, Behzad; Gursul, Cebrail; Suleyman, Halis
Objective: The aim of our study was to analyze the effect of ATP on possible ovarian damage of 5-FU in rats. Methods: The animals were divided to three groups; healthy group (HG), 5-FU alone group (FUG) and ATP+5-FU administered group (AFU). The ATP 4 mg/kg was injected intraperitoneally (IP) into the AFU group. The same volume of saline (0.9% NaCl) as the solvent was administered intraperitoneally to the HG and FUG groups. One hour after administering ATP and solvent, 5-FU 100 mg/kg was injected intraperitoneally to the animals in the AFU and FUG groups. ATP was administered to the animals once a day for 10 days. On the 1st, 3rd and 5th days of 5-FU, one dose (total of 3 doses) was administered. On day 10, the animals were euthanasia with high-dose anaesthesia and ovarian tissues were removed. The removed ovaries were analyzed biochemically andhistopathological. Result: ATP significantly suppressed both the increase in MDA and IL-6 levels, and the decrease in tGSH, SOD and CAT levels. Treatment with ATP significantly suppressed the severe vacuolization and primordial follicle degeneration induced by 5-FU in our study. Conclusion: ATP was possible to be useful for the treatment of 5-FU-induced ovarian damage.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2023Bromelain protects against cisplatin-induced ocular toxicity through mitigating oxidative stress and inflammation
Ferah Okkay, Irmak; Okkay, Ufuk; Bayram, Cemil; Cicek, Betul; Sezen, Selma; Aydin, Ismail Cagri; Mendil, Ali Sefa; Hacimuftuoglu, Ahmet
The aim of this study was to investigate the molecular, biochemical, and histopathological effects of bromelain, which has antioxidant and anti-inflammatory properties, against cisplatin-induced ocular toxicity. The groups were designed as (1) Control, (2) Cisplatin (7 mg/kg, intraperitoneally), (3) Cisplatin + Bromelain (50 mg/kg, orally for 14 consecutive days), (4) Cisplatin + Bromelain (100 mg/kg, orally for 14 consecutive days). The activity of total antioxidant capacity (TAC) and total oxidant status (TOS) and levels of reactive oxygen species (ROS), superoxide dismutase (SOD), malondialdehyde (MDA), interleukin-1β (IL-1β), IL-10, nuclear factor kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α) and 8-OHdG were measured in ocular tissue. The mRNA expression of NF-κB and Caspase-3 was also evaluated. Also, ocular sections were evaluated histopathologically. Bromelain demonstrated a dose-dependent protective effect in cisplatin-induced toxicity by regulating oxidative stress, inflammation, and tissue damage. Our results suggested that bromelain may be a potential adjuvant that can protect the eye from cisplatin-induced toxicity.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2023Flavonoid-Rich Sambucus nigra Berry Extract Enhances Nrf2/HO-1 Signaling Pathway Activation and Exerts Antiulcerative Effects In Vivo
Cicek, Betul; Danısman, Betul; Yildirim, Serkan; Yuce, Neslihan; Nikitovic, Dragana; Bolat, Ismail; Kuzucu, Mehmet; Ceyran, Ertuğrul; Bardas, Ebru; Golokhvast, Kirill S.
Sambucus nigra (SN) berry extract is characterized by high antioxidant and anti-inflammatory activity. The current study aimed to investigate the effect of SN berry extract against indomethacin (IND)-induced gastric ulcer in rats and the mechanism involved. SN berry extract alleviated IND-induced gastric ulcers, as shown by assessing pathological manifestations in the gastric mucosa. These protective effects are attributed to attenuated oxidative damage to the gastric mucosa, correlated to increased activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), enhanced glutathione (GSH) levels, total antioxidant capacity (TAC), and upregulation of the Nrf2/HO-1 cascade. Moreover, oxidative stress markers, including malondialdehyde (MDA) and total oxidant status (TOS), were downregulated in SN-extract-treated animals. Furthermore, SN berry extract suppressed gastric mucosal inflammation by downregulating interleukin (IL)-33, IL-1β, IL-6, and tumor necrosis factor-alpha (TNF-α) levels, and attenuating myeloperoxidase (MPO) activity. The protective effects of SN berry extract were similar to those exerted by esomeprazole (ESO), an acid-secretion-suppressive drug. In conclusion, SN berry extract has antiulcerative effects, alleviating oxidative stress and inflammation.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2022Hepatoprotective and neuroprotective effect of taxifolin on hepatic encephalopathy in rats
Okkay, Ufuk; Ferah Okkay, Irmak; Cicek, Betul; Aydin, Ismail Cagri; Ozkaraca, Mustafa
This study was planned to assess the potential protective effects of taxifolin against thioacetamide-induced hepatic encephalopathy and subsequently to portray its behavioural results. The experimental model was induced with three doses of (200 mg/kg i.p.) thioacetamide and taxifolin (50 and 100 mg/kg, p.o.) was administered for fourteen days. Taxifolin effectively attenuated hepatic encephalopathy through decrease in AST, ALT, ALP and LDH concentrations and improvement of hyperammonemia, and increase in antioxidant capacity by decreasing MDA, ROS, and increasing CAT and GSH. In addition, the expressions of NF-κB, TNF-α, IL-1β, caspase-3 and Bax was down-regulated while IL-10 and Bcl-2 expressions were up-regulated with taxifolin treatment. The recovery was confirmed by downregulation of iNOS and 8-OHdG expressions in our immunohistochemical analysis. Taxifolin treatment reduced the disrupting role of thioacetamide as seen by corrected hyperammonemia as well as preservation of astrocyte and hepatocyte structure. Elevated plus maze and locomotor activity tests also proved that taxifolin might repeal the neurobehavioral disabilities. In conclusion, taxifolin has shown hepatoprotective and neuroprotective roles with antioxidant and anti-inflammatory effects, as well as suppressing the excessive release of ammonia, and it eventually reversed neurobehavioral impairments. Graphical abstract: [Figure not available: see fulltext.].
