Evaluation by different mechanisms of the protective effects of vitamin B12 on methotrexate nephrotoxicity

Öztürk, Emel; Karabulut, Derya; Akın, Aynur; Kaymak, Emin; Kuloğlu, Nurhan; Yakan, Birkan

doi:10.1007/s10735-021-10027-9

Cited by 6 publications

(1 citation statement)

References 41 publications

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“…Because of this, MTX prevents the production of DNA, RNA, and protein, which ultimately results in death in the cells or tissues. [11,12] However, MTX has toxicity not only against malignant cells but also for healthy organs like the liver, [13] kidney, [14] testes, [15] and brain. [16] As a result, alleviating MTX's toxicity and understanding its adverse effects might lead to better treatment, higher adherence, and lower mortality.…”

Section: Effects Of Methotrexate and Morin On Enzyme Activitiesmentioning

confidence: 99%

The effects of morin and methotrexate on pentose phosphate pathway enzymes and GR/GST/TrxR enzyme activities: An in vivo and in silico study

Caglayan,

Temel,

Türkeş

et al. 2023

Archiv der Pharmazie

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In this study, the mechanisms by which the enzymes glucose‐6‐phosphate dehydrogenase (G6PD), 6‐phosphogluconate dehydrogenase (6PGD), glutathione reductase (GR), glutathione‐S‐transferase (GST), and thioredoxin reductase (TrxR) are inhibited by methotrexate (MTX) were investigated, as well as whether the antioxidant morin can mitigate or prevent these adverse effects in vivo and in silico. For 10 days, rats received oral doses of morin (50 and 100 mg/kg body weight). On the fifth day, a single intraperitoneal injection of MTX (20 mg/kg body weight) was administered to generate toxicity. Decreased activities of G6PD, 6PGD, GR, GST, and TrxR were associated with MTX‐related toxicity while morin treatment increased the activity of the enzymes. The docking analysis indicated that H‐bonds, pi–pi stacking, and pi–cation interactions were the dominant interactions in these enzyme‐binding pockets. Furthermore, the docked poses of morin and MTX against GST were subjected to molecular dynamic simulations for 200 ns, to assess the stability of both complexes and also to predict key amino acid residues in the binding pockets throughout the simulation. The results of this study suggest that morin may be a viable means of alleviating the enzyme activities of important regulatory enzymes against MTX‐induced toxicity.

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