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- ArticleAçık Erişim2023Effect of pycnogenol on ischemia/reperfusion-induced oxidative and inflammatory damage intheovariesof rats
Dinc, Kemal; Kiremitli, Sevil; Suleyman, Bahadir; Mammadov, Renad; Yavuzer, Bulent; Bulut, Seval; Yazici, Gulce N.; Coban, Taha A.; Altuner, Durdu; Suleyman, Halis
Purpose: To investigate the protective effect of pycnogenol (PYC) against ischemia/reperfusion (I/R) ovarian damage induced by experimental ovarian torsion in rats using biochemical and histopathological methods. Methods: Four groups of rats (n = 6) were randomly assigned and designated as follows - SG: sham group, PCG: pycnogenol (40 mg/kg) group, IRG: ovarian ischemia-reperfusion group, and PIR: pycnogenol (40 mg/kg) + ovarian ischemia-reperfusion group. In IRG and PYC treatment groups, ischemia was induced in the right ovary for two hours with vascular clips. The ovary was reperfused for two hours after ischemia was induced. Then, the levels of malondialdehyde (MDA), total glutathione (tGSH), nuclear factor-kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) in the ovarian tissues of rats were examined. Ovarian tissues were also examined histopathologically and follicle counts were performed. Results: Histopathological examination revealed that the developing follicles in ovary of I/R-induced group showed both morphological and cellular degeneration and vascular pathology. The PYC treatment group showed less ovarian damage, edema and vascular pathology than I/R-induced group (p < 0.05). The MDA, NF-κB, TNF-α and IL-1β levels in I/R-induced group were significantly higher than in SG and tGSH levels were significantly reduced by I/R damage (p < 0.05). Pycnogenol treatment reversed these biochemical indices as well as I/R-induced histopathological changes. Conclusion: Pycnogenol has a protective effect in rat ovaries by alleviating I/R-induced changes in biochemical parameters and histological disruptions. Further studies, including those in humans, to determine the effect of PYC on ovarian injuries would be required.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2022Phoenix Dactylifera L. Tree Fruit Exerts Cardioprotective Effect Against Doxorubicin- Induced Heart Damage in Rats via Inhibition of Oxidative Stress
Coşgun, Muharrem Said; Suleyman, Halis; Celik, Aziz Inan; Çoşkun, Reşit; Dündar, Cihad
Introduction: Phoenix Dactylifera L (PDL) is a fruit containing a rich source of nutrients and bioactive mol- ecules. Doxorubicin is a widely used agent, especially in the treatment of solid cancers. However, cardiotoxicity is one of its most challenging side effects. The present study aimed to investigate the preventive effect of PDL extract against doxorubicin-induced cardiotoxicity. Patients and Methods: A total of 24 albino Wistar rats were divided into four equal groups. Phoenix Dactylifera L (PDLG) and Phoenix Dactylifera L + doxorubicin (PDXG) groups were strictly fed PDL for two weeks. The control group (CG) and the doxorubicin group (DOXG) were fed a standard diet. During this time, 5 mg/kg of doxorubicin was injected intraperitoneally to DOXG and PDXG once a day. Results: Administration of doxorubicin to the DOXG significantly increased tissue oxidative stress parameters and caused the cardiac biomarker troponin-I (TP-I) to be released into the circulation; on the contrary, the levels of potent antioxidants such as total glutathione, superoxide dismutase, and catalase significantly decreased in DOXG compared to the other three groups. However, feeding purely with PDL decreased oxidative stress pa- rameters and TP-I levels in PDXG animals, despite exposure to doxorubicin. Additionally, an excessive decrease of tissue antioxidants was prevented when compared to the DOXG. Histopathological damage signs, such as ne- crosis and hemorrhage, were severe in the DOXG. However, in the PDXG animals, feeding with PDL provided the integrity of the heart tissue structure. Conclusion: PDL was able to improve the cardiotoxic consequences of doxorubicin biochemically and histo- pathologically, possibly due to its antioxidant properties.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2022Effects of Mirtazapine on Liver Ischemia-Reperfusion Injury in Rats
Alemdar, Ali; Yilmaz, Ismayil; Ozcicek, Fatih; Bulut, Seval; Eden, Arif Onur; Gursul, Cebrail; Mendi, Ali Sefa; Kuzucu, Mehmet; Altuner, Durdu; Suleyman, Halis
