Differential changes in the pharmacokinetics of statins in collagen-induced arthritis rats

Lin, Ching‐Hsuan; Hsu, Ke-Wei; Chen, Chia-Hao; Uang, Yow Shieng; Lin, Chun-Jung

doi:10.1016/j.bcp.2017.06.118

Cited by 18 publications

(13 citation statements)

References 47 publications

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“…Multiple preclinical and clinical studies have analysed the impact of different statins on RA . Statins are given to patients with RA because of their increased risk for cardiovascular complications .…”

Section: Statins In Ramentioning

confidence: 99%

“…Multiple preclinical and clinical studies have analysed the impact of different statins on RA. [21][22][23] Statins are given to patients with RA because of their increased risk for cardiovascular complications. 24 A cohort study that included patients with a diagnosis of hyperlipidaemia who started statin intake showed that the connection between lowering low-density lipoprotein cholesterol and cardiovascular events in RA was comparable to the association found in matched general controls.…”

Section: Statins In Ramentioning

confidence: 99%

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Immune modulatory effects of statins

2018

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SummaryDespite major advances in recent years, immunosuppressive regimens for multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus and graft-versus-host disease still have major adverse effects and immunomodulation rather than immune paralysis would be desirable. Statins inhibit the rate-limiting enzyme of the L-mevalonate pathway, the 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase. It was shown that blocking the L-mevalonate pathway reduces inflammation through effects on downstream metabolites of the pathway including farnesylpyrophosphates and geranylgeranylpyrophosphates, which are essential for the attachment of GTPases like RhoA, Rac and Ras to the cell membrane. Therefore, Lmevalonate pathway downstream products play critical roles in the different steps of an immune response including immune cell activation, migration, cytokine production, immune metabolism and survival. This review discusses the relevance of the different metabolites for the immunomodulatory effect of statins and connects preclinical results with data from clinical studies that tested statins for the treatment of different inflammatory diseases.

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Section: Statins In Ramentioning

confidence: 99%

Section: Statins In Ramentioning

confidence: 99%

Immune modulatory effects of statins

2018

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“…In addition to synovial inflammation and cartilage damage, systemic inflammation is a hallmark of RA that can lead to altered gene expression in many tissues [21,49] and contribute to neurodegeneration [30]. Hippocampal inflammation has been reported in patients with RA and in experimental RA [1].…”

Section: Discussionmentioning

confidence: 99%

“…Food and water were available ad libitum. CIA rats were induced according to the methods described previously [21]. In brief, an aliquot of 250 μL of the emulsion, containing equal parts of Freund's complete adjuvant and 2 mg/mL bovine type II collagen, was subcutaneously injected to the base of the tail of the rats.…”

Section: Induction Of Cia Ratsmentioning

confidence: 99%

“…Proinflammatory cytokines, such as interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6), are the important inflammation-related mediators regulating the disease state of RA [7]. These proinflammatory cytokines can systemically regulate the expression and/or activities of various proteins, including drug-metabolizing enzymes and membrane transporters [21,49]. The systemic inflammation occurred in RA may also play an important role in the pathogenesis of neurodegenerative diseases [30] and cognitive impairment [10].…”

Section: Introductionmentioning

confidence: 99%

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Changes of blood-brain-barrier function and transfer of amyloid beta in rats with collagen-induced arthritis

Lai

Wang

Zhang

et al. 2021

J Neuroinflammation

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Background Rheumatoid arthritis (RA) is characterized by synovial inflammation, cartilage damage, and systemic inflammation. RA is also associated with the occurrence of neuroinflammation and neurodegenerative diseases. In this study, the impacts of RA on the function of the blood-brain barrier (BBB) and the disposition of amyloid beta (Aβ), including BBB transport and peripheral clearance of Aβ, were investigated in rats with collagen-induced arthritis (CIA), an animal model with similarity to clinical and pathological features of human RA. Methods CIA was induced in female Lewis rats. In addition to neuroinflammation, the integrity and function of the BBB were examined. The expression of Aβ-transporting proteins at brain blood vessels was measured. Blood-to-brain influx and plasma clearance of Aβ were determined. Results Both microgliosis and astrogliosis were significantly increased in the brain of CIA rats, compared with controls. In terms of BBB function, the BBB permeability of sodium fluorescein, a marker compound for BBB integrity, was significantly increased in CIA rats. Moreover, increased expression of matrix metalloproteinase-3 (MMP-3) and MMP-9 and decreased expression of tight junction proteins, zonula occludens-1 (ZO-1) and occludin, were observed in brain microvessels of CIA rats. In related to BBB transport of Aβ, protein expression of the receptor of advanced glycation end product (RAGE) and P-glycoprotein (P-gp) was significantly increased in brain microvessels of CIA rats. Notably, much higher expression of RAGE was identified at the arterioles of the hippocampus of CIA rats. Following an intravenous injection of human Aβ, significant higher brain influx of Aβ was observed in the hippocampus of CIA rats. Conclusions Neuroinflammation and the changes of BBB function were observed in CIA rats. The increased RAGE expression at cerebral blood vessels and enhanced blood-to-brain influx of Aβ indicate the imbalanced BBB clearance of Aβ in RA.

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