The Activities of Antioxidant Enzymes and the Level of Malondialdehyde in Cerebellum of Rats Subjected to Methotrexate: Protective Effect of Caffeic Acid Phenethyl Ester

Uzar, Ertuğrul; Koyuncuoğlu, Hasan Rıfat; Uz, Efkan; Yılmaz, H. Ramazan; Kutluhan, Süleyman; Kilbas, Serkan; Gültekin, Fatih

doi:10.1007/s11010-006-9196-5

Cited by 81 publications

(62 citation statements)

References 39 publications

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“…Experimental studies have demonstrated the increased production of oxygen free radicals following MTX treatment, and these free radicals may lead to mitochondrial functional impairment [11]. MTX-induced toxicity is characterized by activation of the in ammatory response and signi cantly increased production of pro-in ammatory cytokines [29]. MTX-induced renal damage is further exacerbated by subsequent neutrophil in ltration and oxidative stress contribute [13].…”

Section: Discussionmentioning

confidence: 99%

Carvacrol prevents methotrexate-induced renal oxidative injury and renal damage in rats

Bozkurt¹,

Em²,

Oktayoğlu³

et al. 2014

CIM

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TurkeyCarvacrol prevents methotrexateinduced renal oxidative injury and renal damage in rats AbstractPurpose: e purpose of this study was to investigate the e ect of carvacrol (CAR) on methotrexate (MTX)-induced renal damage in rats.Methods: Twenty-four male rats were equally divided into three groups: group I, control treatment; group II, MTX-treated; and group III, MTX+CAR-treated. A single dose of CAR (73 mg/kg) was administered intraperitoneally to group III on the rst day of the experiment and a single dose of MTX (20 mg/kg) was administered intraperitoneally to groups II and III on the second day of the experiment. Blood samples and kidney tissue were obtained from each animal on day 8 for the measurement of malondialdehyde (MDA), total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI). Light microscopy was used for histopathological examination of kidney specimens.Results: MDA, TOS and OSI levels were signi cantly greater in the group receiving MTX alone relative to the control animals, while the TAS level was signi cantly reduced in the MTX group compared with the control group. e administration of CAR was associated with signi cantly decreased MDA, TOS, and OSI levels and increased TAS levels relative to the rats treated with MTX alone. Animals treated with CAR exhibited decreased tubular degeneration and architectural impairment relative to animals treated with MTX alone; however, the di erence in histological scores did not meet the threshold of statistical signi cance. e folic acid antagonist methotrexate (MTX) is used clinically to inhibit the synthesis of purines and pyrimidines [1]. MTX is commonly used at high doses to limit the growth of malignancies, but may also be used at low doses in in ammatory diseases, including psoriasis and rheumatoid arthritis, to inhibit the proliferation of in ammatory leukocytes [2][3][4]. MTX remains an essential component of modern clinical therapy for acute lymphoblastic leukemia and is the primary treatment for malignant gestational trophoblastic disease [5]. In addition to anti-proliferative activity, MTX has antiin ammatory and immunomodulatory properties; however, cytotoxic e ects and other side e ects limit the e cacy of MTX as an anti-in ammatory. Signi cant side e ects of MTX have been described in several organ systems. In particular, MTX has a detrimental e ect on kidney function [6]; however, the mechanism of MTX-induced toxicity remains unclear. More than 90% of MTX is ltered by the kidneys [7] and MTX treatment is known to cause renal failure at high doses [8]. Renal impairment can result in altered metabolism of MTX, delayed drug excretion and, subsequently, systemic toxicity. e toxic e ects of MTX are typically treated through hydration and alkalinization of the patient; however, these methods are insu cient to prevent all instances of MTX toxicity. Reactive oxygen species (ROS) have been implicated in the pathogenesis of MTX-induced renal damage [9,10]. MTX produces free oxygen radicals, resulting in enhanced li...