Background and Objective: Ischemia-reperfusion (I/R) injury begins with tissue oxygen deprivation and continues with oxidative stress and inflammatory response. Mirtazapine is an antidepressant drug with antioxidant and anti-inflammatory properties. The current study was to investigate the effect of mirtazapine against I/R induced liver injury in rats. Materials and Methods: Albino Wistar-type male rats were divided into sham operation (SHAM), I/R (IR) and I/R+mirtazapine administrated (IRM) groups. One hour before anaesthesia, 20 mg kg(-1) mirtazapine was administered to the IRM group of the animals and distilled water was applied to the SHAM and IR groups as a solvent. I/R was achieved by clamping the hepatic artery (except for the SHAM group). Following I/R, all rat groups were killed with high-dose anaesthesia. Malondialdehyde (MDA), total glutathione (tGSH), nuclear factor kappa B (NF-kappa B), interleukin 1 beta (IL-1 beta) and tumour necrosis factor-alpha (TNF-alpha) were determined in liver tissues. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were measured in blood serum. In addition, histopathological examination was performed on liver tissue samples. Results: Mirtazapine prevented increased levels of MDA, NF-kappa B, IL-1 beta, TNF-alpha, ALT and AST in liver tissue with I/R and a decrease in tGSH. Furthermore, mirtazapine has alleviated I/R-associated severe hepatocyte degeneration, necrosis and other structural disorders in the liver. Conclusion: Biochemical and histopathological experimental results suggest that mirtazapine may be useful in the treatment of I/R-induced liver injury.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2022Otoprotective Effect of Nimesulide: Biochemical and Histopathologic Evaluation
Kuduban, Ozan; Suleyman, Zeynep; Gulaboglu, Mine; Yazici, Gulce Naz; Suleyman, Halis
Background and Objective: It is known that nimesulide reduces the toxic effects of Non-Steroidal Anti-Inflammatory Drugs (NSAID), eliminating their inhibitory effects on cyclooxygenase-1 (COX-1) enzyme. COX-1 enzyme inhibition is thought to be responsible for aspirin ototoxicity therefore current study aimed to investigate the effect of nimesulide on aspirin ototoxicity in rats. Materials and Methods: Nimesulide 100 mg kg(-1) orally was administered to the nimesulide+aspirin group (NASA) and the same volume of distilled water as solvent was administered to the aspirin group (ASA) and the healthy (HG) group. Aspirin at a dose of 1000 mg kg(-1) was administered orally to the NASA and ASA group one hour after the administration of nimesulide and solvent. This procedure was repeated once a day for 7 days. Then, the animals were euthanized with a high dose of anaesthesia (50 mg kg(-1) thiopental sodium) and their cochlea and cochlear nerve tissues were removed. Results: Malondialdehyde (MDA) level was significantly higher and total glutathione (tGSH) and cyclooxygenase-1 COX-1 levels were significantly lower in the ASA group in which prominent histopathological damage was found in the cochlea and cochlear nerve, compared to the HG and NASA group. The COX-2 level was found to be almost the same in all the g roups. This indicates that aspirin reduces the COX-1 and tGSH levels and increases the MDA level, causing ototoxicity. Conclusion: Aspirin significantly decreased the COX-1 activity in the cochlea and cochlear nerve tissue, compared to the healthy and nimesulide group. Current study concluded that the co-administration of nimesulide and aspirin will increase the therapeutic effect of aspirin and reduces its side-effects.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2022Effect of Thymoquinone on Diclofenac-Induced Liver Injury
Ekinci, Bilge; Altuner, Durdu; Suleyman, Bahadir; Mammadov, Renad; Bulut, Seval; Suleyman, Zeynep; Gul, Mehmet A.; Ergul, Cetin; Suleyman, Halis
