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- ArticleAçık Erişim2020Biochemical Investigation of the Protective Effect of Thiamine Pyrophosphate on Methotrexate-Induced Gastrotoxicity in Rats
Cinar, Irfan; Gulapoglu, Mine; Suleyman, Halis
Aim: The aim of the study is to investigate the protective effect of thiamine pyrophosphate on methotrexate- induced gastrotoxicity biochemically in rats and to compare it with thiamine. Methods: Rats were divided into four groups as sham (SG), thiamine+ methotrexate (TAMTX), thiamine pyrophosphate +methotrexate (TPMTX) and Methotrexate (MTX) groups. 5 mg/kg methotrexate was administrated to 24 hr-fasted rat groups by oral gastric tube except sham rats. 20 mg/kg thiamine was injected to TAMTX group and 20 mg/kg thiamine pyrophosphate was injected to TPMTX group i.p. 5 min before the methotrexate administration. Equal amount distilled water was injected i.p. to SG and MTX groups. 6 hr after the methotrexate administration, the rats were sacrificed with high dose thiopental anesthesia (50 mg/kg). The stomachs of the rats were extracted and MDA, MPO, GSH and SOD analyzes were performed. Results: Biochemical results were evaluated by comparing among groups. While tGSH and MDA levels and MPO and SOD activities were 4.2 +/- 0.6, 10.0 +/- 0.9, 7.4 +/- 0.8, 5.2 +/- 0.9 mu mol/g in MTX group, these parameters were 11.0 +/- 1.0, 3.4 +/- 0.4, 3.3 +/- 0.5, 13.2 +/- 1.1 mu mol/g in SG group in the gastric tissue. These parameters were measured as 4.8 +/- 0.8, 8.7 +/- 0.8, 5.9 +/- 0.5, 6.1 +/- 0.8 mu mol/g in TAMTX group and 10.8 +/- 0.8, 4.0 +/- 0.5, 3.6 +/- 0.4, 10.5 +/- 0.9 mu mol/g in TPMTX group. Conclusion: The results showed that thiamine pyrophosphate prevented methotrexate induced oxidative damage in the gastric tissue, but thiamine could not prevent.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2020The effect of lutein on paclitaxel-induced neuropathy and neuropathic pain in rats
Yasar, Hasan; Ersoy, Alevtina; Yazici, Gulce Naz; Suleyman, Halis; Özgeris, Fatma Betul; Arslan, Yusuf Kemal; Sunar, Mukadder
Background: Paclitaxel is a drug used to treat cancer, but it causes neuropathic pain and peripheral neuropathy. One of the causes of these effects of paclitaxel on nerve tissue is oxidative damage. Lutein has antioxidant effects. In this study, it was investigated the influence of lutein whether decrease oxidative damage of paclitaxel on nerve tissue or not. Methods: Pain threshold (PT) in paw of paclitaxel-only group (PC), paclitaxel+lutein group (PL), and control group (CG) rats were measured using a Basile algesimeter. The sciatic nerve tissue of experimental animals was used to conduct biochemical analyses. Analyses of malondialdehyde (MAD), total glutathione (GT), myeloperoxidase (MP), interleukin 1 beta (IL-1 beta) were performed. Histopathologic examination was performed in all groups. The CG and the other groups were compared. Results: PT was lowest in the PC group. However considerable increase in pain threshold in paw was observed in the PL group with respect to the PC group. As a result, the usage of lutein increased PT in paw. The PC group had signs of oxidative damage. With the use of lutein, paclitaxel was prevented from causing oxidative damage. Histopathological examination revealed that paclitaxel caused damage to myelin sheath and axon of sciatic nerve tissue. However, lutein was found to prevent this damage to the myelin sheath and axon. Paclitaxel causes neuropathic pain and peripheral neuropathy. One of the causes is the oxidative damage of paclitaxel in nerve tissue. Conclusion: Lutein, which has an antioxidant effect, prevents the damage of paclitaxel on nerve tissue.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2020Effect of Taxifolin on Cobalt-induced Ototoxicity in Rats: A Biochemical and Histopathological Study
Salcan, Ismail; Dilber, Muhammet; Bayram, Rana; Suleyman, Esma; Erhan, Ertugrul; Yi, Sevil Karahan; Yazici, Gulce Naz; Coban, Abdulkadir; Suleyman, Halis
