Effect of methotrexate administration on status of some essential trace elements and antioxidant enzymes in pregnant rats in late gestation

Al-Saleh, Eyad; Al-Harmi, Jehad; Nandakumaran, Moorkath; Al-Shammari, Majed; Al-Jassar, Waleed

doi:10.3109/09513590903056811

Cited by 9 publications

(6 citation statements)

References 28 publications

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“…Methotrexate treatment increased Zn-SOD activity although it had no effect on GSH-Px activity in rats [24,25]. In the present study, methotrexate increased serum zinc levels in the patients with RA enhancing the activity of Zn-SOD [24,25]. No changes in serum copper and selenium levels were observed.…”

Section: Discussioncontrasting

confidence: 63%

“…It induces metallothionein synthesis, which has been shown to sequester free radicals [20]. Methotrexate treatment increased Zn-SOD activity although it had no effect on GSH-Px activity in rats [24,25]. In the present study, methotrexate increased serum zinc levels in the patients with RA enhancing the activity of Zn-SOD [24,25].…”

Section: Discussionmentioning

confidence: 42%

“…2 Serum selenium levels (mean ± SD) in patients with rheumatoid arthritis and healthy controls. a p<0.01 relative to controls [25] who reported that serum copper and selenium levels did not change in pregnant rats treated with methotrexate. Armagan et al [24] reported that methotrexate had no effect on GSH-Px activity in rat testis.…”

Section: Discussionmentioning

confidence: 82%

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Effects of Different Medical Treatments on Serum Copper, Selenium and Zinc Levels in Patients with Rheumatoid Arthritis

Önal

Nazıroğlu

Çolak

et al. 2010

Biol Trace Elem Res

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The aim of the present study was to measure the changes in serum selenium, zinc, and copper in patients being treated for rheumatoid arthritis. Thirty-two patients and 52 healthy controls were included in the study. The copper level was higher and those of selenium and zinc were lower in the patients relative to controls. Treatment with methotrexate elevated the zinc levels, but not zinc and selenium. Treatments with salazopyrin, corticosteroids, chloroquine, and non-steroidal anti-inflammatory drugs did not change the levels of any of the elements studied. The decrease in zinc and selenium levels and elevation in copper levels observed in the patients probably resulted from the defense response of organism and are mediated by inflammatory-like substances.

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Section: Discussioncontrasting

confidence: 63%

Section: Discussionmentioning

confidence: 42%

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Effects of Different Medical Treatments on Serum Copper, Selenium and Zinc Levels in Patients with Rheumatoid Arthritis

Önal

Nazıroğlu

Çolak

et al. 2010

Biol Trace Elem Res

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“…Surprisingly, GSH level, both in serum and liver showed elevation in the group treated with MTX, an effect unexpected from a cytotoxic drug and attributed to interference with GSH metabolism. 16,17 Regardless to the observed rise in GSH level, this did not stop MTX from damaging the liver; which may suggest mechanisms other than oxidant/antioxidant involved in MTX induced hepatotoxicity that cannot be opposed by MTX induced rise in GSH, and that all MTX treated rabbits showed hydropic degeneration on histopathological examination.…”

Section: Discussionmentioning

confidence: 82%

A study of the effect of Nigella Sativa (black seeds) on Methotrexate induced hepatotoxicity in rabbits.