Background and Objective: Thymoquinone (TQ) is an active phenolic compound obtained from Nigella sativa L. It has anti-inflammatory and antioxidant activity by inhibiting the overproduction of certain inflammatory molecules and lipid peroxidation. TQ also has a hepatoprotective effect. This study, it was aimed to biochemically investigate the effect of TQ on diclofenac (DC)-induced liver damage in rats. Materials and Methods: The animals were divided into healthy control (HG), only diclofenac (DG), only thymoquinone (TQG) and diclofenac+thymoquinone (DTQG) groups. The DC was injected intraperitoneally at a dose of 25 mg kg(-1). The TQ was administered orally to the stomach at a dose of 20 mg kg(-1). This procedure was repeated once a day for 7 days. Results: Biochemical test results showed that TQ significantly prevented the increase in oxidant parameters and the decrease in antioxidants in liver tissue, which is formed by DC. Also, DC and TQ inhibited the increase of proinflammatory cytokines in liver tissue. The TQ also prevented the decrease of COX-1 activity by DC and increased the inhibition of COX-2. The TQ also significantly suppressed the elevation of liver function markers such as Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) with DC. Conclusion: These findings indicated that the hepatotoxic effect of DC was due to oxidative stress and inhibition of cytoprotective structural COX-1 enzyme. It suggested that TQ may be useful in the treatment of DC-related liver injury.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2022Is Benidipine Effective in Preventing Gastric Ischemia/Reperfusion Injury?
Bilici, Sami; Tas, Hakan Gokalp; Mamedov, Renad; Suleyman, Bahadir; Kuyrukluyi, Ufuk; Yavuzer, Bulent; Bulut, Seval; Coban, Abdulkadir; Suleyman, Halis
Background and Objective: The preventive effect of benidipine on organs and tissues against oxidative and proinflammatory cytokine damage, whose production is elevated by I/R, has been demonstrated. The current study noted that benidipine affects the biochemical and histopathological effects of I/R therapy on gastric injury in rats. Materials and Methods: A total of 18 rats were divided into either a Sham operation group (SG), gastric ischemia/reperfusion (GIR) group or benidipine+gastric ischemia/reperfusion (BGIR) groups. Biochemical measures and histological exams were done in all three groups after I/R intervention. Results: The MDA, TNF-alpha, IL-1 beta and COX2 levels were significantly higher (p<0.001) in GIR compared to SG and BGIR, although tGSH and COX1 were significantly lower (p<0.001). The SG group was histopathologically normal. The surface epithelium broke off in spots, causing mild degeneration, the gland recesses were decreased, the gland neck areas were wide, the base areas were significantly oedematous and the blood capillaries showed moderate dilatation and congestion in the GIR group. Infiltration of polymorphonuclear cells was seen in the connective tissue surrounding the arteries and close to the gland bases. The BGIR group's histopathological results were not normal, although they were milder than the GIR group's. Conclusion: The results discovered that benidipine shifted the oxidant/antioxidant balance in I/R damage in favour of antioxidants, as well as the COX-1/COX-2 equilibrium in favour of COX-2, which is cytoprotective. It appears that administering benidipine for antioxidant and cytoprotective purposes before surgical operations that are likely to cause I/R damage may be advantageous.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2022The Effect of Anakinra on Acrylamide-induced Peripheral Neuropathy and Neuropathic Pain in Rats
Ersoy, Alevtina; Tanoglu, Ceyda; Yazici, Gulce Naz; Coban, Taha Abdulkadir; Mammadov, Renad; Suleyman, Halis
Acrylamide is a neurotoxic compound. Moreover, anakinra is an interleukin-1 (IL-1) receptor antagonist used in rheumatoid arthritis treatment. This study investigated the effect of anakinra on acrylamide-related neuropathy and neuropathic pain. Acrylamide exposure caused a significant decrease in the pain threshold; an increase in malondialdehyde (MDA), tumor necrosis factor -alpha (TNF-alpha), and interleukin-1 beta (IL-113) levels; and a decrease in total glutathione (tGSH) values in the sciatic nerve. This indicates hyperalgesia presence, oxidative stress, and peripheral nerve tissue inflammation. Anakinra treatment significantly reduced the MDA, IL-113, and TNF-alpha levels, and increased the pain threshold and mean tGSH values. The analgesic effect of anakinra was 67.9% at the first hour, increasing to 74.9% and 76.7% at the second and third hours, respectively. The group receiving acrylamide exhibited histopathological changes (e.g., swollen and degenerated axons, hypertrophic and hyperplasic Schwann cells, and congested vessels). The use of anakinra significantly improved these morphological changes. Anakinra is concluded to reduce neuropathic pain and prevent neurotoxic effect of acrylamide on peripheral nerves due to its analgesic, antioxidant, and anti-inflammatory properties.