Background and Objective: Cobalt is a metal with a significant hazard profile, used widely in many industries. The reported hazards of Cobalt include effects on the heart, thyroid, immune system, vision and hearing organs as a result of exposure to high doses. This study aimed to evaluate the biochemical and histopathological effect of taxifolin on Co-induced ototoxicity in rats. Materials and Methods: Distilled water was administered to the Healthy Group (HG) and cobalt-only (Co) groups of animals and a third group was orally given 50 mg kg(-1) Taxifolin+Cobalt (TCo) by gavage. After 1 hr, 150 mg kg(-1) CoCl2 was administered orally to the stomach by gavage to the animals in the TCo and the Co groups. This procedure was repeated once a day for seven days. Results: Malondialdehyde (MDA), Nuclear Factor-Kappa B (NF-kappa B), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) levels were significantly higher than the HG and TCo groups and the cochlear nerve tissue was damaged by significant histopathological damage in the Co group with low total glutathione (tGSH) levels. In the TCo group, biochemical and histopathological findings were found to be close to the HG group. Conclusion: This study revealed the role of oxidative stress and proinflammatory cytokines in the pathogenesis of Co ototoxicity. Our results suggest that taxifolin may be useful in the treatment of Co-related ototoxicity.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2020The effect of rutin on experimental traumatic brain injury and edema in rats
Yuceli, Sahin; Yazici, Gulce Naz; Mammadov, Renad; Suleyman, Halis; Kaya, Mustafa; Ozdogan, Selcuk
Background/Aim: The aim of the study was to evaluate the effect of rutin, which is a vitamin P1 flavonoid with anti-inflammatory and anti-edema effects, on traumatic brain injury (TBI) and edema in rats. Materials and Methods: Rats were divided into 3 groups as sham group without brain trauma (SG), brain trauma without medication (BT) group and Rutin treated brain trauma (RBT) group. Fifty mg/kg rutin was administered to the RBT group once a day for three days. On the fourth day, rats were sacrificed. Extracted brain tissues were examined biochemically and histopathologically. Results: We found that the levels of malondialdehyde, nuclear factorkappa B and tumor necrosis factor-alpha decreased, and those of total glutathione increased significantly. Furthermore, rutin administration reduced pyramidal neuron degeneration and poly-morpho-nuclear-leucocyte accumulation due to trauma in brain tissue, while eliminating edema. Conclusion: Rutin might be effective in the treatment of TBI and TBI-related brain edema.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2020The effect of desloratadine on ischemia reperfusion induced oxidative and inflammatory renal injury in rats
Kocaturk, Huseyin; Bedir, Fevzi; Altay, Mehmet Sefa; Bakan, Ebubekir; Suleyman, Bahadir; Yazici, Gulce Naz; Sunar, Mukadder; Suleyman, Zeynep; Suleyman, Halis
Purpose: To examine the effect of desloratadine on kidney ischemia-reperfusion (I/R) injury in albino Wistar male rats using biochemical and histopathological methods. Methods: The treated with ischemia–reperfusion + 5 mg/kg desloratadine (IRD) group (n–6) was given 5 mg/kg desloratadine by gavage orally, and applied renal ischemia-reperfusion (BIR) group (n–6) and control (SG) group undergoing Sham operation (n–6) rats were given distilled water as solvent one hour before ketamine anesthesia. During the anesthesia period, ischemia was induced for 2 h unilaterally in the left kidney of all rats followed by reperfusion for 6 h. The kidneys of the SG group had sham operation without any intervention. Results: Our biochemical test results showed that malondialdehyde (MDA), nuclear factor kappa (NF-κB), tumor necrosis factor alpha (TNF-α), interleukin one beta (IL-1β), creatinine, and blood urea nitrogen (BUN) levels were significantly increased in the BIR group compared to the healthy control and IRD groups treated with desloratadine. Histopathological results were revealed tubular dilatation, tubular necrosis, loss of brushy margins, cast formation, and apoptotic bodies in tubular epithelial cells in the BIR group. There were no histopathological findings except for the swelling of tubule epithelial cells and the accumulation of proteinous material in some tubule lumens in renal tissue of desloratadine-treated rats. Conclusions: Experimental results suggested that desloratadine may be useful in the treatment of renal I/R injury.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2020The effect of Liv-52 on liver ischemia reperfusion damage in rats
