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Eur J Pharmacol ; 913: 174624, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34774496

RESUMO

Trimetazidine (TMZ) is a well-known anti-ischemic agent used for the treatment of angina pectoris. In the past decades, the efficacy of this drug has been tested in a wide range of kidney injuries, including drug-induced nephrotoxicity (DIN), radio-contrast agent-induced nephropathy, and surgically induced renal ischemic injury. TMZhas renoprotective effects by attenuating oxidative stress, inflammatory cytokine release, maintaining oxygen and energy balance. Moreover, TMZ administration prevented kidney graft rejection in the porcine model by suppressing the infiltration of mononuclear cells, preserving mitochondrial functions, and maintaining Ca+ homeostasis. In DIN and diabetic kidney diseases,TMZ treatment prevents renal injury by inactivating immune cells, attenuating renal fibrosis, inflammation, apoptosis, and histological abnormalities. Interestingly, the clinical therapeutic efficacy of TMZ has also been documented in pre-existing kidney disease patients undergoing contrast exposure for diagnostic intervention. However, the mechanistic insights into the TMZ mediated renoprotective effects in other forms of renal injuries, including type-2 diabetes, drug-induced nephrotoxicity, and hypertension-induced chronic kidney diseases, remain uninvestigated and incomplete. Moreover, the clinical utility of TMZ as a renoprotective agent in radio-contrast-induced nephrotoxicity needs to be tested in a large patient population. Nevertheless, the available pieces of evidence suggest that TMZ is a promising and emerging renal therapy for the treatment and management of kidney diseases of variable etiologies. This review discusses the various pre-clinical and clinical findings and provides mechanistic insights into the TMZ mediated beneficial effects in various kidney diseases.


Assuntos
Nefropatias/tratamento farmacológico , Rim/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Trimetazidina/farmacologia , Vasodilatadores/farmacologia , Animais , Ensaios Clínicos como Assunto , Avaliação Pré-Clínica de Medicamentos , Humanos , Rim/irrigação sanguínea , Rim/fisiopatologia , Nefropatias/fisiopatologia , Estresse Oxidativo , Substâncias Protetoras/uso terapêutico , Resultado do Tratamento , Trimetazidina/uso terapêutico , Vasodilatadores/uso terapêutico
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