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Section: Discussionmentioning

confidence: 99%

Carvacrol prevents methotrexate-induced renal oxidative injury and renal damage in rats

Bozkurt¹,

Em²,

Oktayoğlu³

et al. 2014

CIM

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“…Group 2: MTX group (n=7): A single dose of 20 mg/kg of MTX was administered I.P. Because, it was revealed in previous studies that this dose (20 mg/kg) causes tissue toxicity [19] . MTX was dissolved in physiological saline.…”

Section: Groupmentioning

confidence: 99%

Ratlarda Metoraksat Kaynaklı Testiküler Toksisite Üzerine Hesperidinin Etkisi

Belhan¹,

Özkaraca²,

Kandemir³

et al. 2017

Kafkas Univ Vet Fak Derg

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Citation of This ArticleBelhan S, Özkaraca M, Kandemir FM, Gülyüz F, Yıldırım S, Ömür AD, Yener Z: Effectiveness of hesperidin on methotrexate-induced testicular toxicity in rats. Kafkas Univ Vet Fak Derg, 23 (5): 789-796, 2017789-796, . DOI: 10.9775/kvfd.2017 AbstractThe aim of this study was to investigate the effect of hesperidin on male reproductive system in rats to which methotrexate (MTX) was administered. In the study, 28 male Wistar albino rats at the age of 8 weeks and had 250-300 g of live weight were used. Four experimental groups were formed; Group 1 (n=7): The control group, only feed and water were given. Group 2 (n=7): MTX group, a single dose of 20 mg/ kg of i.p. MTX was administered. Group 3 (n=7): Hesperidin group, 200 mg/kg of hesperidin was administered by gavage for 7 days. Group 4: MTX + hesperidin group (n=7): Following administration of a single dose of 20 mg/kg i.p. MTX , 200 mg/kg of Hesperidin was administered by oral gavage for 7 days. At the end of the experiment, rats were decapitated and biochemical, histopathological and spermatological parameters were examined. It was observed that in the MTX group, sperm motility and density, the enzymes CAT, GPx and SOD and GSH level decreased, TNF-alpha and IL-1 Beta, as well as MDA, levels were increased, regular structure of spermatogenic cells was impaired, and seminiferous tubules became necrotic and degenerative. It was determined that spermatological parameters improved and, necrotic and degenerative changes diminished by the administration of MTX+hesperidin. These outcomes indicated that hesperidin had a protective effect on destructive effects of MTX in rat testiclesv. Keywords: Male rat, Hesperidin, Methotrexate, Sperm, Reproductive system Ratlarda Metoraksat Kaynaklı Testiküler Toksisite Üzerine Hesperidinin Etkisi ÖzetBu çalışmanın amacı, metoraksat (MTX) uygulanan ratlarda hesperidinin erkek üreme sistemi üzerindeki etkisini araştırmaktı. Çalışmada 8 haftalık yaşta, 250-300 g canlı ağırlığa sahip 28 erkek Wistar albino cinsi rat kullanıldı. Dört deney grubu oluşturuldu; Grup 1 (n=7): kontrol grubu, sadece yem ve su verildi. Grup 2 (n=7): MTX grubu, 20 mg/kg MTX i.p. tek doz uygulandı. Grup 3 (n=7): Hesperidin grubu, 200 mg/kg hesperidin 7 gün süre ile ağızdan sonda yardımıyla verildi. Grup 4 (n=7): MTX + hesperidin grubu, 20 mg/kg MTX i.p tek doz uygulamasını takiben 200 mg/kg hesperidin 7 gün süre ile ağızdan sonda yardımıyla verildi. Deney sonunda ratlar dekapite edilerek biyokimyasal, histopatolojik ve spermatolojik parametreler incelendi. MTX grubunda sperm motilitesi ve yoğunluğunun, CAT, GPx ve SOD enzimlerinin ve GSH düzeyinin düştüğü, TNF-alpha ve IL-1 Beta ile MDA düzeyinin arttığı, spermatojenik hücrelerin düzenli yapısının bozulduğu, seminifer tubullerin nekrotik ve dejeneratif bir hal aldığı gözlendi. MTX + hesperidin uygulaması ile spermatolojik parametrelerin düzeldiği, nekrotik ve dejeneratif değişikliklerin azaldığı tespit edildi. Bu sonuçlar hesperidinin rat testislerinde MTX tarafından oluşan yıkıcı etkiler üze...