Cimen, Orhan; Eken, Hüseyin; Keskin Cimen, Ferda; Cekic, Arif Burak; Kurt, Nezahat; Ozbek Bilgin, Asli; Suleyman, Bahadir; Suleyman, Halis; Mammadov, Renad; Pehlivanoglu, Kamil
Background: Liver ischemia reperfusion (I/R) damage which is frequently seen in clinical hepatobiliary surgeries has no effective treatment for it. Liv-52, known to have hepatoprotective effects, is a natural antioxidant drug licensed by the Ministry of Health of India. The aim of our study is to investigate the effect of Liv-52 on liver damage induced by I/R in rats. Methods: Albino Wistar male rats were divided into three groups; liver I/R (IR), 20 mg/kg Liv-52 + liver ischemia reperfusion (LIR) and sham operation applied to control group (HG). Liv-52 was administered to the LIR group (n = 6) 1 h prior to I/R application and distilled water was given orally to IR (n = 6) and HG (n = 6) groups as a solvent. Ischemia was determined as 1 h, and reperfusion was identified as 6 h in animals. Results: Increased levels of alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase, malondialdehyde, myeloperoxidase, and decreased levels of superoxide dismutase, and glutathione related enzymes caused by I/R application have been converged to healthy group level with Liv-52 treatment and the damage in liver tissue has been improved histopathologically. Conclusions: Liv-52 may be beneficial for preventing liver I/R damage in pre-surgery application.
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.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2020Effects of anakinra on the small intestine mucositis induced by methotrexate in rats
Ozcicek, Fatih; Kara, Ali Veysel; Akbas, Emin Murat; Kurt, Nezahat; Yazici, Gulce Naz; Cankaya, Murat; Mammadov, Renad; Ozcicek, Adalet; Suleyman, Halis
Intestinal mucositis is an important problem in the patients receiving cancer treatment. We aimed to investigate the effect of anakinra, which is a well known anti-oxidant and anti-inflammatory agent, on methotrexate-induced small intestine mucositis in rats. Forty rats were divided into 4 groups with 10 in each group. The healthy group (HG) and the methotrexate group (MTXG) were given distilled water, while the methotrexate + anakinra 50 (MTX+ANA50) and the methotrexate + anakinra 100 (MTX+ANA100) groups were intraperitoneally administered 50 and 100 mg/kg of anakinra. After one hour, the MTXG, MTX+ANA50 and MTX+ANA100 groups were given oral methotrexate at a dose of 5 mg/kg. This procedure was repeated once a day for 7 days. After the rats had been sacrificed, the small intestine tissue of rats were removed for the assesment of biochemical markers, histopathological evaluation and gene expression analyze. Statistical analyses of the data were performed using one-way ANOVA. Malondialdehyde (MDA), myeloperoxidase (MPO) and interleukin-6 (IL-6) levels were significantly higher, whereas total glutathione (tGSH) levels were significantly lower in MTXG (P<0.001) compared to other groups. MTX also increased IL-1β and TNF-α gene expression levels in MTXG (P<0.001). Inflammatory cell infiltration and damage to the villus were observed histopathologically in the MTXG group, whereas only mild inflammation was seen in the MTX+ANA100 group. A dose of 100 mg/kg of anakinra prevented the increase of the biochemical markers and gene expression levels better than a dose of 50 mg/kg. Intestinal mucositis caused by MTX may be preventible by co-administered anakinra.
