Protective Effects of Alpha-Lipoic Acid on Methotrexate-Induced Oxidative Lung Injury in Rats

Arpağ, Hüseyin; Gül, Mehmet; Aydemir, Yusuf; Atilla, Nurhan; Yiğitcan, Birgül; Çakır, Tuğrul; Polat, Cemal; Þehirli, Özer; Sayan, Muhammet

doi:10.1080/08941939.2017.1296513

Cited by 34 publications

(35 citation statements)

References 38 publications

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“…This suggesting that peroxidative damage to tissues probably commenced after 2 weeks of MTX administration Coleshowers et al [45] . These findings were also similar to other study that stated that the tissue GSH levels in the MTX group were lower than those in the control group [46] . MTX-induced toxicity activates an inflammatory response and significantly increases the production of pro-inflammatory cytokines.…”

Section: Discussionsupporting

confidence: 92%

Structural and Behavioural Changes in Rat Hippocampus Induced by Methotrexate and The potential ameliorative effect of Alpha lipoic acid.

Alsemeh

Ibrahim

Mohammed

et al. 2019

Egyptian Journal of Histology

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Background: Methotrexate (MTX) is a chemotherapy drug associated with cognitive insufficiency in cancer patients treated with chemotherapy.. Alpha lipoic acid (ALA) has been referred to as the "universal antioxidant" because of its unique antioxidant properties. Aim: To inspect the effect of MTX on the hippocampus and to correlate them with the cognition impairment and to assess the practical neuroprotective role of ALA on hippocampus. Material and Method: Thirty two male adult albino were classified into four groups: control group (Physiologic saline), ALA group: (200 mg/kg orally for three weeks), MTX group: (250 mg/ kg) as a single dose intraperitoneally injected and MTX +ALA group: rats were administrated a single dose of intraperitoneal injection of MTX (250 mg/ kg) in the fourth day and were given ALA in a dose of 200 mg/kg orally for three weeks starting from the first day. All animals were subjected to Morris Water Maze testing to assess the hippocampus functions. At the end of the experiment, all animals anesthetized, cerebrum removed and the specimen subjected to histological procedures and biochemical examination. Results: MTX caused impaired performance of Morris Water Maze of rats and biochemical changes significant decrease in oxidative enzymes and increase in malondialdehyde (MDA) tissue levels. Moreover, MTX caused histological changes in rat hippocampus in the form of degenerative and apoptotic neurons which confirmed by immnnohistochemical staining of caspase-3 and GFAP staining and morphometrical analysis of pyramidal cell layer thickness and pyramidal cell count. Co-administration of ALA with MTX significantly diminished the behavioral affection and biochemical changes in rat treated with MTX and ameliorated the histological changes of hippocampus tissue. Conclusion: Our experimental results proved the harmful effect of MTX on hippocampus tissue that explained the cognitive impairment that associated with MTX and confirm the antioxidant and the antiapoptotic properties of ALA on hippocampus tissue.

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Section: Discussionsupporting

confidence: 92%

Structural and Behavioural Changes in Rat Hippocampus Induced by Methotrexate and The potential ameliorative effect of Alpha lipoic acid.

Alsemeh

Ibrahim

Mohammed

et al. 2019

Egyptian Journal of Histology

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“…Furthermore, oxidative stress is one of the main causes of lung injury induced by MTX. Long-term administration of MTX can induce severe interstitial pneumonia [32] and lung injury [33]. In the other way, it was reported that MTX could also cause severe gastrointestinal reaction.…”

Section: Discussionmentioning

confidence: 99%

Iridoid Glycosides From Morinda Officinalis F. C. How Alleviate Rheumatoid Arthritis and Its Associated Bone Deterioration and Protect Against Methotrexate-induced Toxicity in Collagen-induced Arthritic Rats