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 thymoquinone on cyclophosphamide-induced oxidative and inflammatory ovarian damage in rat
Colluoglu, Cagdas; Balci, Serdar; Gundogdu, Betul; Coban, Taha Abdulkadir; Bulut, Seval; Suleyman, Halis
This study intends to investigate the effect of thymoquinone against possible ovarian damage and infertility caused by cyclophosphamide in female rats. The rats in the experiment (n=36) were separated into three groups; cyclo-phosphamide administered, thymoquinone plus cyclophosphamide administered and healthy control. At the end of 30 days of administration, 6 rats from each group were killed and the biochemical and histopathological examina-tions were performed on the ovarian tissues. The remaining animals were kept in the same cage with mature male rats for two months. Infertility developed in 83% of cyclophosphamide group animals. Thymoquinone atte-nuated cyclophosphamide-related oxidative and inflammatory ovarian damage and reduced the development of infertility. The outcomes suggest that thymoquinone may be useful in treating infertility due to oxidative and inflammatory ovarian damage.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2022The effects of thiamine pyrophosphate on propofol-induced oxidative liver injury and effect on dysfunction
Delen, Leman Acun; Dişli, Zeliha Korkmaz; Taş, Hakan G.; Kuyrukluyildiz, Ufuk; Yazici, Gulce N.; Süleyman, Bahadir; Kuzucu, Mehmet; Gürsu, Cebrail; Suleyman, Halis
Propofol may cause an increase in reactive oxygen species in the body. In this study, we tested the effect of antioxidant thiamine pyrophosphate (TPP) on propofol-induced liver damage. The eighteen rats were split into three groups: HG, healthy; PP, propofol-treated (50 mg/kg) and PT, treated with propofol (50 mg/kg) and TPP (25 mg/kg). Total glutathione (tGSH), total oxidant (TOS), and total antioxidant (TAS) levels were tested together with aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and malondialdehyde (MDA). Histopathological examination of the tissues was performed. We have found that levels of MDA, TOS, ALT, AST, and LDH were all higher in PP group than in HG and PT groups (p < 0.05). In PP group, the TAS and tGSH levels were statistically substantially lower. The PT for oxidants levels showed a statistically significant reduction. In PT group, the levels of antioxidants were found to be considerably higher. The epitheliums, glands, and vascular structures of the PTs were histologically close to normal. By boosting antioxidants, TPP may help to reduce propofol-induced liver damage.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2022The effect of carvacrol on oxido-inflammatory ovarian injury and infertility induced by ischemia-reperfusion in rats
Sahin, Nurullah; Delibas, Ilhan Bahri; Isaoglu, Unal; Suleyman, Bahadir; Yazici, Gulce Naz; Coban, Taha Abdulkadir; Uzel, Kemine; Suleyman, Halis; Arslan, Veysel
Background: Increased oxidants and proinflammatory cytokines play a role in the pathogenesis of ovarian ischemia-reperfusion (OIR) injury and related infertility. Carvacrol has antioxidant, antibacterial and anti-inflammatory properties. Methods: Protective effect of carvacrol against ischemia-reperfusion (IR)-related ovarian damage and infertility was investigated. IR process were applied to the ovaries of rats, which were divided into the following groups (n = 12): OIR, IR +50 mg/kg carvacrol (IRC-50), IR +100 mg/kg carvacrol (IRC-100) and sham group (SG). After the reperfusion process, six rats from each group were killed and the removed ovaries were examined biochemically and histopathologically. The remaining animals were kept two months with mature male rats to reproduce. Results: At a dose of 50 mg/kg, carvacrol suppressed the oxidant parameter increase and antioxidant decrease caused by IR in ovarian tissue. At a dose of 100 mg/kg, carvacrol antagonized both oxidant and proinflammatory cytokine increase and antioxidant decrease. Histopathologically, severe degeneration of follicles