RDL Kalıcı Kaydıİncele - ArticleYayıncıda açık erişim2020The protective effect of lercanidipine on indomethacin-induced gastric ulcers in rats
Altuner, Durdu; Kaya, Tuğba; Suleyman, Halis
Nonsteroidal anti-inflammatory drugs (NSAID) are among the aggressive factors causing gastric ulcer. They cause oxidative damage in the gastric tissue and lead to intracellular calcium deposition. Lercanidipine is a calcium channel blocker derived from the third generation dihydropyridine. The aim of this study is to analyse the effect of lercanidipine on indomethacin-induced gastric ulcers. A total of 24 albino Wistar male rats were divided into four groups; those who received indomethacin 25 mg/kg (IND), 5 mg mg/kg lercanidipine +25 mg/kg indomethacin (LC-5), 10 mg/kg lercanidipine+25mg/kg indomethacin (LC-10) and healthy rats who received 0.5 mL distilled water. Six hours after the application of indomethacin, the animals were sacrificed by high dose thiopental sodium. The stomachs of the animals were excised to perform a macroscopic analysis and the ulcerous region was measured on millimeter paper. All the stomachs were subjected to a biochemical analysis. Macroscopic analysis revealed hyperaemia on the gastric surface of the indomethacin group. Ulcerous tissues formed by oval, circular or irregular mucosal defects in varying diameters and depths were observed on the whole surface of the stomach. Hyperaemia was lower and ulcerous region was smaller in groups LC-5 and LC-10 compared to IND group. Malondialdehyde and myeloperoxidase levels were significantly lower and total glutathione and cyclooxygenase-1 activity were higher in groups LC-5 and LC-10. Lercanidipine did not change the cyclooxygenase-2 activity. Lercanidipine in doses 10 mg/kg is more effective compared to 5 mg/kg. Lercanidipinine can be useful in the treatment of NSAID-induced gastric damage.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2020The effect of anakinra on paclitaxel induced auditory nerve damage in rats
Bayram, Rana; Erhan, Ertugrul; Seckin, Ender; Salcan, Ismail; Mammadov, Renad; Kurt, Nezahat; Suleyman, Halis
In this study, we have examined the protective and proinflammatory effects of anakinra against paclitaxel-associated oxidative auditory nerve damage induced by paclitaxel in rats. Experimental animals were allocated into three groups: Paclitaxel administered controls, paclitaxel + anakinra administered group, and untreated health controls. At the end of this period, animals were sacrificed by high dose thiopental (50 mg/kg) anesthesia and auditory nerves were removed. Then, malondialdehyde, total glutathione, Interleukin-1β and nuclear factor kappa-B levels were measured in the auditory nerve tissue. Our biochemical test results showed that paclitaxel significantly increased the amount of malondialdehyde in auditory nerve tissue compared to anakinra and healthy group (P < 0.0001), whereas total glutathione level decreased. In addition, paclitaxel was found to increase interleukin-1β and nuclear factor kappa-B significantly compared to anakinra and healthy group (P < 0.0001). It was concluded that anakinra is effective in suppressing paclitaxel related oxidative stress and proinflammatory events in auditory nerve tissue.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2020The effect of rhodiola rosea root extract on stress-induced ovarian damage, infertility and reproductive disorders in female rats
Kadioglu, B.G.; Gundogdu, B.; Kurt, N.; Ozbek Bilgin, A.; Suleyman, Halis; Suleyman, Z.
