Methotrexate: pentose cycle and oxidative stress

Babiak, Regina Maria V.; Campello, Annibal P.; Carnieri, Eva Gunilla Skare; Oliveira, Ma. Benigna M.

doi:10.1002/(sici)1099-0844(1998120)16:4<283::aid-cbf801>3.0.co;2-e

Cited by 141 publications

(100 citation statements)

References 29 publications

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“…In our study, mirtazapine significantly eliminated the inhibitor effect of methotrexate on GSH production. Studies in the literature have demonstrated that methotrexate reduces the levels of glutathione in liver cells 18 . A methotrexate-associated fall in glutathione levels leads to hepatocyte injury.…”

Section: Discussionmentioning

confidence: 99%

The effect of mirtazapine on methotrexate-induced toxicity in rat liver

Özoğul¹,

Kısaoğlu²,

Turan³

et al. 2013

ScienceAsia

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Methotrexate is used as a chemotherapeutic agent and its anti-oxidant activity is used to treat many cancer types. This study conducts a biochemical and histopathological investigation into whether mirtazapine has a protective effect on methotrexate-induced hepatotoxicity in rats. Distilled water was given to a healthy group intraperitoneally. Methotrexate alone was injected in the control group, again intraperitoneally. Mirtazapine and, 1 h later, methotrexate were given to the rats in the final group. This procedure was repeated over 7 days. In the control group rats receiving methotrexate, blood AST, ALT, and LDH levels were 227 ± 3 µmol/l, 85 ± 2 µmol/l, and 357 ± 13 µmol/l, respectively. In the rats receiving mirtazapine and methotrexate, these values were 152 ± 3 µmol/l, 25 ± 1 µmol/l, and 141 ± 15 µmol/l. In the healthy rat group, AST, ALT, and LDH levels were 136 µmol/l, 20 µmol/l, and 133 µmol/l, respectively. Histopathologically, apoptotic bodies with condensed cytoplasm, peripheral, and pyknotic nuclei in the hepatocytes, focal necrosis and intense inflammation in the interstitial areas were present in the control group. In the methotrexate and mirtazapine group, there were no apoptotic bodies or inflammation, only isolated necrosis in the hepatocytes. In conclusion, mirtazapine protected the liver against methotrexate toxicity.

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Section: Discussionmentioning

confidence: 99%

The effect of mirtazapine on methotrexate-induced toxicity in rat liver

Özoğul¹,

Kısaoğlu²,

Turan³

et al. 2013

ScienceAsia

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“…MTX suppresses the antioxidative system and enhances oxidative stress in many organs (Babiak et al, 1998). Therefore, RJ might have protective and decreasing effect on mucositis and oxidative stress.…”

Section: Introductionmentioning

confidence: 99%

Efficacy of royal jelly on methotrexate-induced systemic oxidative stress and damage to small intestine in rats

Kaynar¹,

Çetin²,

Hacioglu³

et al. 2012

Afr. J. Trad. Compl. Alt. Med.

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The aim of this present study is to investigate the mucositis caused by methotrexate (MTX), as well as whether the application of royal jelly (RJ) has a protective effect on oxidative stress. This present study included six groups each consisted of 12 Wistar rats. Distilled water (po: peroral) was given to the 1 st group as placebo for 10 days and MTX (20 mg/kg, intraperitoneal: ip) on the 7 th day. The 2 nd group received RJ (50mg/kg, po) for 10 days and normal saline (NS) instead of MTX. RJ (50mg/kg) was given to the 3 rd group for 10 days and MTX on the 7 th day. The 4 th group received RJ (100 mg/kg, po) for 10 days and NS was given intraperitoneally. RJ (100mg/kg) was given to the 5 th group for 10 days and a single dose of MTX. Distilled water was given to the 6 th (control) group for 10 days and intraperitoneal NS on the 7 th day. Malondialdehyde (MDA), glutathione peroxidase and superoxide dismutase were analyzed in blood samples on the 11 th day. Morphological and histopathological changes were examined in the intestinal tissue samples. Villus length and mucosal thickness, as well as the villus length/crypt ratio, were significantly decreased with MTX administration, and the semiquantitative histological evaluation (SQHE) score was measured high (p<0.001). In addition, a decrease in the antioxidant parameters and an increase in the MDA levels were identified. The villus length and SQHE were significantly different in the groups receiving RJ (p<0.001) as compared to the MTX group. Although RJ addition had no effect on the decreased mucosal thickness and villus/crypt ratio in MTX groups, it caused an improvement in the antioxidant levels and a remarkable decrease in MDA levels. Adding RJ has a decreasing effect on the MTX-induced intestinal damage and it has a suppressive effect on MTX-induced oxidative stress by means of increasing antioxidant enzyme activity and decreasing lipid peroxidation.

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“…MTX produces reactive oxygen species (ROS) and thus causes lipid peroxidation and leads to impairment in mitochondrial function. 15 Neutrophil infiltration and oxidative stress were suggested to cause MTX-induced nephrotoxicity in the rat. 16 Similarly, many nephrotoxic drugs including cisplatin and gentamicin are reported to damage the kidney by the production of ROS.…”

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confidence: 99%

Protective effect of propolis on methotrexate-induced kidney injury in the rat

2016

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Objectives Propolis is a potent antioxidant and a free radical scavenger. Pharmacological induction of heat shock proteins (HSPs) has been investigated for restoring normal cellular function following an injury. In this study, effect of propolis on HSP-70 expression in methotrexate-induced nephrotoxicity and direct preventive effect of propolis in this toxicity were investigated. Material and methods A total of 40 male Wistar albino rats were divided into four groups: Group 1 was the untreated control. On the eighth day of the experiment, groups 2 and 3 received single intraperitoneal injections of methotrexate (MTX) at 20 mg/kg. Groups 3 and 4 received 100 mg/kg/day propolis (by oral gavage) for 15 d by the first day of the experimental protocol. Then the rats were decapitated under ketamine esthesia and their kidney tissues were removed. HSP-70 expression, apoptosis, and histopathological damage scores were then compared. Results MTX caused epithelial desquamation into the lumen of the tubules, dilatation, and congestion of the peritubular vessels and renal corpuscles with obscure Bowman's space. The number of apoptotic cells (p ¼ 0.000) and HSP-70 (p ¼ 0.002) expression were increased in group 2. Propolis prevented the rise in number of apoptotic cells (p ¼ 0.017), HSP-70 (p ¼ 0.000) expression, and improved kidney morphology. Conclusions It was found that methotrexate gives rise to serious damage in the kidney and propolis is a potent antioxidant agent in preventing kidney injury. ARTICLE HISTORY

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Methotrexate: pentose cycle and oxidative stress

Cited by 141 publications

References 29 publications

The effect of mirtazapine on methotrexate-induced toxicity in rat liver

The effect of mirtazapine on methotrexate-induced toxicity in rat liver

Efficacy of royal jelly on methotrexate-induced systemic oxidative stress and damage to small intestine in rats

Protective effect of propolis on methotrexate-induced kidney injury in the rat

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