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Telmisartan use in rats with preexisting osteoporotics bone disorders increases bone microarchitecture alterations via PPARγ.
Birocale, Antonio Marcos; Ferreira de Melo, Antonio; Peixoto, Pollyana; Costalonga Oliveira, Phablo Wendell; Gonçalves Ruffoni, Leandro Dias; Takayama, Liliam Masako; Nogueira, Breno Valentim; Nonaka, Keico Okino; Rodrigues Pereira, Rosa Maria; Martins de Oliveira, José; Bissoli, Nazaré Souza.
Afiliación
  • Birocale AM; Department of Health Integrated Education, Federal University of Espirito Santo, Vitória, ES, Brazil.
  • Ferreira de Melo A; Department of Physiological Sciences, Federal University of Espirito Santo, Vitória, ES, Brazil.
  • Peixoto P; Department of Physiological Sciences, Federal University of Espirito Santo, Vitória, ES, Brazil.
  • Costalonga Oliveira PW; Department of Physiological Sciences, Federal University of Espirito Santo, Vitória, ES, Brazil.
  • Gonçalves Ruffoni LD; Department of Physiological Sciences, Federal University of São Carlos, São Carlos, SP, Brazil.
  • Takayama LM; Department of Medical Clinic, Medicine College, University of São Paulo, São Paulo, SP, Brazil.
  • Nogueira BV; Department of Morphology, Federal University of Espirito Santo, Vitoria, ES, Brazil.
  • Nonaka KO; Department of Physiological Sciences, Federal University of São Carlos, São Carlos, SP, Brazil.
  • Rodrigues Pereira RM; Department of Medical Clinic, Medicine College, University of São Paulo, São Paulo, SP, Brazil.
  • Martins de Oliveira J; Laboratory of Applied Nuclear Physics, University of Sorocaba, Sorocaba, SP, Brazil.
  • Bissoli NS; Department of Physiological Sciences, Federal University of Espirito Santo, Vitória, ES, Brazil. Electronic address: nazarebissoli@gmail.com.
Life Sci ; 237: 116890, 2019 Nov 15.
Article en En | MEDLINE | ID: mdl-31606379
AIMS: Telmisartan (TEL), an angiotensin II type I receptor blocker and PPARγ partial agonist, has been used for to treat hypertension. It is known that PPARγ activation induces bone loss. Therefore, we evaluate the effects of telmisartan on PPARγ protein expression, biomechanics, density and bone microarchitecture of femurs and lumbar vertebrae in SHR ovariectomized animals, a model of hypertension in which preexisting bone impairment has been demonstrated. MAIN METHODS: SHR females (3 months old) were distributed into four groups: sham (S), sham + TEL (ST), OVX (C) and OVX + TEL (CT). TEL (5 mg/kg/day) or vehicle were administered according to the groups. After the protocol, blood pressure was measured and density, microarchitecture and biomechanics of bone were analyzed. Western blotting analysis was performed to evaluate PPARγ protein expression in the bones. KEY FINDINGS: Castration induced a deleterious effect on mineral density and trabecular parameters, with telmisartan enhancing such effects. Telmisartan increased PPARγ levels, which were at their highest when the treatment was combined with castration. As to biomechanical properties, telmisartan reduced the stiffness in the castration group (CT vs. S or C group), as well as resilience and failure load in ST group (vs. all others groups). SIGNIFICANCE: These results demonstrated that telmisartan compromised bone density and microarchitecture in animals that shows preexisting osteoporotic bone disorders, probably via mechanisms associated with increased PPARγ. If this translates to humans, a need for greater caution in the use of telmisartan by patients that have preexisting bone problems, as in the postmenopausal period, may be in order.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osteoporosis / Enfermedades Óseas / Regulación de la Expresión Génica / PPAR gamma / Bloqueadores del Receptor Tipo 1 de Angiotensina II / Hueso Esponjoso / Telmisartán Tipo de estudio: Guideline / Prognostic_studies Límite: Animals Idioma: En Revista: Life Sci Año: 2019 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osteoporosis / Enfermedades Óseas / Regulación de la Expresión Génica / PPAR gamma / Bloqueadores del Receptor Tipo 1 de Angiotensina II / Hueso Esponjoso / Telmisartán Tipo de estudio: Guideline / Prognostic_studies Límite: Animals Idioma: En Revista: Life Sci Año: 2019 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Países Bajos