Purpose: The aim of the study was to examine the possible effect of Rhodiola rosea root extract (RRE) on ovarian damage, infertility (IF), delay in conception (DC), decrease in the number of offspring (NO) in female rats that have been stressed with compulsory immobilization method (CIM) and on retardation of intrauterine physical development (IPD) in offspring. Materials and methods: Female Albino Wistar rats were divided like: healthy (HG), stress-induced control (SC), and stress + 50 mg/kg RRE (S + REG) groups including sixteen rats in each group. Six rats from each group were killed for conducting biochemical and histopathological examinations in ovarian tissues and others were observed for IF, DC, NO, and IPD. Results: It was found that RRE significantly prevented the increase in oxidative parameters and proinflammatory cytokine levels in ovarian tissue of animals stressed with CIM. RRE suppressed the increase in IF rate and DC whereas caused a decrease in NO and in IPD retardation. Conclusion: These results suggested RRE may have beneficial effects in the treatment of stress induced reproductive dysfunction. Content: The effect of RRE on oxidative and inflammatory changes in ovarian tissue and reproductive changes of animals exposed to stress with compulsory immobilization method.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2020The effect of cerebrolysin on cisplatin-induced oxidative acoustic nerve injury in rats
Erhan, Ertugrul; Bayram, Rana; Suleyman, Bahadir; Kurt, Nezahat; Suleyman, Halis; Salcan, Ismail
One of the major side effects of dose-limiting cisplatin is ototoxicity, resulting in restricted clinical use. Cerebrolysin is a neuroprotective, neurotrophic and antioxidant drug derived from the brains of pigs. No studies have investigated the positive effects of Cerebrolysin on the damage to auditory nerves caused by cisplatin- induced oxidative stress. Eighteen rats were randomly divided into three groups of six: the Cerebrolysin and cisplatin group (CCG), the cisplatin group (CG) and the healthy group (HG). The CCG was administered 2.5 mL/kg of Cerebrolysin via subcutaneous injection daily, while the CG and HG were administered physiological saline solutions daily. Every other day, after receiving their dose of Cerebrolysin or physiological saline solution, the CCG and CG groups were administered 5 mg/kg of cisplatin via intraperitoneal injection (IP) every other day. The substances were administered for eight days. In acoustic nerve tissue, while the CCís oxidant parameters were significantly higher (p < 0.0001) than those of the CCG and HG groups, its antioxidant parameters were also significantly lower (p < 0.0001). Cerebrolysin antagonized the balance of oxidants and antioxidants in acoustic nerve tissue, resulting in higher concentrations of oxidants. The results suggested that Cerebrolysin may be useful in the treatment of cisplatin-induced oxidative acoustic nerve injury.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2020Effects of adenosine triphosphate on methanol-induced experimental optic nerve damage in rats: biochemical and histopathological evaluation
Icel, Erel; Suleyman, Halis; Yazici, Gulce Naz; Bakan, Nuri; Sunar, Mukadder
Purpose: Acute methanol exposure leads to systemic intoxication and toxic optic neuropathy. In this experimental study, we aimed to determine the protective effects of intravenous administration of ATP in methanol-induced optic neuropathy. Materials and methods: A total of 18 male albino Wistar rats weighing between 267 and 282 g were used for the experiment. The animals were divided into three groups as healthy control (HC), methanol (M), and methanol + ATP (M-ATP) groups. Distilled water was given to the healthy control group (n = 6) as the solvent, while 20% methanol was administered orally to the rats in M (n = 6) and M-ATP (n = 6) groups at a dose of 3 g/kg. Four hours after the administration of 20% methanol orally to the M-ATP group, ATP was injected intraperitoneally at a dose of 4 mg/kg. Eight hours after ATP injection, the animals were sacrificed by high-dose (50 mg/kg) thiopental anaesthesia and biochemical and histopathological