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- ArticleYalnız künye2024Effects of carvacrol on ketamine-induced cardiac injury in rats: an experimental study
Ölmeztürk Karakurt, Tülay Ceren; Emir, İzzet; Bedir, Zehra; Ozkaloglu Erdem, Kezban Tuna; Süleyman, Halis; Sarıgül, Cengiz; Mendil, Ali Sefa
Aim: We aimed to investigate the preventive effects of carvacrol against ketamine-induced cardiotoxicity biochemically and histopathologically in an experimental model. Material and method: The rats were divided into three groups; healthy control (HC), ketamine alone (KG), and ketamine + carvacrol (KCG) groups. Serum Creatine Kinase Myocardial Band (CK-MB) and Troponin I (TP I) levels were determined. Malondialdehyde (MDA), Glutathione (GSH), Superoxide Dismutase (SOD), Tumor Necrosis Factor α (TNF-α), Interleukin 1 beta (IL-1beta), and Interleukin 6 (IL-6) levels were measured in the heart tissues of the rats. Heart tissues were also evaluated histopathologically. Results: In the ketamine-treated group, tissue MDA, TNF-α, IL-1beta, and IL-6 levels increased while tissue GSH and SOD levels decreased significantly compared with the control group. However, in the ketamine plus carvacrol applied group, all those alterations were significantly less pronounced, close to the healthy controls. Severe mononuclear cell infiltrations, degenerated myocytes and hemorrhage were determined in the ketamine alone administered group, and these alterations were at a mild level in the carvacrol + ketamine administered group. Conclusion: Prolonged exposure to ketamine resulted in induced oxidative stress in rat heart tissue; concomitant carvacrol application could counteract the negative effects of ketamine by protecting tissues from lipid peroxidation and decreasing the inflammatory response.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2024Hepatoprotective effects of resveratrol on α-amanitin-induced liver toxicity in rats
Gezer, Arzu; Ustundag, Hilal; Mendil, Ali Sefa; Bedir, Gursel; Duysak, Lale
Objective: The hepatoprotective effects of resveratrol against α-Amanitin (α-AMA)-induced liver toxicity were investigated in an experimental rat model, focusing on oxidative stress, inflammation, apoptosis, and liver function. Methods: Thirty-two male Sprague-Dawley rats were divided into four groups (n = 8 per group): Control, resveratrol, α-AMA, and resveratrol+α-AMA. The resveratrol group received 20 mg/kg resveratrol orally for 7 days. The α-AMA group received 3 mg/kg α-AMA intraperitoneally on the 8th day. The resveratrol+α-AMA group received 20 mg/kg resveratrol orally (7 days) followed by 3 mg/kg α-AMA intraperitoneally on the 8th day. Liver tissues and blood samples were collected 48 h after α-amanitin administration for histopathological, immunohistochemical (NFkB, LC3B), and biochemical analyses (GSH, MDA, CAT, GPx, MPO, NOS, AST, ALT). Results: α-AMA significantly increased AST and ALT levels, oxidative stress marker (MDA), and inflammatory marker (MPO), while reducing antioxidant levels (GSH, CAT, GPx) and NOS concentration (P < 0.001 for all parameters). Histopathological analysis showed severe liver damage with increased NFkB and LC3B expression. resveratrol treatment significantly reduced AST and ALT levels (P < 0.01 for both parameters), decreased MDA and MPO levels, and increased NOS concentration, GSH, CAT, and GPx levels (P < 0.05 for all parameters). Reduced NFkB and LC3B expression in the resveratrol+α-AMA group and showed histopathological improvements. Conclusion: Resveratrol demonstrated substantial hepatoprotective effects against α-AMA induced liver toxicity by reducing oxidative stress, inflammation, and apoptosis, and improving liver function. These findings suggest that resveratrol could be a potential therapeutic agent for treating liver damage caused by potent hepatotoxins like α-AMA.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2024β-carotene protects against α-amanitin nephrotoxicity via modulation of oxidative, autophagic, nitric oxide signaling, and polyol pathways in rat kidneys
Gezer, Arzu; Üstündağ, Hilal; Karadağ Sarı, Ebru; Bedir, Gürsel; Gür, Cihan; Mendil, Ali Sefa; Duysak, Lale
Alpha-amanitin (α-AMA), a toxic component of Amanita phalloides, causes severe hepato- and nephrotoxicity. This study investigated the protective effects of βeta-carotene (βC) against α-AMA-induced kidney damage in rats. Thirty-two male Sprague-Dawley rats were divided into four groups: Control, βC (50 mg/kg/day), α-AMA (3 mg/kg), and βC+α-AMA. βC was administered orally for 7 days before α-AMA injection. Renal function, oxidative stress markers, histopathological changes, and enzyme activities were evaluated 48 h post-α-AMA administration. α-AMA significantly increased serum creatinine and urea levels, decreased glutathione and catalase activity, and increased malondialdehyde levels (P < 0.001). βC pretreatment attenuated these changes (P < 0.05). Histopathological examination revealed reduced tubular degeneration in the βC+α-AMA group (P < 0.001). Immunohistochemical analysis showed increased LC3B and Beclin-1 expression in α-AMA-treated rats, indicating enhanced autophagy, partially reversed by βC. Additionally, α-AMA reduced nitric oxide synthase (NOS) activity and increased aldose reductase (AR) activity, both normalized by βC pretreatment (P < 0.01). βC demonstrates protective effects against α-AMA-induced nephrotoxicity through antioxidant action, modulation of autophagy, and regulation of NOS and AR pathways, suggesting its potential as a therapeutic agent in α-AMA poisoning.
