Effect of Administration Duration of Low Dose Methotrexate on Development of Acute Kidney Injury in Rats

Li, Xiao; Abe, Erika; Yamakawa, Yukako; Yoneda, Go; Fujino, Rika; Yamashita, Mami; Iida, Yuumi; Jono, Hirofumi; Saito, Hideyuki

doi:10.4172/2472-1220.1000130

Cited by 10 publications

(10 citation statements)

References 22 publications

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“…After different MTX treatments in rats, some studies employed novel biomarkers to assess renal damage, besides measuring the traditional ones (such as blood urea nitrogen and plasma creatinine). They reported the increase of KIM-1 in renal tissue 30,31 and an augmented urinary NAG 32 and Cys C. 33 On the other hand, Carvalho Pedrosa et al 34 showed a direct correlation between MTX serum levels and urinary KIM-1 levels 24 hours after MTX infusion in paediatric patients. In the same way, plasma Cys C was useful to evaluate the renal performance before and after the infusion of HDMTX in paediatric patients with acute lymphoblastic leukaemia.…”

Section: Discussionmentioning

confidence: 99%

Time evolution of methotrexate‐induced kidney injury: A comparative study between different biomarkers of renal damage in rats

Severin

Campagno

Brandoni

et al. 2019

Clin Exp Pharma Physio

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Methotrexate (MTX) is commonly used in the treatment of malignant diseases and autoimmune and chronic inflammatory disorders. Along with its effective therapeutic power, MTX has adverse effects on the kidneys. Discovery of new biomarkers is required to improve the early detection of renal damage and optimize the effectiveness of treatments. The aim of this study was to evaluate the time course of MTX‐induced nephrotoxicity and to compare the urinary excretion of the organic anion transporter 5 (uOat5) with alterations in other markers of renal function, and to elucidate the possible molecular mechanisms involved in uOat5. Animals were exposed to a unique dose of MTX (80 mg/kg body weight, intraperitoneal). Experiments were carried out at days 2, 4, 8 or 14 after MTX administration. Markers of renal damage, such as creatinine and urea plasma levels, urinary activity of alkaline phosphatase, microalbuminuria, urinary excretion of neutrophil gelatinase‐associated lipocalin (uNGAL) and histopathology, were evaluated. Renal organic anion transporter 5 (Oat5) expression and its presence in different urine fraction were assessed by western blotting. uOat5 was significantly increased 2 days after MTX treatment, before than any alteration in other parameters of kidney injury or renal morphology occurred. uNGAL showed an inverted pattern of urinary excretion compared to uOat5. Exosomal pathway is involved in the urinary excretion of Oat5 and depends on the degree of damage induced by MTX. These experimental data allow proposing uOat5 as a potential non‐invasive biomarker for early detection of MTX‐induced nephrotoxicity.

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Section: Discussionmentioning

confidence: 99%

Time evolution of methotrexate‐induced kidney injury: A comparative study between different biomarkers of renal damage in rats

Severin

Campagno

Brandoni

et al. 2019

Clin Exp Pharma Physio

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“…It was also suggested that MTX-associated renal injury may by mediated through the induction of adenosine plasma concentration and subsequent activation of A1 receptors in renal parenchyma, reducing renal blood flow and thereby diminishing renal function [167]. Recently, using a rat model with renal failure caused by low-dose MTX administration, Li et al demonstrated that long-MTX administration caused MTX accumulation in renal tissue and severe glomerular and tubular injury through an increase in oxidative stress [168].…”

Section: Mtx Adverse Effects Mechanisms Of Actionmentioning

confidence: 99%

Methotrexate an Old Drug with New Tricks

Bedoui

Guillot

Sélambarom

et al. 2019

IJMS

329

192

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Methotrexate (MTX) is the first line drug for the treatment of a number of rheumatic and non-rheumatic disorders. It is currently used as an anchor disease, modifying anti-rheumatic drug in the treatment of rheumatoid arthritis (RA). Despite the development of numerous new targeted therapies, MTX remains the backbone of RA therapy due to its potent efficacy and tolerability. There has been also a growing interest in the use of MTX in the treatment of chronic viral mediated arthritis. Many viruses—including old world alphaviruses, Parvovirus B19, hepatitis B/C virus, and human immunodeficiency virus—have been associated with arthritogenic diseases and reminiscent of RA. MTX may provide benefits although with the potential risk of attenuating patients’ immune surveillance capacities. In this review, we describe the emerging mechanisms of action of MTX as an anti-inflammatory drug and complementing its well-established immunomodulatory activity. The mechanisms involve adenosine signaling modulation, alteration of cytokine networks, generation of reactive oxygen species and HMGB1 alarmin suppression. We also provide a comprehensive understanding of the mechanisms of MTX toxic effects. Lastly, we discussed the efficacy, as well as the safety, of MTX used in the management of viral-related rheumatic syndromes.

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“…The inhibition of methotrexate to immunity appears to increase the infections because of low white blood cell count leading to acute pneumonitis and rarely pulmonary fibrosis (5). It has been reported the present of methotrexate crystals in the renal tubules especially when it is administrated at high doses cause severe renal toxicity and acute renal failure considering the most important side effect (6). Methotrexate increases the reactive oxygen species in renal tissues; therefor it has been reported to reduce the methionine synthesis and antioxidant enzymes such as catalase and glutathione peroxidase (7).…”

Section: Introductionmentioning

confidence: 99%

Effect of methotrexate and aspirin interaction and its relationship to oxidative stress in rats

Alabdaly¹,

Saeed²,

Al-hashemi³

2021

IJVS

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Effect of Administration Duration of Low Dose Methotrexate on Development of Acute Kidney Injury in Rats

Cited by 10 publications

References 22 publications

Time evolution of methotrexate‐induced kidney injury: A comparative study between different biomarkers of renal damage in rats

Time evolution of methotrexate‐induced kidney injury: A comparative study between different biomarkers of renal damage in rats

Methotrexate an Old Drug with New Tricks

Effect of methotrexate and aspirin interaction and its relationship to oxidative stress in rats

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