examinations were performed on the removed optic nerve tissues. Malondialdehyde (MDA), total glutathione (tGSH), total oxidant status (TOS) and total anti-oxidant status (TAS) were analysed with biochemical tests. Results: MDA, TOS and OSI were significantly higher and tGSH and TAS levels were significantly lower in methanol administered group compared with the healthy controls or M-ATP group (p: 0.001). There was not any significant difference between healthy controls and M-ATP group regarding the oxidative stress parameters. There was a significant destruction and increase in thickness and astrocyte numbers and edema-vacuolization in methanol administered group compared with the healthy controls or M-ATP group (p: 0.001). Conclusion: Intravenous ATP administration had a significant positive effect on the oxidative stress parameters and optic nerve structure in methanol-intoxicated rats. Antioxidant therapies should be considered in future studies as a possible therapy for methanol-induced toxic optic neuropathy.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2020Effect of desloratadine on oxidative and inflammatory ovarian ischemia-reperfusion injury in female rats biochemical and histopathological evaluation
Kadıoglu, Berrin Goktug; Gundogdu, Betul; Kurt, Nezahat; Suleyman, Halis; Suleyman, Zeynep
OBJECTIVE: To examine the effect of desloratadine on ovarian ischemia-reperfusion (I/R) injury in rats by biochemical and histopathological methods. STUDY DESIGN: I/R was induced in the right ovaries after distilled water was given to a group of female albino Wistar rats in this study. 15 mg/kg desloratadine was orally administered to another group and I/R was induced in their ovaries, whereas I/R was not induced in the sham operation group. After 2 hours of ischemia and 2 hours of reperfusion, malondialdehyde (MDA), total glutathione (tGSH), nuclear factor-κB (NF-κB), interleukin 1 beta (IL-1β), and tumor necrosis factor alpha (TNF-α) levels were measured in ovarian tissues extracted from the body of the animals sacrificed with a high dose of ketamine (120 mg/kg). Tissues were also evaluated histopathologically. RESULTS: It has been revealed that desloratadine significantly inhibited the increase of I/R-associated MDA, NF-κB, IL-1β, and TNF-α levels in the ovarian tissues of animals and the decrease in tGSH levels. In addition, desloratadine decreased severe I/R-associated histopathological damage. CONCLUSION: Our experimental results have shown that desloratadine is beneficial in terms of protecting ovarian tissue against I/R injury.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2020Effects of adenosine triphosphate on vandetanib induced skin damage in rats
Akagunduz, Baran; Ozcicek, Fatih; Kara, Ali Veysel; Guven, Deniz Can; Yazici, Gulce Naz; Çoban, Abdulkadir; Suleyman, Bahadır; Mammadov, Renad; Suleyman, Halis
Purpose: Vandetanib is a wide spectrum tyrosine kinase inhibitor used for the treatment of metastatic medullary thyroid cancer (MTC) and various other cancer types. Although it is usually well-tolerated ıt has been linked to a variety of severe dermatologic reactions. Our study aimed was to investigate adenosine 5′-triphosphate (ATP) on vandetanib-induced skin damage. Materials and methods: A total number of 18 rats were divided into three equal groups as vandetanib group (VDB), vandetanib plus ATP group (VAT), and healthy group (HG); 25 mg/kg ATP was injected intraperitoneally (ip) to the VAT group. Normal saline was given to the HG and VDB groups as solvent via intraperitoneally. One hour later, 25 mg/kg vandetanib was applied orally via an orogastric catheter in the VAT and VDB groups. This procedure was repeated once daily for 4 weeks. After that period, all animals were sacrificed and their skin tissues removed. Malondialdehyde (MDA), total glutathione (tGSH), total oxidant status (TOS), total antioxidant status (TAS) levels in rats’ skin tissues were evaluated with histopathological analyses. Results: MDA and TOS levels measured higher in the VDB group compared to the VAT and HG groups (p < 0.001). tGSH and TAS levels of the VDB group measured lower than the VAT and HG groups (p < 0.001). The structure and morphology of skin tissue were normal in the control group. In the VDB group, skin tissue damage with thinner epitelium, ruptured and degenerated hair follicles, abnormal accumulation of abnormal keratin on the epithelium and oedematous areas in the dermis was observed. In the VAT group, these findings were significantly improved. Conclusion: We demonstrated that adenosine triphosphate can prevent vandetanib-induced skin toxicity in rats for the first time. The promising results denote that further studies testing this agent in other animal models and in humans are warranted.