RDL Kalıcı Kaydıİncele - 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 - 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 Erişim2022Effect of tocilizumab on ischemia-reperfusion-induced oxido-inflammatory renal damage and dysfunction in rats
Erdem, Kezban Tuna Ozkaloglu; Bedir, Zehra; Kuyrukluyildiz, Ufuk; Tas, Hakan Gokalp; Suleyman, Zeynep; Bulut, Seval; Mendil, Ali Sefa; Sarigul, Cengiz; Unver, Edhem; Suleyman, Halis
Ischemia-reperfusion-induced (I/R) renal damage is a pathogenic process that starts with ischemia, then progresses through oxidative stress and inflammation. Tocilizumab (TCZ), a recombinant human monoclonal antibody produced against the IL-6 receptor, will be tested against renal I/R injury. TCZ is known to lower the levels of proinflammatory cytokines and oxidant mediators while raising the amounts of antioxidant molecules. Our purpose is to evaluate the biochemical and histological effects of TCZ against I/R-induced oxido-inflammatory kidney damage and dysfunction in rats. Animals were divided into 3 groups as renal I/R (RIR), I/R+ TCZ (IRT), and healthy group (HG). TCZ was administered at a dose of 8 mg/kg to the IRT group (n=6) of the animals, and distilled water as a solvent was administered intraperitoneally (ip) to the RIR (n=6) and HG (n=6) groups. Then, two hours of ischemia and six hours of reperfusion were applied to the left kidneys of IRT and RIR animals. TCZ significantly inhibited the increase in the levels of malondialdehyde (MDA), nuclear kappa B (NF-κB), tumour necrosis factor alpha (TNF-α), interleukin 1-β (IL-1β), IL-6, creatinine (Cr) and blood urea nitrogen (BUN) and decrease in total glutathione (tGSH) with I/R in renal tissue. TCZ also attenuated severe histopathological damage due to I/R in renal tissue. TCZ protected renal tissue from I/R-induced oxidative and inflammatory damage. These results indicate that TCZ may be useful in the treatment of renal I/R injury.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2022Effect of taxifolin on methotrexate-induced oxidative and inflammatory oral mucositis in rats: biochemical and histopathological evaluation
Bayramoglu, Zeynep; Mokhtare, Behzad; Mendil, Ali Sefa; Coban, Taha Abdulkadir; Mammadov, Renad; Bulut, Seval; Suleyman, Zeynep; Suleyman, Halis
The role of oxidative stress, as well as inflammation in the pathogenesis of methotrexate (MTX)-induced oral mucositis, is a known fact. The anti-inflammatory, antitumor, antimicrobial, and antioxidant properties of taxifolin—the effect we tested against MTX-induced oral mucosal damage—are well known. Objective: Evaluating biochemically and histopathologically the effects of taxifolin on methotrexate-induced oral mucosal damage in rats. Methodology: In the taxifolin+MTX (TMTX) group, 50 mg/kg taxifolin was orally administered to rats by gavage. In the MTX and healthy (HG) groups, normal saline was applied to rats as solvent by the same method. One hour after administration of taxifolin and solvent, 5 mg/kg MTX was orally administered to rats in the MTX and TMTX groups. Taxifolin and methotrexate were administered once a day for 30 days. Macroscopic, biochemical, and histopathological evaluations were performed on the inner cheek and tongue tissues of rats. These parts were removed after rats were killed with a high-dose anesthesia. Results: Taxifolin with MTX prevented the increase in oxidant and pro-inflammatory parameters, such as malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), interleukin 6 (IL-6), on the inner cheek and tongue tissues of rats. Moreover, taxifolin antagonized the decrease in total glutathione (tGSH). Taxifolin decreased MTX-induced histopathological damage. Conclusion: These findings suggest that taxifolin may be useful to treat MTX-associated oral mucositis.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2022THE EFFECT OF CARVACROL UPON EXPERIMENTALLY INDUCED DIABETIC NEUROPATHY AND NEUROPATHIC PAIN IN RATS
