Fluvastatin suppresses oxidative stress and fibrosis in the interstitium of mouse kidneys with unilateral ureteral obstruction

Mori, Kiyoshi; Kawada, Noritaka; Nagatoya, Katsuyuki; Takeji, Masanobu; Horio, Masaru; Ando, Akio; Imai, Enyu; Hori, Masatsugu

doi:10.1046/j.1523-1755.2001.0590062095.x

Cited by 29 publications

(41 citation statements)

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“…10,29 As oxidative stress has been implicated in the pathophysiology of chronic pancreatitis 30,31 and antioxidant treatment can inhibit TGF-b release and thereby suppress pancreatic inflammation and fibrosis, 32 it is conceivable that pravastatin suppresses progression of pancreatic inflammation and fibrosis in this experimental model by attenuating oxidative stress. In support of our view, previous studies have shown that statins reduce fibrosis and inflammation along with an attenuation of oxidative stress in the kidney 4 and heart. 33 In this study, we found that treatment with pravastatin markedly increased production of IL-10 in the pancreas.…”

Section: Discussionsupporting

confidence: 90%

“…1 Therefore, statins are widely used in the first-line management of hyperlipidemia due to their efficacy in improving plasma lipid profiles. 1 However, as mevalonate is the precursor not only of cholesterol, but also of many non-steroidal compounds, inhibition of HMG-CoA by statins may result in pleiotropic effects such as anti-inflammatory, 2 anti-fibrotic 3 and antioxidative 4 actions.…”

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confidence: 99%

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Treatment with pravastatin attenuates progression of chronic pancreatitis in rat

Wei

Yamamoto

Harada

et al. 2011

Laboratory Investigation

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As appropriate therapies for pancreatic fibrosis and inflammation are limited, prognosis of chronic pancreatitis has not improved to date. Recent studies have shown that statins improve inflammation and fibrosis in several organs. We therefore examined the therapeutic effect of pravastatin on progression of chronic pancreatitis by starting this treatment after induction of pancreatic fibrosis in rats. Chronic pancreatitis was induced by continuous pancreatic ductal hypertension (PDH) for 14 days according to our previous study. Pravastatin at a dose of 10 mg/kg/day was administrated directly into the duodenum via cannula from 2 days after induction of PDH. Progression of pancreatic fibrosis and expression levels of transforming growth factor-b1 and tumor necrosis factor-a mRNA were markedly attenuated after commencement of pravastatin compared with untreated group with PDH. In addition, pravastatin treatment markedly improved pancreatic exocrine function and significantly elevated expression level of interleukin (IL)-10 and superoxide dismutase activity in the pancreas compared with the untreated group with PDH. These results revealed that pravastatin substantially attenuates the progression of pancreatic inflammation, fibrosis and exocrine dysfunction probably by its anti-oxidative property and overproduction of IL-10 in animal model of chronic pancreatitis. These results provide an experimental evidence that pravastatin exerts beneficial effect for progression of chronic pancreatitis.

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Section: Discussionsupporting

confidence: 90%

mentioning

confidence: 99%

Treatment with pravastatin attenuates progression of chronic pancreatitis in rat

Wei

Yamamoto

Harada

et al. 2011

Laboratory Investigation

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“…Inhibitors of hydroxymethylglutaryl-coenzyme A reductase such as statins, which are widely used to lower serum cholesterol, have been shown to reduce the progression of renal fibrosis and glomerulosclerosis upon unilateral urethral obstruction (34). Furthermore, statins prevented cardiac fibrosis in rabbits transgenic for ␤-myosin heavy-chain Q(403), a common model of hypertrophic cardiomyopathy (35).…”

Section: Discussionmentioning

confidence: 99%

Rho‐associated kinases are crucial for myofibroblast differentiation and production of extracellular matrix in scleroderma fibroblasts

Akhmetshina¹,

Dees²,

Pileckytė³

et al. 2008

Arthritis & Rheumatism

109

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Conclusion. Our findings demonstrate that Rock potently stimulates the differentiation of resting fibroblasts into myofibroblasts and the production of ECM at biologically relevant concentrations without cell toxicity. These findings, along with the beneficial effects of Rock inhibition on vascular disease, indicate that inhibition of Rock might be an interesting novel therapeutic approach for the treatment of SSc.

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“…Deficiency of an anti-oxidant enzyme catalase enhanced tubulointerstitial injury and fibrosis in UUO in mice (43). On the other hand, anti-oxidant agents, such fluvastatin and bioflavonoids, inhibited renal fibrosis in UUO (15,28). Therefore, anti-oxidant actions may represent one plausible mechanism by which CO inhibits renal tubulointerstitial fibrosis in UUO.…”

Section: Discussionmentioning

confidence: 99%

Protective effects of low-dose carbon monoxide against renal fibrosis induced by unilateral ureteral obstruction

Wang¹,

Lee²,

Kwak³

et al. 2008

American Journal of Physiology-Renal Physiology

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Tubulointerstitial fibrosis is a hallmark of chronic progressive kidney disease leading to end-stage renal failure. An endogenous product of heme oxygenase activity, carbon monoxide (CO), has been shown to exert cytoprotection against tissue injury. Here, we explored the effects of exogenous administration of low-dose CO in an in vivo model of renal fibrosis induced by unilateral ureteral obstruction (UUO) and examined whether CO can protect against kidney injury. UUO in mice leads to increased extracellular matrix (ECM) deposition and tubulointerstitial fibrosis within 4 to 7 days. Kidneys of mice exposed to low-dose CO, however, had markedly reduced ECM deposition after UUO. Moreover, low-dose CO treatment inhibited the induction of α-smooth muscle actin (α-SMA) and major ECM proteins, type 1 collagen and fibronectin, in kidneys after UUO. In contrast, these anti-fibrotic effects of CO treatment were abrogated in mice carrying null mutation of Mkk3, suggesting involvement of the MKK3 signaling pathway in mediating the CO effects. Additionally, in vitro CO exposure markedly inhibited TGF-β1-induced expression of α-SMA, collagen, and fibronectin in renal proximal tubular epithelial cells. Our findings suggest that low-dose CO exerts protective effects, via the MKK3 pathway, to inhibit development of renal fibrosis in obstructive nephropathy.

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Fluvastatin suppresses oxidative stress and fibrosis in the interstitium of mouse kidneys with unilateral ureteral obstruction

Cited by 29 publications

References 0 publications

Treatment with pravastatin attenuates progression of chronic pancreatitis in rat

Treatment with pravastatin attenuates progression of chronic pancreatitis in rat

Rho‐associated kinases are crucial for myofibroblast differentiation and production of extracellular matrix in scleroderma fibroblasts

Protective effects of low-dose carbon monoxide against renal fibrosis induced by unilateral ureteral obstruction

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