- Email: [email protected]
Letter by Namazi regarding article “Simvastatin attenuates cisplatin-induced kidney and liver damage in rats”
Toxicology 247 (2008) 161
Contents lists available at ScienceDirect
Toxicology journal homepage: www.elsevier.com/locate/toxicol
Letter to the Editor
Letter by Namazi regarding article “Simvastatin attenuates cisplatin-induced kidney and liver damage in rats” Sir, I read with great interest the article by Iseri et al. (2007). This work shows that simvastatin markedly suppresses the functional activity of neutrophils, which is underscored by reduced myeloperoxidase activity compared with a placebo. I would like to complete the discussion of Iseri et al. (2007) by introducing a major route through which simvastatin could suppress the activity of neutrophils. The recent focus on cisplatin-induced injury has been on interaction between neutrophils and endothelial cells. Transendothelial migration of neutrophils, with release of reactive oxygen species and cytokines, causes further damage to the injured tissue (Mishra et al., 2004; Kim et al., 2006). However, a key component in the pathogenesis of cisplatin-induced injury is the upregulation of surface adhesion molecules on the vascular endothelium and their subsequent interaction with the activated neutrophils (Li et al., 2005). The most important adhesion protein identified on neutrophils is the integrin lymphocyte function-associated antigen-1 (LFA-1; CD11a/CD18), which is the ligand for intercellular adhesion molecule-1 (ICAM-1) expressed on the endothelium. The LFA-1/ICAM-1 interaction is crucial for the ingress of neutrophils into the inflammatory sites (Haskard and Lee, 1992; Chen and Easton, 2007). Simvastatin down regulate the expression of ICAM1 and LFA-1, and through binding to LFA-1, they interfere with ICAM-1–LFA-1 interaction (Ahn et al., 2007; Pozo et al., 2006). This important mechanism should be borne in mind as the major mechanism for simvastatin-induced inhibition of neutrophil activity.
0300-483X/$ – see front matter © 2008 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.tox.2008.02.013
References Ahn, K.S., Sethi, G., Aggarwal, B.B., 2007. Simvastatin potentiates TNF-alpha-induced apoptosis through the down-regulation of NF-kappaB-dependent antiapoptotic gene products: role of IkappaBalpha kinase and TGF-beta-activated kinase-1. J. Immunol. 178 (4), 2507–2516. Chen, P.L., Easton, A., 2007. Apoptotic phenotype alters the capacity of tumor necrosis factor-related apoptosis-inducing ligand to induce human vascular endothelial activation. J. Vasc. Res. 45 (2), 111–122. Haskard, D.O., Lee, T.H., 1992. The role of leukocyte–endothelial interactions in the accumulation of leukocytes in allergic inflammation. Am. Rev. Respir. Dis. 145, 10–13. Iseri, S., Ercan, F., Gedik, N., et al., 2007. Simvastatin attenuates cisplatin-induced kidney and liver damage in rats. Toxicology 230 (2–3), 256–264. Kim, H., Park, J.H., Lee, E.H., et al., 2006. Granulocyte function is stimulated by a novel hexapeptide, WKYMVm, in chemotherapy-treated cancer patients. Exp. Hematol. 34 (4), 407–413. Li, S., Gokden, N., Okusa, M.D., et al., 2005. Anti-inflammatory effect of fibrate protects from cisplatin-induced ARF. Am. J. Physiol. Renal Physiol. 289 (2), F469–F480. Mishra, J., Mori, K., Ma, Q., et al., 2004. Neutrophil gelatinase-associated lipocalin: a novel early urinary biomarker for cisplatin nephrotoxicity. Am. J. Nephrol. 24 (3), 307–315. Pozo, M., de Nicolas, R., Egido, J., et al., 2006. Simvastatin inhibits the migration and adhesion of monocytic cells and disorganizes the cytoskeleton of activated endothelial cells. Eur. J. Pharmacol. 548 (1–3), 53–63.
