HMG-COA reductase inhibitors: An opportunity for the improvement of imatinib safety. An experimental study in rat pulmonary hypertension

Jasińska-Stroschein, Magdalena; Owczarek, Jacek; Surowiecka, Anna; Kącikowska, Joanna; Orszulak–Michalak, Daria

doi:10.1016/j.pharep.2014.07.011

Cited by 6 publications

(5 citation statements)

References 26 publications

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“…In our previous study we demonstrated rosuvastatin to exert a moderate impact on hemodynamics and RV hypertrophy in rats with MCT-induced PH. The mean RVP values (47.7 mm Hg) observed in MCT-induced rats receiving rosuvastatin at 10 mg/kg for 14 days were only 26.5% lower than those receiving the vehicle on day 29 of the experiment [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

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Rosuvastatin intensifies the beneficial effects of rho-kinase inhibitor in reversal of monocrotaline-induced pulmonary hypertension

Jasińska-Stroschein¹,

Owczarek²,

Sołtysiak³

et al. 2016

aoms

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IntroductionIt remains controversial whether statins have a beneficial effect on pulmonary arterial hypertension (PAH). This study is intended to evaluate whether statin, co-administered with Rho-kinase inhibitor, could enhance its efficacy. Although Rho-kinase inhibitors, including fasudil, have been reported to improve pulmonary hypertension in experimental and clinical studies, the combination of these agents has not been tested in the treatment of pulmonary hypertension (PH).Material and methodsThe effects of such a regimen on hemodynamics, right ventricle hypertrophy, and Rho-associated protein kinase (ROCK) activity in experimental monocrotaline (MCT)-induced pulmonary hypertension were examined. Fourteen days after monocrotaline injection (60 mg/kg), male rats were treated orally for another 14 days with fasudil (15 mg/kg per day), or with a combination of fasudil + rosuvastatin (10 mg/kg per day).ResultsThe drug combination reversed the MCT-induced increase in right ventricle pressure (RVP) and reduced right ventricular hypertrophy (RV/LV + S ratio) more than Rho kinase inhibitor alone. The simultaneous administration of fasudil and rosuvastatin caused a further decrease of RhoA kinase activity in isolated lung tissues as compared to fasudil alone.ConclusionsThe results indicate that rosuvastatin intensifies the beneficial effects of Rho-kinase inhibitor on the Rho/Rho-kinase pathway and such a combination may represent an option for the treatment of pulmonary arterial hypertension.

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Section: Discussionmentioning

confidence: 99%

“…Our previous experimental results [ 22 ] show that rosuvastatin may exert only a moderate impact on hemodynamics or myocardial hypertrophy improvement in an MCT rat model. According to our knowledge, the effects of a combined statin and Rho kinase inhibitor regimen have not been assessed in PH.…”

Section: Introductionmentioning

confidence: 99%

Rosuvastatin intensifies the beneficial effects of rho-kinase inhibitor in reversal of monocrotaline-induced pulmonary hypertension

Jasińska-Stroschein¹,

Owczarek²,

Sołtysiak³

et al. 2016

aoms

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“…between days 1 and 8 of pregnancy. 16 In Group 3, (Imatinib-40) 40 mg/kg imatinib was administered i.p. on the same days.…”

Section: Materials and Methods Animal Experiments And Drug Administrationmentioning

confidence: 99%

The effect of imatinib administered in the prenatal period on testis development in rats

et al. 2020

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Background: The purpose of this study was to examine the effects of exposure to imatinib in the prenatal period on testis development in rats. Methods: Although all the study groups received intraperitoneal imatinib on prenatal days 1–8, no pregnancy occurred in the Imatinib-80 group. Immunohistochemical analysis, TUNEL, c-kit and PDGF staining revealed no difference between the groups in terms of positivity scoring. Results: A significant decrease was detected in total sperm counts in the Imatinib-20 group compared to the control group, but the sperm count was higher in the Imatinib-60 group than in the Imatinib-20 group. At biochemical measurements, the drug increased oxidative stress in the testis and serum in the Imatinib-20 group, but caused a decrease in tissue in the Imatinib-60 group. Thiol measurements revealed a decrease in the testis and serum in the Imatinib-60 group, while an increase in serum measurements was observed in the Imatinib-40 group. Analysis revealed no difference between the groups in terms of protamine and histone gene expression levels in testis tissue exposed to imatinib. Conclusion: Our findings show that prenatal exposure to imatinib can lead to histopathological and biochemical changes in testis tissue, but that no adverse effect occurs in nuclear maturation of germ cells during spermiogenesis.

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“… 48 A recent research confirmed that combination of statins with imatinib showed an enhanced effect in PH treatment, and statins can improve imatinib safety. 49 Combining drugs of different mechanisms to achieve greater therapeutic effects is beneficial for PH treatment. Therefore, combining statins with prostacyclin analogs, endothelin receptor antagonists, and phosphodiesterase type 5 inhibitors should be considered a possible therapeutic strategy.…”

Section: Possible Mechanisms Of Statins In the Treatment Of Phmentioning

confidence: 99%

Are statins beneficial for the treatment of pulmonary hypertension?

Wang

Yang

Wang

2017

Chronic Diseases and Translational Medicine

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Pulmonary hypertension (PH) is a condition characterized by vasoconstriction and vascular remodeling with a poor prognosis. The current medical treatments available are supportive care therapy and pulmonary vascular-targeted therapy. Targeted treatments for PH include prostacyclin analogs, endothelin receptor antagonists, and phosphodiesterase type 5 inhibitors; however, these treatments cannot reverse pulmonary vascular remodeling. Recently, many novel treatment options involving drugs such as statins have been emerging. In this review, we attempt to summarize the current knowledge of the role of statins in PH treatment and their potential clinical effects. Many basic researches have proved that statins can be helpful for the treatment of PH both in vitro and in experimental models. The main mechanisms underlying the effects of statins are restoration of endothelial function, attenuation of pulmonary vascular remodeling, regulation of gene expression, regulation of intracellular signaling processes involved in PH, anti-inflammatory responses, and synergy with other targeted drugs. Nevertheless, clinical researches, especially randomized controlled trials for PH are rare. The current clinical researches show contrasting results on the clinical effects of statins in patients with PH. Carefully designed randomized, controlled trials are needed to test the safety and efficacy of statins for PH treatment.

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HMG-COA reductase inhibitors: An opportunity for the improvement of imatinib safety. An experimental study in rat pulmonary hypertension

Cited by 6 publications

References 26 publications

Rosuvastatin intensifies the beneficial effects of rho-kinase inhibitor in reversal of monocrotaline-induced pulmonary hypertension

Rosuvastatin intensifies the beneficial effects of rho-kinase inhibitor in reversal of monocrotaline-induced pulmonary hypertension

The effect of imatinib administered in the prenatal period on testis development in rats

Are statins beneficial for the treatment of pulmonary hypertension?

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