in the ovaries of the OIR group, necrotic cell accumulations, hemorrhage in the corpus luteum, edema in the interstitial tissue, polymorphous nuclear leukocyte (PNL) infiltration, and congestion and dilation of blood vessels were detected. Inflammatory symptoms such as edema in the ovarian tissue, congested dilated blood vessels and PNL infiltration were observed at a dose of 50 mg/kg of carvacrol, but these histopathological findings were not observed at a dose of 100 mg/kg. Conclusion: A dose of 100 mg/kg carvacrol, which eliminated inflammatory damage, significantly prevented the development of IR-induced infertility. Carvacrol may be beneficial in the treatment of IR-related ovarian damage and infertility. Copyright:
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2022EFFECT OF NIMESULIDE AGAINST INDOMETHACININDUCED OXIDATIVE LIVER DAMAGE IN RATS
Yilmaz, Canan T.U.Z.; Suleyman, Bahadir; Mammadov, Renad; Ozcicek, Adalet; Bulut, Seval; Yazici, Gulce N.A.Z.; Gulapoglu, Mine; Suleyman, Halis
Indomethacin is used in the treatment of ankylosing spondylitis, osteoarthritis, tendinitis, and other inflammations. However, it has been reported indomethacin has nephrotoxic, gastrotoxic, and hepatotoxic effects. The aim of this study is to investigate the effect of nimesulide on indomethacin-induced liver damage in rats biochemically and histopathologically. Experimental animals (21 rats) were divided into 3 groups: the healthy (HG) group receiving distilled water as a solvent, the 25 mg/kg indomethacin administered (IDO) group, and the 50 mg/kg nimesulide + 25 mg/kg indomethacin administered (NIDO) group. Malondialdehyde (MDA), total glutathione (GSH) levels and cyclooxygenase-1 (COX-1), cyclooxygenase (COX-2) enzyme activities were determined from liver tissues. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were also measured in serum. The data obtained in the IDO group were compared with the data obtained from the NIDO and MDA and decreased tGSH levels with indomethacin HG groups. Increased application in liver tissue approached the HG group with nimesulide application, and the difference was found to be insignificant. Nimesulide prevented the decrease in COX-1 and COX-2 levels observed with indomethacin administration. Again, the increase in ALT and AST levels, which increased with indomethacin administration, was prevented by nimesulide. As a result of the histopathological evaluation, it was observed that nimesulide reduced the damage caused by indomethacin. Nimesulide at 50 mg/kg prevented oxidative liver damage induced with indomethacin at 25 mg/kg. Our results suggest that nimesulide may be useful in the treatment of hepatotoxicity and COX-1 inhibition side effects without suppressing analgesic and anti-inflammatory activity due to indomethacin use.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2022Effects of ketamine, thiopental and their combination on the rat liver: A biochemical evaluation
Bedir, Zehra; Ozkaloglu Erdem, Kezban Tuna; Ates, Irem; Olmezturk Karakurt, Tulay Ceren; Gursul, Cebrail; Onk, Didem; Kurt, Nezahat; Suleyman, Zeynep; Suleyman, Halis
Background. In the literature, it has been suggested that ketamine-related oxidative organ damage results from increased blood adrenaline level, and thiopental-related oxidative damage is caused by decreased adrenaline level, suggesting that ketamine-thiopental combination (KT) may be beneficial in reducing the hepatotoxic effect of ketamine. Objectives. To biochemically investigate the effects of ketamine, thiopental and KT on the liver in rats. Materials and methods. Male albino Wistar type rats received intraperitoneally (ip.) 30 mg/kg ketamine in the ketamine alone (KG) group (n = 6), 15 mg/kg thiopental in the thiopental alone (TG) group (n = 6), and 30 mg/kg ketamine + 15 mg/kg thiopental in the ketamine+thiopental (KTG) group (n = 6). The same volume of distilled water as solvent was given to the healthy (HG) animal group. This procedure was repeated once daily for 30 days. At the end of