High-dose atorvastatin causes regression of endometriotic implants: a rat model

Öktem, M.; Esinler, İbrahim; Eroğlu, Derya; Haberal, Nihan; Bayraktar, Nilüfer; Zeyneloglu, Hulusi Bulent

doi:10.1093/humrep/del505

Cited by 75 publications

(60 citation statements)

References 35 publications

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“…The sinvastatin used in the dose of 20 mg/kg/day during 14 days showed a significant regression of the focus of autotransplants when comparing the final volumes between the experimental and the control group 1 . Studies that used atorvastatin in high doses showed similar results 13 ; results that are compatible with our research on copaiba oil.…”

Section: Discussionsupporting

confidence: 91%

Changes in the volume and histology of endometriosis foci in rats treated with copaiba oil (Copaiferalangsdorffii)

Neto

Lindoso²,

Coelho³

et al. 2011

Acta Cir. Bras.

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PURPOSE: The aim of this study was to analyze the changes that occur in rats with experimental endometriosis after treatment with copaiba oil. METHODS: Experimental endometriosis was induced in rats. The experimental group received copaiba oil (Copaiferalangsdorffii) orally (0.63 mg/day), and the control group received a 0.9% sodium chloride solution orally (1 ml/100 g of body weight/day). Both groups were treated with gavage for 14 days. After this period, the animals were euthanized, and the implant volume was calculated. The autologous transplants were removed, dyed with hematoxylin-eosin, and analyzed by light microscopy. RESULTS: The average final volumes were significantly different between the groups (p=0.007). There was a significant increase (p=0.012) between the initial and final volumes in the control group, whereas treatment with Copaiferalangsdorffii caused a marked reduction in endometrial growth over time (p=0.016). Histologically, 6/11 (55.00%) rats in the experimental group had a well-preserved epithelial layer, and 3 (45.00%) had mildly preserved epithelium. The control group had seven cases (58.30%) of well-preserved epithelial cells and five cases (41.70%) of mildly preserved epithelial cells (p>0.05). CONCLUSION: Copaiba oil (Copaiferalangsdorffii) appears to be a promising alternative treatment for endometriosis.

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Section: Discussionsupporting

confidence: 91%

Changes in the volume and histology of endometriosis foci in rats treated with copaiba oil (Copaiferalangsdorffii)

Neto

Lindoso²,

Coelho³

et al. 2011

Acta Cir. Bras.

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“…10 Similarly, in homologous model of endometriosis, whereby rats underwent surgical establishment of autologous uterine tissues to ectopic sites, atorvastatin (2.5 mg/kg) therapy led to a significant reduction of the mean area of endometriotic implants. 22 The proposed mechanisms of actions of statins on endometriosis implants are stimulation of apoptosis, inhibition of endometrial cell proliferation, blockage of angiogenesis, disruption of adherence and invasion of endometrial cells to peritoneum, and decrease in oxidative stress and inflammation. 10,[22][23][24][25][26] Decreased sensitivity of endometrial tissue to spontaneous apoptosis contributes to the implantation and growth of endometrium at ectopic sites.…”

Section: Discussionmentioning

confidence: 99%

“…22 The proposed mechanisms of actions of statins on endometriosis implants are stimulation of apoptosis, inhibition of endometrial cell proliferation, blockage of angiogenesis, disruption of adherence and invasion of endometrial cells to peritoneum, and decrease in oxidative stress and inflammation. 10,[22][23][24][25][26] Decreased sensitivity of endometrial tissue to spontaneous apoptosis contributes to the implantation and growth of endometrium at ectopic sites. 27 Ectopic endometriosis implants demonstrate high ERK1/2 signaling pathway activity resulting in enhanced cell survival.…”

Section: Discussionmentioning

confidence: 99%

“…10 Statins may also protect from development of endometriotic implants by reducing angiogenesis, as demonstrated in animal endometriosis models and in cell culture. 10,22,23 Statins may block angiogenesis by decreasing MCP-1-induced vascular endothelial growth factor by endometrial stromal cells. 16 These observations are consistent with other reports documenting statin-induced inhibition of angiogenesis in models such as a xenograft model of human colon cancer in mice and myocardial ischemia in swine.…”