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2022Artichoke (Cynara Scolymus) Methanolic Leaf Extract Alleviates Diethylnitrosamine-Induced Toxicity in BALB/c Mouse Brain: Involvement of Oxidative Stress and Apoptotically Related Klotho/PPARγ Signaling
Cicek, Betul; Genc, Sidika; Yeni, Yesim; Kuzucu, Mehmet; Cetin, Ahmet; Yildirim, Serkan; Bolat, Ismail; Kantarci, Mecit; Hacimuftuoglu, Ahmet; Lazopoulos, Georgios
(1) Background: Various epidemiological studies suggest that oxidative stress and disrupted neuronal function are mechanistically linked to neurodegenerative diseases (NDs), including Parkinson’s disease (PD) and Alzheimer’s disease (AD). DNA damage, oxidative stress, lipid peroxidation, and eventually, cell death such as NDs can be induced by nitrosamine-related compounds, leading to neurodegeneration. A limited number of studies have reported that exposure to diethylnitrosamine (DEN), which is commonly found in processed/preserved foods, causes biochemical abnormalities in the brain. Artichoke leaves have been used in traditional medicine as a beneficial source of bioactive components such as hydroxycinnamic acids, cynarine, chlorogenic acid, and flavonoids (luteolin and apigenin). The aim of this study is to investigate the favorable effects of exogenous artichoke (Cynara scolymus) methanolic leaf extract supplementation in ameliorating DEN-induced deleterious effects in BALB/c mouse brains. (2) Methods: This study was designed to evaluate DEN (toxicity induction by 100 mg/kg) and artichoke (protective effects of 0.8 and 1.6 g/kg treatment) for 14 days. All groups underwent a locomotor activity test to evaluate motor activity. In brain tissue, oxidative stress indicators (TAC, TOS, and MDA), Klotho and PPARγ levels, and apoptotic markers (Bax, Bcl-2, and caspase-3) were measured. Brain slices were also examined histopathologically. (3) Results: Artichoke effectively ameliorated DEN-induced toxicity with increasing artichoke dose. Impaired motor function and elevated oxidative stress markers (decreasing MDA and TOS levels and increasing TAC level) induced by DEN intoxication were markedly restored by high-dose artichoke treatment. Artichoke significantly improved the levels of Klotho and PPARγ, which are neuroprotective factors, in mouse brain tissue exposed to DEN. In addition, caspase-3 and Bax levels were reduced, whereas the Bcl-2 level was elevated with artichoke treatment. Furthermore, recovery was confirmed by histopathological analysis. (4) Conclusions: Artichoke exerted neuroprotective effects against DEN-induced brain toxicity by mitigating oxidant parameters and exerting antioxidant and antiapoptotic effects. Further research is needed to fully identify the favorable impact of artichoke supplementation on all aspects of DEN brain intoxication.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2021Neuroprotective effect of bromelain in 6-hydroxydopamine induced in vitro model of Parkinson’s disease
Ferah Okkay, Irmak; Okkay, Ufuk; Cicek, Betul; Yilmaz, Aysegul; Yesilyurt, Fatma; Mendil, Ali Sefa; Hacimuftuoglu, Ahmet
Background: This study was designed to investigate the neuroprotective effects of bromelain, which is known to have anti-oxidant and anti-inflammatory properties, against the neurotoxicity (induced by 6-OHDA) in SH-SY5Y cells. Methods and results: To establish Parkinson’s Disease (PD) model in cell culture conditions, SH-SY5Y cells were exposed to 200 µM 6-OHDA for 1 day. Prior to 6-OHDA treatment, SH-SY5Y cells had been pre-treated with bromelain (25 µg/mL, 50 µg/mL, 75 µg/mL and 100 µg/mL). After 1 day, cell viability was determined with the 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) and lactate dehydrogenase (LDH) assays. Oxidative stress was assessed with total antioxidant capacity (TAC), total oxidant status (TOS), glutathione reductase (GR) and malondialdehyde (MDA) analyses. The effect of the bromelain in SH-SY5Ycells was also examined by 4′,6-diamidino-2-phenylindole (DAPI) staining. We found that 6-OHDA increased LDH leakage, and cellular apoptosis in SH-SY5Y cells. 6-OHDA aggravated oxidative stress by increasing TOS, MDA and GR and eventually promoted apoptosis in SH-SY5Y cells, while pretreatment with bromelain attenuated these toxic effects of 6-OHDA. Conclusions: These findings indicated that bromelain, with its neuroprotective features can be useful for neuroprotection in PD.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2021Achillea millefolium alleviates testicular damage in paclitaxel-intoxicated rats via attenuation of testicular oxido-inflammatory stress and apoptotic responses