Ekinci, Bilge; Suleyman, Bahadir; Mammadov, Renad; Gezer, Arzu; Mendil, Ali Sefa; Akbas, Nergis; Bulut, Seval; Dal, Cagatay Nusret; Suleyman, Halis
Diabetic neuropathies are the most frequent complication of diabetes. While numerous metabolic pathways are disrupted in diabetic neuropathy, oxidative stress has been indicated as a significant reason for this condition. In this study, the effect of carvacrol, which has antioxidant effects, on experimental diabetic neuropathy and neuropathic pain was investigated. Alloxan was used to induce diabetes in the experiment. Diabetes was created by administering 120 mg/kg of alloxan intraperitoneally (i.p) once a day for 3 days. Rats with a blood glucose concentration above 250 mg/kg in the blood taken from the tail veins at the end of three days were considered diabetic. Rats were categorized under healthy control (HG), alloxan-induced hyperglycemia (AG), and alloxan-induced hyperglycemia + carvacrol-treated (ACG) groups. Carvacrol was i.p injected at 50 mg/kg dose to the ACG (n = 6) group of rats with hyperglycemia. The same volume of distilled water as the solvent was applied in the same way to AG (n = 6) and HG (n = 6) rat groups. This procedure was repeated once a day for three months. Carvacrol showed an anti-hyperglycemic effect in diabetic rats, a protective effect against lowering pain threshold, and analgesic activity in rat paws. Carvacrol prevented the oxidant/antioxidant balance from changing in favor of oxidants. The results supported that carvacrol is an agent against alloxan-induced peripheral diabetic neuropathic pain.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2022Amelioration of oxidative damage parameters by carvacrol on methanol-induced liver injury in rats
Gursul, Cebrail; Ozcicek, Adalet; Ozkaraca, Mustafa; Mendil, Ali Sefa; Coban, Taha Abdulkadir; Arslan, Aynur; Ozcicek, Fatih; Suleyman, Halis
The methanol metabolite that causes hepatotoxicity is formic acid, generating reactive oxygen radical formation and cell damage. Carvacrol is an antioxidant monoterpenic phenol produced from Thymus vulgaris. This study aimed to investigate the effects of carvacrol on methanol-induced oxidative liver damage in rats. Eighteen rats were divided into three groups. Methotrexate was administered orally for 7 days to methotrexate+methanol (MTM) and methotrexate+methanol+carvacrol (MMC) groups. Methotrexate was given before methanol to cause methanol poisoning. Distilled water was given to the healthy group (HG) as a solvent. At the end of the 7th day, 20% methanol was administered orally at a dose of 3 g/kg to the MTM and MMC groups. Four hours after methanol administration, 50 mg/kg carvacrol was injected intraperitoneally into the MMC group. Animals were sacrificed 8 h after carvacrol injection. Biochemical markers were studied in the excised liver tissue and blood serum samples, and histopathological evaluations were made. Severe hemorrhage, hydropic degeneration, pycnosis, and mononuclear cell infiltration were observed in the liver of the MTM group. Additionally, the levels of malondialdehyde (MDA), total oxidant status (TOS), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were significantly higher, and total glutathione (tGSH) and total antioxidant status (TAS) were significantly lower in the MTM group compared to HG (P<0.001). Carvacrol prevented the increase in MDA, TOS, ALT and AST levels with methanol and the decrease in tGSH and TAS levels (P<0.001), and alleviated the histopathological damage. Carvacrol may be useful in the treatment of methanol-induced liver damage.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2022C entella asiatica extract protects against cisplatin-induced hepatotoxicity via targeting oxidative stress, inflammation, and apoptosis
Ferah Okkay, Irmak; Okkay, Ufuk; Aydin, Ismail Cagri; Bayram, Cemil; Ertugrul, Muhammed Sait; Mendil, Ali Sefa; Hacimuftuoglu, Ahmet