Abbas

Ahmed

Al-Haroon

2015

Int J Basic Clin Pharmacol

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INTRODUCTION Methotrexate (MTX), an antimetabolite drug possess an indispensable place in the treatment of cancer, and many other common chronic inflammatory diseases such as rheumatoid arthritis and psoriasis. 1 In these diseases, MTX was used in low doses and described as having low profi le of toxicities, 2,3 however, at these doses, liver toxicity is still a major concern. 4 On the contrary, chronic use of MTX may result in serious toxic effects on many organs such as the gastrointestinal tract, liver, kidney, lung, and bone marrow. 5 Nigella sativa (NS) was found in many studies protective to the liver against many drugs such as INH 6 or chemicals as CCL 4. 7 NS, in addition has been used topically and orally and found benefi cial in ameliorating psoriatic lesions. 8,9 The study was, therefore, designed to investigate the protective effect of NS against MTX-induced hepatotoxicity in rabbits. METHODS Preparation of NS NS seeds were purchased from a local market for medicinal plants in Basrah, authenticated by an expert herbalist and a voucher specimen was kept in the Department of Pharmacology for future reference. Viability of the seeds was guaranteed by cultivating 100 seeds, implanted, a number of plants were counted and their growth was followed up. The seeds were crushed by electric grinder into a fi ne powder ABSTRACT Background: To evaluate the effectiveness of Nigella sativa (NS) in the prevention of hepatotoxicity of large doses of methotrexate (MTX) (IP) in rabbits. Methods: Three groups of male rabbits, six in each were used. Oral dosing was administered as a paste; formula 1 was prepared by mixing 2 g fl our with water; formula 2 contained fl our and NS and water. Group 1 was fed with formula 1 daily and injected with 2 ml/kg normal saline IP. Group 2 was given formula 1 daily with 20 mg/kg MTX IP. Group 3 was fed with formula 2 daily + MTX 20 mg/kg IP. Injections were given weekly for 5 weeks, and then the animals were sacrifi ced at day 39. Liver enzymes, malondialdehyde (MDA), glutathione (GSH), and histopathology of the liver were evaluated. Results: Liver enzymes, serum, and liver MDA were signifi cantly increased by MTX. MTX + NS treatment signifi cantly reduced the rise in liver enzymes, MDA in serum with little effect on liver MDA. Serum aspartate aminotransferase, alkaline phosphatase, and bilirubin were reduced from 82.8±18.04 U/L, 4.9±2.0 kind and king unit/100 ml and 0.74±0.1 mg/dl to 56.1±7.5, 2.0±0.6 and 0.27±0.1 respectively. Unexpectedly, serum and liver GSH were slightly increased by MTX. Treatment with MTX + NS further increased these levels. Histologically, portal and lobular sinusoidal dilatation, lymphocytic infi ltration, and hepatocyte hydropic degeneration were seen in all rabbits on MTX, which disappeared in three rabbits on NS + MTX. Conclusion: NS is hepatoprotective against MTX induced hepatotoxicity.

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“…In another study, SOD and GPX values were significantly higher, but TAC was significantly lower in MTX-treated animals as compared with the controls (p<0.05). 18 Further, Shema-Didi et al 19 showed that one-year pomegranate juice (PJ) intake decreased oxidative stress and inflammation in hemodialysis patients. While Faria et al 20 demonstrated the protective effect of PJ against systemic oxidative stress in mice.…”

Section: Resultsmentioning

confidence: 99%

Effects of Pomegranate (Punica Granatum L.) Seed and Peel Methanolic Extracts on Oxidative Stress and Lipid Profile Changes Induced by Methotrexate in Rats

Doostan¹,

Vafafar²,

Zakeri–Milani³

et al. 2017

Adv Pharm Bull

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Purpose: Methotrexate (MTX) is prescribed in many diseases and can result in oxidative stress (OS) followed by injuries in some tissues. Antioxidants administration are effective in reducing OS. Pomegranate exhibits high anti-oxidant capacities. This study investigated whether pomegranate seed and peel methanolic extracts (PSE and PPE) could protect against MTX-induced OS and lipid profile changes in rats.Methods: Forty-eight rats were randomly divided into 6 groups: control group (normal salin), PSE group (500 mg/kg, orally), PPE group (500 mg/kg, orally), MTX group (10 mg/kg, IM), MTX and PSE group, and MTX and PPE group. Blood samples were taken for analysis in the end of the procedure.Results: The findings showed a significant reduction in Glutathione peroxidase (GPx) and Superoxide dismutase (SOD), and an enhancement in malondialdehyde (MDA) values after MTX treatment (p < 0.05). SOD and GPx levels reached the levels of the control group in MTX+SPE and MTX+PPE groups. No significant differences were observed in catalase (CAT) and total antioxidant capacity (TAC) levels between groups. The results showed a significant decrease in total cholesterol (TC), low density lipoprotein (LDL), and high density lipoprotein (HDL) in the MTX treated group (p < 0.01). The values of TC, HDL, and LDL became elevated to the normal control levels in the MTX+PSE and MTX+PPE treated groups.Conclusion: The results showed the OS induced by MTX and the protective effects of PSE and PPE against MTX-induced serum oxidative stress and lipid profile changes in rats.

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Effect of methotrexate administration on status of some essential trace elements and antioxidant enzymes in pregnant rats in late gestation

Cited by 9 publications

References 28 publications

Effects of Different Medical Treatments on Serum Copper, Selenium and Zinc Levels in Patients with Rheumatoid Arthritis

Effects of Different Medical Treatments on Serum Copper, Selenium and Zinc Levels in Patients with Rheumatoid Arthritis

A study of the effect of Nigella Sativa (black seeds) on Methotrexate induced hepatotoxicity in rabbits.

Effects of Pomegranate (Punica Granatum L.) Seed and Peel Methanolic Extracts on Oxidative Stress and Lipid Profile Changes Induced by Methotrexate in Rats

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