Okkay, Ufuk; Ferah Okkay, Irmak; Cicek, Betul; Aydin, Ismail Cagri; Ertugrul, Muhammed Sait; Bayram, Cemil; Senyayla, Selcuk; Sezen, Selma; Mendil, Ali Sefa; Guven, Leyla
The aim of this study was to investigate the effects of Achillea millefolium extract in paclitaxel-induced testicular toxicity in rats. The groups were designed as (1) control, (2) paclitaxel (8 mg/kg, intraperitoneally), (3) paclitaxel (8 mg/kg, intraperitoneally) + Achillea millefolium (200 mg/kg, orally for 14 consecutive days) and (4) paclitaxel (8 mg/kg, intraperitoneally) + Achillea millefolium (400 mg/kg, orally for 14 consecutive days). Serum levels of testosterone, luteinising hormone and follicle-stimulating hormone, as well as total antioxidant capacity and total oxidant status were measured one day after receiving the last dose of Achillea millefolium extract. Testicular superoxide dismutase activity, malondialdehyde, tumour necrosis factor alpha and interleukin-1β levels, the expressions of nuclear factor kappa B and caspase-3 were evaluated. In addition, testicular sections were evaluated histopathologically and 8-hydroxy-2′-deoxyguanosine was detected immunohistochemically. Achillea millefolium improved the levels of luteinising hormone, follicle-stimulating hormone and testosterone, upregulated testicular antioxidant enzymes and downregulated inflammation. Furthermore, we observed that Achillea millefolium restored testicular histopathological structure and significantly suppressed oxidative DNA damage and apoptosis by reducing the expression of caspase-3. Taken together, our results suggest that Achillea millefolium has protective effects against paclitaxel-induced testicular toxicity and is a promising natural product with the potential to improve male fertility.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2020Vitamin e and Selenium Reduce Prednisolone Side Effects in Rat Hearts
Bardas, Ebru; Arslan, Yusuf Kemal; Polat, Seher; Erisir, Mine; Uslu, Gözde Atila; Cetin, Nihal; Cicek, Betul
Aim of this work was to determine the effects of dietary intake vitamin E and Se on lipid peroxidation (LPO) as Thiobarbituric acid reactive substances (TBARS) and on the antioxidative defense mechanisms in heart tissues of rats treated with high doses of prednisolone. 250 adult male Wistar rats were randomly divided into 5 groups and fed with normal diet. Additionally groups 3, 4, and 5 received a daily supplement in their drinking water of 20 mg vitamin E, 0.3 mg Se, and a combination of vitamin E and Se (20 mg/0.3 mg), respectively, for 30 days. For 3 d subsequently, control group was treated with placebo, and remaining four groups were injected intramuscularly with 100 mg/kg prednisolone. After last administration of prednisolone, 10 rats from each group were killed at 4, 8, 12, 24, and 48 h and the activities of antioxidant enzymes and the levels of GSH and TBARS were measured. GSH-Px, CAT activities and GSH levels decreased starting from 4th hour to 48% and 65% of control levels by 24th hour, respectively and it reincreased to control levels at 48th hour in the prednisolone group (p < 0.001, p < 0.001). In addition, prednisolone administration led 2-fold increase in heart TBARS levels at 24th hour (p < 0.001). E vitamins and Se inhibited the increase in heart TBARS and the decrease in antioxidative enzymes levels. Therefore, It is concluded that vitamin E and Se may have a preventive role in decreasing the increase of TBARS caused by prednisolone administration in our study.
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