this period, the animals were killed by decapitation and their livers were removed. In liver tissue, malondialdehyde (MDA), total glutathione (tGSH), total oxidant status (TOS), total antioxidant status (TAS), tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), and interleukin-6 (IL-6) levels were measured. The IL-1β, IL-6, TNF-α, adrenalin (ADR), noradrenalin (NDR), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels were determined in blood samples taken from the tail veins. Results. In the group treated with ketamine and thiopental alone, MDA, TOS, IL-1β, IL-6, TNF-α, ADR, NDR, ALT, and AST levels were found to be high, and those of tGSH and TAS to be low. However, there was no significant change in the levels of these parameters in the KTG. Conclusions. These results indicate that oxidative stress and inflammation developed in the liver tissue of the group that used ketamine and thiopental alone, suggesting that the KT form may be safer in terms of toxicity in the clinical usage.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2022The protective effect of carvacrol on bevacizumab-related skin injury in rats: a biochemical and histopathological evaluation
Gore Karaali, Muge; Karaali, Soner; Demir, Damla; Yazıcı, Gulce Naz; Coban, Abdulkadir; Mammadov, Renad; Suleyman, Bahadır; Suleyman, Halis
Purpose: Bevacizumab is a recombinant humanized monoclonal antibody that specifically binds to vascular endothelial growth factor (VEGF). Cutaneous side effects of bevacizumab are seen with substantial frequency and may require the interruption of the treatment. The aim of the study was to conduct a biochemical and histopathological investigation of the effects of carvacrol against the possible oxidative skin damage caused by bevacizumab in rats. Materials and methods: A total of 18 adult male Wistar albino rats were randomly assigned to three groups as healthy (H group; n = 6), bevacizumab alone (B group; n = 6), and carvacrol + bevacizumab (CB group; n = 6). Carvacrol was injected intraperitoneally (IP) at a dose of 50 mg/kg in the CB group. Sterile salt solution (0.9% NaCl) was used as a solvent for the H and B groups. One hour after the administration of carvacrol and solvent, bevacizumab at a dose of 10 mg/kg IP was administered to the CB and B groups. Bevacizumab was given once daily for a total of two doses, 15 days apart. Carvacrol was administered once daily for one month. After that period, all animals were sacrificed and their skin tissues removed. Malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GPO), catalase (CAT), superoxide dismutase (SOD), total oxidant status (TOS), and total antioxidant status (TAS) levels in rats’ skin tissues were biochemically evaluated. The parameters were measured with spectrophotometric method by using a microplate reader (BioTek, Winooski, VT, USA). The skin tissues were also examined histopathologically by the pathologist (blind) for the study groups. Results: The MDA and TOS levels of the H and CB groups were significantly lower than the B group (p < 0.05). The mean scores of the other biochemical levels (GSH, GPO, CAT, SOD, TAS) in the H group were significantly higher than in the B and CB groups. Pathological examination of H group was normal. In B group epidermal atrophy, abnormal keratin accumulation, degenerated hair follicles, edoema and inflammatory cells accumulation in the dermis were observed. In the CB group, these findings were significantly improved. Conclusion: The positive effect of carvacrol against possible local oxidative skin damage due to bevacizumab in rats was demonstrated. In addition, more detailed studies are required to clarify the mechanism of the protective effect of carvacrol against bevacizumab-induced skin toxicity. The effect should be evaluated through further human studies, as well as studies using different doses of carvacrol.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2022The Effect of Thiamine Pyrophosphate and Tocilizumab Alone and in Combination upon Ethanol-Induced Peripheral Neuropathy and Neuropathic Pain in Rats