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“…Uzar et al (27) reported that CAPE significantly reduced the activities of antioxidant enzymes and the level of malondialdehyde in the cerebellum of rats subjected to methotrexate. Ginis et al (13) reported that pretreatment with CAPE might protect brain tissue against ifosfamide-induced central neurotoxicity.…”

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confidence: 99%

Protective effects of intralipid and caffeic acid phenyl esther (cape) on neurotoxicity induced by ethanol in rats

Başarslan¹,

Osun²,

Şenol³

et al. 2015

Turkish Neurosurgery

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ABSTRACToxygen species (ROS) and free radicals are generated during ethanol metabolism, causing oxidative stress and lipid peroxidation in the liver, brain, heart and skeletal muscles (1,6,18,21).Mitochondria are major targets for ethanol toxicity in the liver, brain, heart, skeletal muscles, and exocrine pancreas (4). Ramachandran et al (23) showed in their study that utilized cultured fetal rat cortical neurons that ethanol elicits a rapid onset of oxidative stress, which culminates in mitochondrial mediated apoptotic cell death. Animal studies have found that long-term ethanol intoxication is not necessary to cause brain █ INTRODUCTION E thanol, is a colorless liquid with the structural formula CH 3 CH 2 OH, often abbreviated as C 2 H 5 OH or C 2 H 6 O. It is also used as a psychoactive drug and is one of the oldest recreational drugs still used by humans. Ethanol can cause alcohol intoxication when consumed.Alcoholic patients can develop not only liver lesions but also pancreatitis, brain damage, peripheral neuropathy, cardiomyopathy, and skeletal muscle myopathy (18,23). Reactive AIm: Ethanol causes oxidative degradation of the mitochondrial genome in the brain. This effect could contribute to the development of brain injury in some alcoholic patients. We investigated the protective effect of caffeic acid phenyl esther (CAPE) and intralipid (IL) on oxidative stress and neurotoxicity induced by ethanol intake. mATERIAl and mEThODS:The forty-eight rats were randomly divided into seven groups. Ethanol was administered for acute toxicity. IL and CAPE were administered immediately after ethanol intake. Total oxidant status (TOS), total antioxidant status (TAS), and oxidative status index (OSi) were evaluated and histologic examination of cerebellum and brain tissue with Hematoxylin-Eosin and immuno-histochemical dyes was performed. RESUlTS:In the ethanol group, TAS levels were significantly lower than the other groups and this finding indicates that the toxic effect of ethanol reduces antioxidant levels. In the ethanol group, TOS levels were significantly higher than the other groups. These results showed that ethanol induced oxidative stress. IL treatment increased TAS levels, and CAPE decreased TOS levels against ethanol toxicity. There was correlation between TAS and TOS levels. Also, histopathologic results confirmed these biochemical results.CONClUSION: CAPE and IL treatment could be effective course of therapy to enhance therapeutic efficacy and may provide a promising approach for the treatment of neurotoxicity and oxidative stress induced by ethanol in clinic.

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The Activities of Antioxidant Enzymes and the Level of Malondialdehyde in Cerebellum of Rats Subjected to Methotrexate: Protective Effect of Caffeic Acid Phenethyl Ester

Cited by 81 publications

References 39 publications

Carvacrol prevents methotrexate-induced renal oxidative injury and renal damage in rats

Carvacrol prevents methotrexate-induced renal oxidative injury and renal damage in rats

Ratlarda Metoraksat Kaynaklı Testiküler Toksisite Üzerine Hesperidinin Etkisi

Protective effects of intralipid and caffeic acid phenyl esther (cape) on neurotoxicity induced by ethanol in rats

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