Vasodilator agents protect against indinavir nephrotoxicity
Autor(a) principal: | |
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Data de Publicação: | 2003 |
Outros Autores: | |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | http://repositorio.unifesp.br/11600/42611 https://www.intmedpress.com/journals/avt/abstract.cfm?id=1046&pid=88 |
Resumo: | Indinavir (IDV) is a protease inhibitor widely used in AIDS treatment. A sustained elevation of creatinine was identified in IDV-treated patients. We have previously demonstrated that IDV causes renal vasoconstriction in rats. The objective of this study was to investigate the mechanism of IDV-induced vasoconstriction and the effect that the vasodilator agents L-arginine (LA), nifedipine (NF), as well as magnesium supplementation (Mg), have on IDV-induced nephrotoxicity. Male Wistar rats were kept on fast overnight and given free access to water. IDV (80 mg/kg BW) and NF (3 mg/kg BW) were given by gavage for 15 days. LA (1.5%) and MgCl(2)center dot 6H(2)O (11%) were added to drinking water. Six groups were studied: Control (n=6): normal rats treated with vehicle, a 0.05 M citric acid solution; IDV (n=7): IDV-treated rats; IDV+LA (n=6): IDV- and LA-treated rats; IDV+NF (n=7): IDV- and NF-treated rats; IDV+Mg (n=7): IDV- and MgCl2-treated rats; IDV+Mg+L-NAME (n=9): IDV- and MgCl2-treated rats, supplemented with L-NAME (2.5 mg/l in drinking water). Clearance studies and evaluations of urinary nitrite (NO2) excretion were performed on day 16. No changes in blood pressure were observed. NO2 excretion decreased in IDV-treated rats. LA and NF protected against IDV effects, improving GFR (IDV+LA, 1.95 +/-0.10; IDV+NF, 1.94 +/-0.07 vs IDV, 1.15 +/-0.07 ml/min, P<0.001) and RBF (IDV+LA, 7.83 +/-0.09; IDV+NF, 7.63 +/-0.14 vs IDV, 6.17 +/-0.25 ml/min, P<0.001). These results suggest that IDV-induced vasoconstriction is mediated by NO and Ca2+ channels. Magnesium also ameliorated GFR and RBF in IDV-treated rats (GFR IDV+Mg, 1.77 +/-0.08 ml/min, P<0.001; RBF IDV+Mg, 7.35 +/-0.158 ml/min, P<0.001). Magnesium protection is not NO-mediated since it was not blocked by L-NAME. In conclusion, LA, NF and Mg protect against IDV-induced nephrotoxicity in rats. This study may have potential clinical implications for prevention of IDV-induced nephrotoxicity. |
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Araujo, Magali de [UNIFESP]Seguro, Antonio CarlosUniversidade de São Paulo (USP)Universidade Federal de São Paulo (UNIFESP)2018-06-15T13:50:16Z2018-06-15T13:50:16Z2003-08-01Antiviral Therapy. London: Int Medical Press Ltd, v. 8, n. 4, p. 295-299, 2003.1359-6535http://repositorio.unifesp.br/11600/42611https://www.intmedpress.com/journals/avt/abstract.cfm?id=1046&pid=88WOS:000231266500005Indinavir (IDV) is a protease inhibitor widely used in AIDS treatment. A sustained elevation of creatinine was identified in IDV-treated patients. We have previously demonstrated that IDV causes renal vasoconstriction in rats. The objective of this study was to investigate the mechanism of IDV-induced vasoconstriction and the effect that the vasodilator agents L-arginine (LA), nifedipine (NF), as well as magnesium supplementation (Mg), have on IDV-induced nephrotoxicity. Male Wistar rats were kept on fast overnight and given free access to water. IDV (80 mg/kg BW) and NF (3 mg/kg BW) were given by gavage for 15 days. LA (1.5%) and MgCl(2)center dot 6H(2)O (11%) were added to drinking water. Six groups were studied: Control (n=6): normal rats treated with vehicle, a 0.05 M citric acid solution; IDV (n=7): IDV-treated rats; IDV+LA (n=6): IDV- and LA-treated rats; IDV+NF (n=7): IDV- and NF-treated rats; IDV+Mg (n=7): IDV- and MgCl2-treated rats; IDV+Mg+L-NAME (n=9): IDV- and MgCl2-treated rats, supplemented with L-NAME (2.5 mg/l in drinking water). Clearance studies and evaluations of urinary nitrite (NO2) excretion were performed on day 16. No changes in blood pressure were observed. NO2 excretion decreased in IDV-treated rats. LA and NF protected against IDV effects, improving GFR (IDV+LA, 1.95 +/-0.10; IDV+NF, 1.94 +/-0.07 vs IDV, 1.15 +/-0.07 ml/min, P<0.001) and RBF (IDV+LA, 7.83 +/-0.09; IDV+NF, 7.63 +/-0.14 vs IDV, 6.17 +/-0.25 ml/min, P<0.001). These results suggest that IDV-induced vasoconstriction is mediated by NO and Ca2+ channels. Magnesium also ameliorated GFR and RBF in IDV-treated rats (GFR IDV+Mg, 1.77 +/-0.08 ml/min, P<0.001; RBF IDV+Mg, 7.35 +/-0.158 ml/min, P<0.001). Magnesium protection is not NO-mediated since it was not blocked by L-NAME. In conclusion, LA, NF and Mg protect against IDV-induced nephrotoxicity in rats. This study may have potential clinical implications for prevention of IDV-induced nephrotoxicity.USP, Fac Med, Disciplina Nefrol, Lab Pesquisa Basica LIM12, BR-09500900 Sao Paulo, BrazilUniv Fed Sao Paulo, Sao Paulo, BrazilUniv Fed Sao Paulo, Sao Paulo, BrazilWeb of Science295-299engInt Medical Press LtdAntiviral TherapyVasodilator agents protect against indinavir nephrotoxicityinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP11600/426112021-10-05 22:00:45.602metadata only accessoai:repositorio.unifesp.br:11600/42611Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652021-10-06T01:00:45Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