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2020Effect of rutin on cytarabine-associated pulmonary oedema and oxidative stress in rats
Bilgin, Asli O.; Mammadov, Renad; Suleyman, Bahadir; Unver, Edhem; Ozcicek, Fatih; Soyturk, Mehmet; Cimen, Ferda K.; Kurt, Nezahat; Suleyman, Halis
Cytarabine is effectively used in the treatment of adult acute leukemia, but it has a dose-limiting side effect of fatal pulmonary oedema because it increases the vascular permeability of the alveolar capillaries. The aim of the present study was to conduct a radiological, biochemical and histopathological investigation of the effect of rutin on cytarabine-associated pulmonary oedema in rats. Rats were treated with a combination of rutin+cytarabine by administering oral rutin at a dose of 50 mg/kg; other rat groups were orally administered the same volume of physiological saline. One hour after administration of rutin or saline, the rutin+cytarabine and cytarabine groups received an intraperitoneal injection of cytarabine (200 mg/kg). This administration procedure was repeated once a day for 14 days. Radiologically, 50% of the animals given cytarabine alone showed lung oedema, but the rutin+cytarabine group showed no oedema. The inclusion of rutin decreased the amounts of cytarabine-associated malondialdehyde, tumour necrosis factor-α, and nuclear factor-κB in the lung tissue. Rutin also inhibited the reduction of total glutathione by nitric oxide. These findings suggest that rutin may be a beneficial adjunct that can minimise the development of cytarabine-associated pulmonary oedema.
RDL Kalıcı Kaydıİncele - ArticleYalnız künye2019Effect of Hippophae rhamnoides extract on Cisplatin-induced ototoxicity in Guinea Pigs
Erhan, Ertugrul; Mammadov, Renad; Altuner, Durdu; Cimen, Ferda; Kurt, Nezahat; Hacimuftuoglu, Fazil; Turan, Fatih; Terzi, Suat; Celiker, Metin; Suleyman, Halis
No previous studies have examined the effect of Hippophae rhamnoides fruit extract (HRE), which contains both water and fat soluble vitamins, on cisplatin-induced ototoxicity. Therefore, the aim of the study was to investigate the effects of FIRE on cisplatin-induced ototoxicity in Guinea pigs and to evaluate the biochemical, gene expression and histopathological changes associated with cisplatin use. Experimental animals were divided into three groups: healthy (HG), HRE+cisplatin (HRC) and cisplatin control (CCG) groups. Biochemical, gene expression and histopathological examinations were carried on the removed inner ear tissues. In the HRC group, the oxidant parameter was lower and the anti-oxidant parameter was higher than in the CCG. These results are supported by gene expression levels and histopathological results. The use of FIRE against cisplatin-induced oxidative ototoxicity may be easier, more cost effective and more beneficial than the use of vitamins alone or in combination with each other.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2019Benidipine can prevent liver ischemia reperfusion injury in rats: a biochemical and histopathological evaluation
Cimen, Orhan; Eken, Hüseyin; Keskin Cimen, Ferda; Ozbek Bilgin, Asli; Pehlivanoglu, Kamil; Kurnaz, Eray; Gülaboglu, Mine; Suleyman, Bahadir; Suleyman, Halis