Shen

Zhang

et al. 2020

Preprint

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Background: Morinda officinalis F.C.How (MO), also known as “Ba-Ji-Tian” in Chinese, has long been used to treat osteoporosis and rheumatoid arthritis (RA) in China, knowing that iridoid glycosides (IG) isolated from this plant possess anti-inflammatory, anti-osteoporotic and analgesic activities. The study was to evaluate the ameliorating effect of MOIG on joint swelling and bone destruction and the protective effect against MTX toxicities.Methods: The anti-arthritic activity of MOIG was investigated by clinical arthritis scoring, paw swelling inspection, as well as histological analysis in CIA rats. The anti-bone loss activity of MOIG was evaluated by bone mineral density (BMD) and bone morphometric analysis assessed by Micro-CT and biochemical parameters in serum related with bone metabolism. The serum metabolomics and NF-κB signaling pathway were used to explore and clarify the action mechanism.Results: The results showed that MOIG was able to alleviate the paw swelling and arthritic severity, and reduce the synovial tissue proliferation and inflammatory cell infiltration in the CIA rats. In addition, MOIG decreased bone loss and improved the micro-structure of the bone trabecular in CIA rats through regulating bone formation and bone resorption. MOIG could also reduce effectively protect against MTX-induced damage to the liver, lung and stomach. The result of metabolomics analysis showed that MOIG was involved in the regulation of D-glutamine and D-glutamate metabolism, taurine and hypotaurine metabolism, valine, leucine and isoleucine biosynthesis, and alanine, aspartate and glutamate metabolism. Furthermore, MOIG inhibited OC formation and differentiation through participating in LPS-induced NF-κB signaling. Conclusion: MOIG could attenuate the paw swelling and bone loss through regulation of amino acid metabolism, reduce the side effects caused by MTX, and may serve as a novel therapeutic for the management of patients with rheumatoid arthritis (RA).

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“…This drug is used at low doses for the treatment of various inflammatory and autoimmune diseases, including rheumatoid arthritis, juvenile idiopathic arthritis and psoriasis, as well as at high doses for treating various types of cancers [2,3]. However, the efficiency of this agent at high doses or long-term therapy is related to its hepatotoxicity and some of the known side effects include hematologic complications, lung and intestinal toxicity [3,4]. The mechanism of liver damage caused by methotrexate has not been clearly specified; nevertheless, it has been reported that methotrexate causes oxidative stress and inflammation in the liver tissue.…”

Section: Introductionmentioning

confidence: 99%

Investigation of Protective Effect of Matricaria Chamomilla L. Extract on Methotrexate-Induced Hepatotoxicity in Wistar Rat

Afarani

Mohammadi

Shokri

et al. 2020

Braz. arch. biol. technol.

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Methotrexate (MTX) was shown to cause oxidative stress and liver damage. The objective was to investigate the possible protective effects of Matricaria Chamomilla L. (chamomile) extract with anti-oxidant and anti-inflammatory properties on the methotrexate-induced liver toxicity. Twenty four Wistar rats were divided into four groups. MTX group was injected intraperitoneally on days 7 and 14 with 20 mg/kg methotrexate. Groups CE200 (chamomile extract 200 mg/kg/day) and CE300 (chamomile extract 300 mg/kg/day) received the same dose of methotrexate added with chamomile extract orally for 15 days at 200 mg/kg and 300 mg/kg respectively and the last group was healthy control group. Results of biochemical analyses indicated serum liver biomarkers (aminotransferases), alkaline phosphatase (ALP), albumin, and liver content of anti-oxidant enzymes (catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px)), reduced glutathione (GSH) and total anti-oxidant capacity (TAC) significantly increased (P <0.05-0.001) to normal in the CE treated groups compared to those of the MTX group. Serum bilirubin and hepatic malondialdehyde (MDA) levels significantly increased (P ˂0.001) in MTX group compared to those of the control group and decreased in CE200 and CE300 groups compared to those of the MTX group. Histopathological study showed inflammatory damage, necrotic cells and lipid infiltration in MTX group. In the groups treated with the chamomile extract, a significant improvement was observed in liver tissue in response HIGHLIGHTS  The chamomile extract improved MTX-induced liver histopathological and biochemical changes.  The improvement was significant in the rats that were treated with higher dose of extract (CE300).  The extract enhanced anti-oxidant defense system and decreased MTX-induced oxidative damage. 2 Soltani, M.; et al.

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Protective Effects of Alpha-Lipoic Acid on Methotrexate-Induced Oxidative Lung Injury in Rats

Abstract: Oxidative damage of MTX in rat lung is partially reduced when combined with ALA.

Cited by 34 publications

References 38 publications

Structural and Behavioural Changes in Rat Hippocampus Induced by Methotrexate and The potential ameliorative effect of Alpha lipoic acid.

Structural and Behavioural Changes in Rat Hippocampus Induced by Methotrexate and The potential ameliorative effect of Alpha lipoic acid.

Iridoid Glycosides From Morinda Officinalis F. C. How Alleviate Rheumatoid Arthritis and Its Associated Bone Deterioration and Protect Against Methotrexate-induced Toxicity in Collagen-induced Arthritic Rats

Investigation of Protective Effect of Matricaria Chamomilla L. Extract on Methotrexate-Induced Hepatotoxicity in Wistar Rat

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