Hamid Namazi ∗ Department of Orthopaedic Surgery, Shiraz University of Medical Sciences, Chamran Hospital, Shiraz, Iran ∗ Tel.:
+98 711 6246093; fax: +98 711 6246093. E-mail address: [email protected] 16 February 2008 Available online 4 March 2008
Contents lists available at ScienceDirect
Toxicology journal homepage: www.elsevier.com/locate/toxicol
Letter to the Editor
Letter by Namazi regarding article “Simvastatin attenuates cisplatin-induced kidney and liver damage in rats” Sir, I read with great interest the article by Iseri et al. (2007). This work shows that simvastatin markedly suppresses the functional activity of neutrophils, which is underscored by reduced myeloperoxidase activity compared with a placebo. I would like to complete the discussion of Iseri et al. (2007) by introducing a major route through which simvastatin could suppress the activity of neutrophils. The recent focus on cisplatin-induced injury has been on interaction between neutrophils and endothelial cells. Transendothelial migration of neutrophils, with release of reactive oxygen species and cytokines, causes further damage to the injured tissue (Mishra et al., 2004; Kim et al., 2006). However, a key component in the pathogenesis of cisplatin-induced injury is the upregulation of surface adhesion molecules on the vascular endothelium and their subsequent interaction with the activated neutrophils (Li et al., 2005). The most important adhesion protein identified on neutrophils is the integrin lymphocyte function-associated antigen-1 (LFA-1; CD11a/CD18), which is the ligand for intercellular adhesion molecule-1 (ICAM-1) expressed on the endothelium. The LFA-1/ICAM-1 interaction is crucial for the ingress of neutrophils into the inflammatory sites (Haskard and Lee, 1992; Chen and Easton, 2007). Simvastatin down regulate the expression of ICAM1 and LFA-1, and through binding to LFA-1, they interfere with ICAM-1–LFA-1 interaction (Ahn et al., 2007; Pozo et al., 2006). This important mechanism should be borne in mind as the major mechanism for simvastatin-induced inhibition of neutrophil activity.
0300-483X/$ – see front matter © 2008 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.tox.2008.02.013
References Ahn, K.S., Sethi, G., Aggarwal, B.B., 2007. Simvastatin potentiates TNF-alpha-induced apoptosis through the down-regulation of NF-kappaB-dependent antiapoptotic gene products: role of IkappaBalpha kinase and TGF-beta-activated kinase-1. J. Immunol. 178 (4), 2507–2516. Chen, P.L., Easton, A., 2007. Apoptotic phenotype alters the capacity of tumor necrosis factor-related apoptosis-inducing ligand to induce human vascular endothelial activation. J. Vasc. Res. 45 (2), 111–122. Haskard, D.O., Lee, T.H., 1992. The role of leukocyte–endothelial interactions in the accumulation of leukocytes in allergic inflammation. Am. Rev. Respir. Dis. 145, 10–13. Iseri, S., Ercan, F., Gedik, N., et al., 2007. Simvastatin attenuates cisplatin-induced kidney and liver damage in rats. Toxicology 230 (2–3), 256–264. Kim, H., Park, J.H., Lee, E.H., et al., 2006. Granulocyte function is stimulated by a novel hexapeptide, WKYMVm, in chemotherapy-treated cancer patients. Exp. Hematol. 34 (4), 407–413. Li, S., Gokden, N., Okusa, M.D., et al., 2005. Anti-inflammatory effect of fibrate protects from cisplatin-induced ARF. Am. J. Physiol. Renal Physiol. 289 (2), F469–F480. Mishra, J., Mori, K., Ma, Q., et al., 2004. Neutrophil gelatinase-associated lipocalin: a novel early urinary biomarker for cisplatin nephrotoxicity. Am. J. Nephrol. 24 (3), 307–315. Pozo, M., de Nicolas, R., Egido, J., et al., 2006. Simvastatin inhibits the migration and adhesion of monocytic cells and disorganizes the cytoskeleton of activated endothelial cells. Eur. J. Pharmacol. 548 (1–3), 53–63.
Hamid Namazi ∗ Department of Orthopaedic Surgery, Shiraz University of Medical Sciences, Chamran Hospital, Shiraz, Iran ∗ Tel.:
+98 711 6246093; fax: +98 711 6246093. E-mail address: [email protected] 16 February 2008 Available online 4 March 2008