Vasodilator agents protect against indinavir nephrotoxicity |
title |
Vasodilator agents protect against indinavir nephrotoxicity |
spellingShingle |
Vasodilator agents protect against indinavir nephrotoxicity Araujo, Magali de [UNIFESP] |
title_short |
Vasodilator agents protect against indinavir nephrotoxicity |
title_full |
Vasodilator agents protect against indinavir nephrotoxicity |
title_fullStr |
Vasodilator agents protect against indinavir nephrotoxicity |
title_full_unstemmed |
Vasodilator agents protect against indinavir nephrotoxicity |
title_sort |
Vasodilator agents protect against indinavir nephrotoxicity |
author |
Araujo, Magali de [UNIFESP] |
author_facet |
Araujo, Magali de [UNIFESP] Seguro, Antonio Carlos |
author_role |
author |
author2 |
Seguro, Antonio Carlos |
author2_role |
author |
dc.contributor.institution.none.fl_str_mv |
Universidade de São Paulo (USP) Universidade Federal de São Paulo (UNIFESP) |
dc.contributor.author.fl_str_mv |
Araujo, Magali de [UNIFESP] Seguro, Antonio Carlos |
description |
Indinavir (IDV) is a protease inhibitor widely used in AIDS treatment. A sustained elevation of creatinine was identified in IDV-treated patients. We have previously demonstrated that IDV causes renal vasoconstriction in rats. The objective of this study was to investigate the mechanism of IDV-induced vasoconstriction and the effect that the vasodilator agents L-arginine (LA), nifedipine (NF), as well as magnesium supplementation (Mg), have on IDV-induced nephrotoxicity. Male Wistar rats were kept on fast overnight and given free access to water. IDV (80 mg/kg BW) and NF (3 mg/kg BW) were given by gavage for 15 days. LA (1.5%) and MgCl(2)center dot 6H(2)O (11%) were added to drinking water. Six groups were studied: Control (n=6): normal rats treated with vehicle, a 0.05 M citric acid solution; IDV (n=7): IDV-treated rats; IDV+LA (n=6): IDV- and LA-treated rats; IDV+NF (n=7): IDV- and NF-treated rats; IDV+Mg (n=7): IDV- and MgCl2-treated rats; IDV+Mg+L-NAME (n=9): IDV- and MgCl2-treated rats, supplemented with L-NAME (2.5 mg/l in drinking water). Clearance studies and evaluations of urinary nitrite (NO2) excretion were performed on day 16. No changes in blood pressure were observed. NO2 excretion decreased in IDV-treated rats. LA and NF protected against IDV effects, improving GFR (IDV+LA, 1.95 +/-0.10; IDV+NF, 1.94 +/-0.07 vs IDV, 1.15 +/-0.07 ml/min, P<0.001) and RBF (IDV+LA, 7.83 +/-0.09; IDV+NF, 7.63 +/-0.14 vs IDV, 6.17 +/-0.25 ml/min, P<0.001). These results suggest that IDV-induced vasoconstriction is mediated by NO and Ca2+ channels. Magnesium also ameliorated GFR and RBF in IDV-treated rats (GFR IDV+Mg, 1.77 +/-0.08 ml/min, P<0.001; RBF IDV+Mg, 7.35 +/-0.158 ml/min, P<0.001). Magnesium protection is not NO-mediated since it was not blocked by L-NAME. In conclusion, LA, NF and Mg protect against IDV-induced nephrotoxicity in rats. This study may have potential clinical implications for prevention of IDV-induced nephrotoxicity. |
publishDate |
2003 |
dc.date.issued.fl_str_mv |
2003-08-01 |
dc.date.accessioned.fl_str_mv |
2018-06-15T13:50:16Z |
dc.date.available.fl_str_mv |
2018-06-15T13:50:16Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
Antiviral Therapy. London: Int Medical Press Ltd, v. 8, n. 4, p. 295-299, 2003. |
dc.identifier.uri.fl_str_mv |
http://repositorio.unifesp.br/11600/42611 https://www.intmedpress.com/journals/avt/abstract.cfm?id=1046&pid=88 |
dc.identifier.issn.none.fl_str_mv |
1359-6535 |
dc.identifier.wos.none.fl_str_mv |
WOS:000231266500005 |
identifier_str_mv |
Antiviral Therapy. London: Int Medical Press Ltd, v. 8, n. 4, p. 295-299, 2003. 1359-6535 WOS:000231266500005 |
url |
http://repositorio.unifesp.br/11600/42611 https://www.intmedpress.com/journals/avt/abstract.cfm?id=1046&pid=88 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartof.none.fl_str_mv |
Antiviral Therapy |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
295-299 |
dc.publisher.none.fl_str_mv |
Int Medical Press Ltd |
publisher.none.fl_str_mv |
Int Medical Press Ltd |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UNIFESP instname:Universidade Federal de São Paulo (UNIFESP) instacron:UNIFESP |
instname_str |
Universidade Federal de São Paulo (UNIFESP) |
instacron_str |
UNIFESP |
institution |
UNIFESP |
reponame_str |
Repositório Institucional da UNIFESP |
collection |
Repositório Institucional da UNIFESP |
repository.name.fl_str_mv |
Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP) |
repository.mail.fl_str_mv |
|
_version_ |
1802764166165954560 |