Salicylate-induced kidney mitochondrial permeability transition is prevented by cyclosporin A.

Abstract:

:The effect of salicylate, the active metabolite of aspirin (acetyl salicylic acid) in the presence of Ca2+ and phosphate on mitochondrial permeability transition (MPT) was studied. MPT is often associated with opening of a Ca2+ -induced pore. The opening of this pore leads to swelling, loss of mitochondrial membrane potential and release of accumulated Ca2+. In freshly isolated rat kidney mitochondria, salicylate (400 microM) in the presence of 20 nmol Ca2+/mg protein and 0.1 mM phosphate induced swelling, loss of mitochondrial membrane potential and release of accumulated Ca2+. All these changes were eliminated when cyclosporin A (1 microM), (a pore inhibitory agent) was included in the incubation medium. Unlike salicylate, unhydrolyzed aspirin (400 microM) induced these changes slightly. We concluded that salicylate acts as an activator of Ca2+ and phosphate in promoting the opening of kidney inner mitochondrial membrane pore. As a result a great consideration should be given to its toxicological effect.

journal_name

Toxicol Lett

journal_title

Toxicology letters

authors

Al-Nasser IA

doi

10.1016/s0378-4274(98)00373-7

keywords:

subject

Has Abstract

pub_date

1999-03-08 00:00:00

pages

1-8

issue

1

eissn

0378-4274

issn

1879-3169

pii

S0378-4274(98)00373-7

journal_volume

105

pub_type

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