Ekinci, Bilge; Suleyman, Bahadir; Mammadov, Renad; Cankaya, Murat; Yazici, Gulce Naz; Suleyman, Zeynep; Dal, Cagatay Nusret; Ergul, Emine Esra; Onk, Didem; Suleyman, Halis
The aim of the study to determine the effects of thiamine pyrophosphate (TPP) and tocilizumab (TCZ) either alone or in combination on ethanol-induced neuropathic pain and peripheral neuropathy in rat nerve tissues, biochemically and histopathologically. Albino Wistar male rats were divided into five groups as the healthy (HG), ethanol alone (EtOH), TPP + ethanol (TPE), TCZ + ethanol (TCE), and TPP + TCZ + ethanol (TPTE) groups. TPE (n = 6), TCE (n = 6) and TPTE (n = 6) groups were injected with 20 mg/kg TPP, 8 mg/kg TCZ, and 20 mg/kg TPP+8 mg/kg TCZ intraperitoneally (respectively). Distilled water were given the HG (n = 6) and EtOH (n = 6) groups. One hour after the drugs and distilled water were administered, 35% ethanol was administered orally by lavage at a 5 g/kg dose to the TPE, TCE, TPTE, and EtOH groups. Paw pain thresholds of animals were measured using Basile Algesimeter. TPTE, which suppressed the decrease of the pain threshold with ethanol more significantly than TPP and TCZ. The best inhibitor of MDA increase and inhibit the reduction of tGSH by etanol was listed as TPTE > TPE > TCZ. The potency of suppressing the increase in cytokine production with ethanol was listed as TPTE > TCE > TPE. In conclusion, the results indicate that TPP+TCZ may be more beneficial than TPP and TCZ alone in treating ethanol-related neuro-pathic pain.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2022Effect of Thymoquinone on Everolimus-Induced Oral Toxicity in Rats. A Macroscobic and Biochemical Evaluation
Dilber, Muhammet; Salcan, Ismail; Suleyman, Bahadir; Mammadov, Renad; Altuner, Durdu; Aggul, Ahmet G.; Esen, Mehtap; Bulut, Seval; Suleyman, Zeynep; Yavuzer, Bulent
Everolimus is a drug within the class of mammalian target of rapamycin inhibitors (mTOR). The most widespread side effect observed is oral mucositis.Thymoquinone is a phenolic compound obtained antioxidant and anti-inflammatory activities. The aim of this study is to investigate the protective effect of thymoquinone against oral toxicity that may develop due to everolimus in rats. Albino Wistar male rats were divided into healthy(HG), everolimus(EVR), thymoquinone(TQG) and thymoquinone+everolimus(TQE) groups. Thymoquinone (20 mg/kg) was administered to the TQG and TQE groups orally. One h after, TQE and EVR groups were given everolimus to (2 mg/kg) the stomach. This procedure was repeated once a day for four weeks. After 4 weeks, animals were euthanized, tongue and cheek tissues were examined biochemically and histopathologically. Thymoquinone prevented the increase of oxidant and proinflammatory cytokines and the decrease of antioxidants in the tongue and cheek tissues of animals, and also reduced the histopathological damage.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2022The Molecular Mechanism of the Effect of Carvacrol on Desflurane Inhalation-Induced Liver Damage in Rats
Disli, Zeliha Korkmaz; Acun Delen, Leman; Tas, Hakan Gokalp; Kuyrukluyildiz, Ufuk; Disli, Olcay Murat; Yazici, Gulce Naz; Coban, Abdulkadir; Suleyman, Halis
The metabolite of desflurane has been linked to hepatotoxicity. Carvacrol possesses antioxidant, antibacterial, antifungal, anticancer, anti-inflammatory, and spasmolytic properties, according to research. Our goal is to demonstrate that carvacrol protects rats’ livers against repeated doses of desflurane. Healthy (HG), desflurane (DS), and carvacrol + desflurane treatment (CDS) groups were formed from 18 albino male Wistar rats. A single dosage of carvacrol and 6% desflurane was given for 2 h on the 0th and 8th days. In the CDS group, the ALT and AST, MDA, TOS, NF-xB, TNF-α IL1 β levels were lower compared to the DS group (p < 0.001). The tGSH,TAS levels were found to be higher in the CDS group compared to the DS group (p < 0.001). It was determined that the mean degeneration level, Kupffer cell activation and PMNL infiltration were found to be lower compared to the DS group (p < 0.05).We confirmed that carvacol can be used in the treatment of desflurane-related liver injury.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2022The effect of taxifolin on experimental testicular ischaemia reperfusion injury in rats. A biochemical and histopathological analysis; [Efecto de la taxifolina en la lesión experimental testicular por reperfusión-isquemia en ratas. Análisis bioquímico e histopatológico]