Section: Discussionmentioning

confidence: 99%

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Statins Inhibit Monocyte Chemotactic Protein 1 Expression in Endometriosis

et al. 2012

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Statins are potent inhibitors of the endogenous mevalonate pathway. Besides inhibiting cholesterol biosynthesis, statins may also demonstrate anti-inflammatory properties. Inflammation is implicated in the attachment and invasion of endometrial cells to the peritoneal surface and growth of ectopic endometrium by inducing proliferation and angiogenesis. In this study, the effect of statins on monocyte chemotactic protein 1 (MCP-1) expression in endometriotic implants in nude mouse model and in cultured endometriotic cells was evaluated. In mouse model, simvastatin decreased MCP-1 expression in a dose-dependent manner in endometriotic implants (P < .05). Similarly, both simvastatin and mevastatin revealed a dose-dependent inhibition of MCP-1 production in cultured endometriotic cells (P < .01). This inhibitory effect of the statins on MCP-1 production was reversed by the downstream substrates of the mevalonate pathway. Moreover, statins decreased MCP-1 messenger RNA expression in cultured endometriotic cells (P < .05). In conclusion, statins exert anti-inflammatory effect in endometriotic cells and could provide a potential treatment of endometriosis in the future.

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“…The animals were anesthetized with intraperitoneal injection of 50mg/kg ketamine and xylazine 7mg/kg 14 . The animals were attached to the surgical table in the supine position, the legs in abduction.…”

Section: Methods Methods Methods Methodsmentioning

confidence: 99%

Efeito do anti-TNF-α em implantes endometriais no peritônio de ratas

Kondo¹,

Lago²,

Noronha³

et al. 2011

Rev. Col. Bras. Cir.

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OBJETIVO: Avaliar o efeito da terapia anti-TNF-α no tratamento de implantes endometriais no peritônio de ratas. MÉTODOS: Os implantes endometrióticos foram induzidos cirurgicamente em 120 ratas Wistar-Albino. Os animais foram aleatoriamente distribuídos em 4 grupos. O grupo C (n=36) recebeu uma injeção intraperitoneal de 0,2ml de solução salina. O grupo L (n=41) recebeu uma injeção subcutânea de 1mg/kg de leuprolide. O grupo I5 (n=20) recebeu uma injeção subcutânea de 5mg/kg de anticorpo monoclonal anti-fator de necrose tumoral (TNF) a (infliximab). O grupo I10 (n=20) recebeu uma injeção subcutânea de 10mg/kg de infliximab. As ratas foram sacrificadas após 21 dias para se avaliar o tamanho dos implantes e a expressão do TNF-α. RESULTADOS: O tratamento com leuprolide promoveu uma redução absoluta na área de superfície do implante comparado com o grupo C (+14mm vs. 0mm; p=0,013) e com o grupo I10 (+14mm vs. +5mm; p=0,018). Da mesma forma, uma redução percentual da area de superfície do implante foi observada comparando o grupo L com o grupo C (+33,3% vs. 0%; p=0,005) e com o grupo I10 (+33,3% vs. +18,3%; p=0,027). O tratamento com infliximab não foi capaz de diminuir a área de superfície do implante comparado com o grupo C. A expressão de TNF-α reduziu nos grupos L, I5 e I10 comparado com o grupo C (505,6µm² vs. 660,5µm² vs. 317,2µm² vs. 2519,3µm², respectivamente; p<0,001). CONCLUSÃO: A terapia anti-TNF-α reduziu a expressão de TNF-α nos implantes endometrióticos mas não reduziu a área de superfície da lesão.

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High-dose atorvastatin causes regression of endometriotic implants: a rat model

Abstract: High-dose atorvastatin caused a significant regression of endometriotic implants.

Cited by 75 publications

References 35 publications

Changes in the volume and histology of endometriosis foci in rats treated with copaiba oil (Copaiferalangsdorffii)

Changes in the volume and histology of endometriosis foci in rats treated with copaiba oil (Copaiferalangsdorffii)

Statins Inhibit Monocyte Chemotactic Protein 1 Expression in Endometriosis

Efeito do anti-TNF-α em implantes endometriais no peritônio de ratas

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