This study was designed to investigate the protective effects of Centella asiatica (CA) on cisplatin-induced hepatotoxicity and to clarify the underlying mechanism by biochemical, molecular, immunohistochemical, and histopathological analyses. Rats were pre-treated with two doses of CA (100 and 200 mg/kg, p.o.) for 14 consecutive days. Then, on the 15th day, hepatotoxicity was induced by a single cisplatin injection (10 mg/kg i.p.). On the 18th day, the rats were euthanized. CA effectively alleviated cisplatin-induced hepatic injury via reduction in AST, ALT, and ALP enzymes and a decrease in oxidative stress (decreased MDA and ROS, and increased SOD, CAT, and GSH). CA also mitigated the inflammatory damage by the inhibition of TNF-α, IL-1β, and NF-κB. The liver expression of caspase-3 and Bax was downregulated, while Bcl-2 was upregulated. Moreover, immunohistochemical results confirmed the recovery with CA by downregulation of iNOS and 8-OHdG expression. These results showed that with its antioxidant, anti-inflammatory, and anti-apoptotic activities, CA could help alleviate the hepatotoxic effects of cisplatin chemotherapy.
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 Erişim2020Comparative study of the protective effects of adenosine triphosphate and resveratrol against amiodarone-induced potential liver damage and dysfunction in rats
Karadogan, Muhammed Talha; Yavuzer, Bulent; Gursul, Cebrail; Huseynova, Gulbaniz; Yazici, Gulce Naz; Gulaboglu, Mine; Yilmaz, Furkan; Mendil, Ali Sefa; Suleyman, Halis
Background. Amiodarone is the most commonly used class III antiarrhythmic drug with antiarrhythmic and vasodilator properties. Adenosine triphosphate (ATP) serves as a crucial source of intracellular energy, while resveratrol is known for its potent antioxidant activity. Objectives. This study aimed to biochemically, histopathologically and immunohistochemically evaluate the effects of ATP, resveratrol and their combination on potential liver damage and dysfunction induced by amiodarone in rats. Materials and methods. The rats were divided into 6 groups: healthy control (HG), amiodarone alone (ADG), amiodarone + ATP at 2 mg/kg (AAG-2), amiodarone + ATP at 5 mg/kg (AAG-5), resveratrol + amiodarone (RAG), and resveratrol + amiodarone + ATP at 2 mg/kg (RAA-2). Amiodarone (50 mg/kg, orally), ATP (2 mg/kg and 5 mg/kg, intraperitoneally) and resveratrol (25 mg/kg, orally) were administered once daily for 14 days. Following treatment, liver tissues were excised for biochemical analysis. Oxidative stress was assessed by measuring malondialdehyde (MDA) levels, while antioxidant status was evaluated through total glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) levels. To assess liver function, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were measured in serum samples collected from the animals’ tail veins. In addition, liver tissues were subjected to histopathological and immunohistochemical examination to evaluate structural and molecular changes associated with treatment. Results. Amiodarone administration led to a significant increase in oxidative stress markers and a reduction in antioxidant levels in rat liver tissue. Additionally, serum levels of ALT and AST were elevated, indicating liver dysfunction. Histopathological and immunohistochemical analyses revealed severe (grade 3) oxidative damage in the liver tissue. All biochemical parameters in the 5 mg/kg ATP and resveratrol + 2 mg/kg ATP treatment groups were comparable to those observed in the HG group. Histopathological and immunohistochemical evaluations showed a reduction in liver damage severity to grade 2 in the groups treated with ATP (2 mg/kg) and resveratrol alone, and to grade 1 in the groups receiving ATP (5 mg/kg) or the combination of resveratrol + ATP (2 mg/kg). Conclusions. The results of the present study suggest that adjusting the ATP dosage or using a combination of ATP and resveratrol may be effective strategies for minimizing amiodarone-induced liver damage.
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