Bedir, Fevzi; Kocaturk, Huseyin; Ozgeris, Fatma Betul; Yazici, Gulce Naz; Suleyman, Zeynep; Suleyman, Halis
Objectives: The aim of the study is to investigate the protective effect of taxifolin (3,5,7,3,4-pentahydroxy flavanone), a strong antioxidant, against testicular I/R injury in rats biochemically and histopathologically. Materials and methods: 50 mg/kg taxifolin was administered to taxifolin + testicular torsion–detorsion (TTTD, n-10) group of Albino Wistar male rats by oral gavage. Distilled water .5 ml as a solvent was administered to testicular torsion–detorsion (TTD, n-10) and Healthy Control (SG, n-10) groups using the same method. An hour after the administration of taxifolin and distilled water, anaesthesia (ketamine 60 mg/kg) was administered to all animal groups. TTD and TTTD group animals were subjected to testicular torsion at 720 degrees for four hours during anaesthesia. At the end of this period, testicular detorsion was applied and perfusion was allowed for four hours. Sham operation was applied to SG group. Results: Our biochemical experiment results showed that the amount of malondialdehyde (MDA) in testicular tissue of TTD group presented a significant increase compared to SG and TTTD groups whereas total glutathione (tGSH) and superoxide dismutase (SOD) levels decreased. In addition, while TTD group presented severe histopathological damage in germinal epithelium cell and seminiferous tubule, mild damage was observed in TTTD group. Conclusions: The results of our experiment indicate that taxifolin could be useful in the treatment of testicular I/R damage.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2022Beneficial interaction of pycnogenol with indomethacin in rats
Ekinci, Bilge; Suleyman, Bahadir; Mammadov, Renad; Bulut, Seval; Ozcicek, Adalet; Ergul, Cetin; Gulaboglu, Mine; Hayme, Serhat; Suleyman, Halis
Cyclooxygenase 2 (COX-2) is responsible for the therapeutic effects of indomethacin, while inhibition of the COX-1 enzyme and oxidative stress are responsible for its gastro-toxic effects. It has been reported that pycnogenol increases the expression of COX-1, suppresses the expression rate of COX-2 and oxidative stress. Our aim in this study is to investigate the antiinflammatory activities of indomethacin, pycnogenol, and their combination (PI) in rats and to examine their effects on stomach tissue. In the study, anti-inflammatory activity was investigated in carrageenan-induced inflammatory paw edema in albino Wistar male rats. Effects on stomach tissue were performed by applying the previous method. PI, indomethacin and pycnogenol were the best suppressors of carrageenan inflammation and oxidative stress in paw tissue, respectively. While the groups with the lowest COX-1 activity in paw tissue were IC, PIC and PC, respectively, PIC, IC and PC were the ones that best inhibited the increase in COX-2 activity. Pycnogenol inhibited the increase of malondialdehyde, the decrease of total glutathione and COX-1 in the stomach, and significantly suppressed the formation of indomethacin ulcers. Our experimental results showed that pycnogenol reduced the toxic effect of indomethacin on the stomach and increased anti-inflammatory activity. This beneficial interaction of pycnogenol and indomethacin suggests that PI will provide superior success in the treatment of inflammatory diseases.
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.
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