Ischemia reperfusion (IR) injury is defined as a pathological process which initiates with tissue deoxygenation, continues with oxidative stress, and spreads with inflammation. Increased intracellular calcium is responsible for oxidative stress and inflammation during this process. Benidipine is an antihypertensive drug acting as an T/L-type calcium channel blocker. The effect of benidipine on cyclooxygenase-2 (COX-2) activity is not known. Benidipine being a calcium channel blocker suggests that it may suppress oxidant and proinflammatory COX-2 production. The aim of this study was to examine the effect of benidipine on IR induced liver injury in albino Wistar male rats. Animals were divided into three groups: liver ischemia reperfusion (LIR), 2 mg/kg benidipine + liver ischemia reperfusion (BLIR), and sham surgery (SHAM). Hepatic artery, portal vein and bile duct were clamped to obtain ischemia for one hour and reperfusion for six hours. Malondialdehyde (MDA), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and COX-2 levels were higher, whereas total glutathione (tGSH) and cyclooxygenase-1 (COX-1) levels were lower in the LIR group. Liver tissue of the LIR group showed marked dilated congested blood vessels and increased bile duct proliferation, polymorphonuclear leukocyte infiltration, edema, hemorrhage and destruction. MDA, ALT, AST and COX-2 levels were lower, and tGSH and COX-1 levels were higher in the BLIR group treated with benidipine. Liver tissue of the BLIR group was found to be normal except for mild dilated blood vessels. These experimental findings indicate that benidipine may be useful in the treatment of liver IR injury.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2019The effect of resveratrol on oxidative ovary-damage induced by methotrexate in rats (Resveratrol oxidative ovary-damage)
Ata, Nahit; Kulhan, Nur G.; Kulhan, Mehmet; Turkler, Can; Kiremitli, Tunay; Kiremitli, Sevil; Cimen, Ferda Keskin; Suleyman, Halis; Toprak, Veysel
Methotrexate (MTX) is a commonly used folic acid antagonist for the treatment of neoplasia and some autoimmune diseases. Resveratrol has important anti-inflammatory, antioxidant and immunomodulatory properties. The aim of this study was to investigate the effects of resveratrol on MTX-induced ovary-damage and oxidative stress in rats. We hypothesized that supplement of resveratrol could counteract MTX-induced cytotoxicity in rat ovary. Albino Wistar female rats were randomly divided into three groups: Healthy control (HC), resveratrol + methotrexate (RMTX) and methotrexate (MTX) group. Their ovaries were removed. Biochemical and histopathological methods were utilized for evaluation of the oxidative ovary-damage. MDA was found to be higher but tGSH and SOD were lower in the ovarian tissue of the rat group administered MTX, but it is observed that these ratios are reversed in HC and in RMTX groups. MTX treatment induced ovary damage and especially pre-treatment with resveratrol provided protective effect against this MTX-induced ovary-damaged.
RDL Kalıcı Kaydıİncele - ArticleAçık Erişim2019Effect of ethyl acetate extract of usnea longissima o esophagogastric adenocarcinoma in rats
Mammadov, Renad; Suleyman, Bahadir; Altuner, Durdu; Demirci, Elif; Cetin, Nihal; Yilmaz, Adnan; Baykal, Huseyin; Alpcan, Hilal; Turumtay, Emine Akyuz; Suleyman, Halis
Purpose: To investigate the effects of the EtOAc extract of U. longissima which is uninvestigated previously on esophagogastric cancer induced in rats with N-methyl-N-nitro-N-nitrosoguanidin (MNNG). Methods: The anticancer activity of EtOAc extract of U. longissima was examined in the esophagogastric adenocarcinoma models induced in rats with MNNG. EtOAc extract of U. longissima, 50 and 100 mg/kg oral doses were administered once daily for six months. MNNG induced differentiated and undifferentiated type adenocarcinomas in the esophageal and gastric tissues of rats. Results: EtOAc extract of U. longissima obtained from U. longissima prevented gastric and esophageal cancerogenesis induced in rats with MNNG. EtOAc extract of U. longissima did not have a lethal effect at doses of 500, 1000 and 2000 mg/kg. The prominent anticarcinogenic activity of EtOAc extract of U. longissima 50 and 100 mg/kg suggests that it is not toxic and it is selective to the cancer tissue. Conclusion: This information may shed light on clinical implementation of EtOAc extract of U. longissima in future.
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