Role of methotrexate chronotherapy in collagen-induced rheumatoid arthritis in rats

Wang, X.; Yan, Xiuwei; Wang, F.; Ge, Fengmei; Li, Z.

doi:10.1007/s00393-016-0236-6

Cited by 25 publications

(22 citation statements)

References 29 publications

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“…IL-6 and other pro-inflammatory cytokines stimulate the synthesis of such ideal indicator in the hepatic cells [39,40] . Although MTX chronotherapy effectively lowered CPR and tumour necrosis factor-α (TNF-α) in rats with collagen induced-arthritis [41] , the highest level of CPR in the present study was in the MTX group. In harmony with our results, CRP and TNF-α were expressed immunohistochemically in the tubular epithelium of MTX-treated rats kidney [13] .…”

Section: Discussioncontrasting

confidence: 70%

Ameliorating Effect of Alpha-lipoic Acid on Methotrexate-induced Histological and Biochemical Changes in The Lung of Adult Albino Rat

Aidaros

Aziz

Sabry

et al. 2019

Egyptian Journal of Histology

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Background: Owing to its antioxidant, anti-inflammatory and anti-fibrotic properties, alpha-lipoic acid (ALA) has been evaluated in a diversity of degenerative diseases and experimental toxicological studies. Aim of the Work: This study was performed to assess the ability of ALA to reverse the histological and biochemical alterations that take place in the rat lungs after exposure to methotrexate. Materials and Methods: This study was done using thirty-two male Wistar albino rats (180-220 g). The animals were divided into four equal groups. The control group: received distilled water by oral gavage for ten days and injected intraperitoneally (i.p.) with1 ml of physiologic saline (0.09% NaCl) solution on the fourth day. ALA group: received ALA (200 mg/kg once daily) dissolved in distilled water and given by oral gavage for ten days. Methotrexate (MTX) group: injected with a single dose of 20mg/kg MTX i.p. on the fourth day of the study. MTX+ALA group: received an oral dose of ALA (200 mg/kg) for ten days and a single dose of MTX (20mg /kg) i.p. on the fourth day. By the end of the experiment, all the animals were anaesthetized using phenobarbital 3%. Blood samples were collected to measure c-reactive protein (CRP). The lungs were dissected out and prepared for tissue homogenates, routine histological study and caspase-3 immunohistochemical evaluation. Results: In the MTX group, there were high levels of CPR, glutathione (GSH) and malondialdehyde (MDA) with reduction of superoxide dismutase (SOD) and catalase (CAT) activities. Lung sections revealed marked inflammatory cells infiltration, thickening of interalveolar septa, congested blood vessels, intrapulmonary hemorrhages, abundant collagen fibers and significant expression of caspase-3. In ALA+MTX group, there was an overt improvement in lung histoarchitecture. Additionally, SOD activity. CRP, MDA levels and caspase-3 expression were significantly less. Conclusion: Administration of ALA can work against oxidative damage in the lung induced by MTX.

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Section: Discussioncontrasting

confidence: 70%

Ameliorating Effect of Alpha-lipoic Acid on Methotrexate-induced Histological and Biochemical Changes in The Lung of Adult Albino Rat

Aidaros

Aziz

Sabry

et al. 2019

Egyptian Journal of Histology

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“…Therefore, in vitro experimental results might not be consistent with those of in vivo experiments. Recent studies have revealed that the adrenal gland is often neglected in regulatory endocrine disruption screening and testing, even though it is the organ of the endocrine system that is most commonly the target of toxicity. The TP‐treated female rats showed a reduced mean ZF and an increased mean ZR compared with the respective control rats.…”

Section: Discussionmentioning

confidence: 99%

Toxic effects of triptolide on adrenal steroidogenesis in H295R cells and female rats

Cheng

et al. 2019

J Biochem & Molecular Tox

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Triptolide (TP), a major active ingredient of Tripterygium wilfordii, exerts potent immunosuppressive effects in the treatment of rheumatoid arthritis but is not widely used in clinical practice due to its multiorgan toxicity, particularly hepatotoxicity, nephrotoxicity, and reproductive toxicity. An LC-MS/MS approach was employed to explore the endocrine-disrupting effects of TP. The endocrine-disrupting effects of various concentrations (0-100 nM) of TP for 48 hour were firstly investigated using an in vitro model (H295R cell line). It was found that TP did not decrease cell viability.The transcriptional levels of steroidogenic enzymes in H295R cells were assessed by quantificational real-time polymerase chain reaction. The possible adrenal and endocrine effects of oral administration of TP (0, 50, and 500 μg/kg) for 28 days on both normal and collagen-induced arthritis (CIA) rats were also explored. The serum and adrenal tissue hormone levels (corticosterone and progesterone) and adrenal histopathology were analyzed, with the results that TP significantly decreased the level of cortisol in H295R cells and the level of plasma corticosterone in both normal and CIA rats. Histological alterations in adrenal cortex were observed at the dose of 500 μg/kg. Exposure to TP for 48 hour had an obvious inhibitory effect on the messenger RNA transcript levels of HSD3B2, CYP21A2, CYP17A1, and CYP11B1, which is essential for the synthesis of corticosteroids. In a word, TP leads to the disorder of corticosteroid synthesis and secretion, and corticosteroid may be a potential biomarker for the treatment of multiorgan toxicity of TP.

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“…IL-6, an important pro-inflammatory cytokine expressed in rheumatoid arthritis (OA) [ 30 ], mediates osteoclast activation, thus contributing to cartilage and bone breakdown and joint destruction. Previous studies have found that plasma IL-6 levels in rats with collagen-induced arthritis (CIA) were higher at almost every sampling time compared to those in normal rats, and IL-6 expression showed significant circadian rhythms, indicating higher levels during the light phase and lower levels during the dark phase [ 31 ]. Recent studies revealed a relationship between circadian rhythm and osteogenesis and osteoclastogenesis.…”

Section: Circadian Rhythm In Bonementioning

confidence: 99%

Circadian rhythms affect bone reconstruction by regulating bone energy metabolism

et al. 2021

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Metabolism is one of the most complex cellular biochemical reactions, providing energy and substances for basic activities such as cell growth and proliferation. Early studies have shown that glucose is an important nutrient in osteoblasts. In addition, amino acid metabolism and fat metabolism also play important roles in bone reconstruction. Mammalian circadian clocks regulate the circadian cycles of various physiological functions. In vertebrates, circadian rhythms are mediated by a set of central clock genes: muscle and brain ARNT like-1 (Bmal1), muscle and brain ARNT like-2 (Bmal2), circadian rhythmic motion output cycle stagnates (Clock), cryptochrome 1 (Cry1), cryptochrome2 (Cry2), period 1 (Per1), period 2 (Per2), period 3 (Per3) and neuronal PAS domain protein 2 (Npas2). Negative feedback loops, controlled at both the transcriptional and posttranslational levels, adjust these clock genes in a diurnal manner. According to the results of studies on circadian transcriptomic studies in several tissues, most rhythmic genes are expressed in a tissue-specific manner and are affected by tissue-specific circadian rhythms. The circadian rhythm regulates several activities, including energy metabolism, feeding time, sleeping, and endocrine and immune functions. It has been reported that the circadian rhythms of mammals are closely related to bone metabolism. In this review, we discuss the regulation of the circadian rhythm/circadian clock gene in osteoblasts/osteoclasts and the energy metabolism of bone, and the relationship between circadian rhythm, bone remodeling, and energy metabolism. We also discuss the therapeutic potential of regulating circadian rhythms or changing energy metabolism on bone development/bone regeneration.

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Role of methotrexate chronotherapy in collagen-induced rheumatoid arthritis in rats

Cited by 25 publications

References 29 publications

Ameliorating Effect of Alpha-lipoic Acid on Methotrexate-induced Histological and Biochemical Changes in The Lung of Adult Albino Rat

Ameliorating Effect of Alpha-lipoic Acid on Methotrexate-induced Histological and Biochemical Changes in The Lung of Adult Albino Rat

Toxic effects of triptolide on adrenal steroidogenesis in H295R cells and female rats

Circadian rhythms affect bone reconstruction by regulating bone energy metabolism

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