Reperfusion injury is one of the main reasons of cardiac disease morbidity. Phytopharmaceuticals
are gaining importance in modern medicine of cardioprotection because of their multiplex
capacity. The aim of this study was to investigate the effect of diosgenin on the
inflammatory response induced by myocardial ischemia and reperfusion injury and the
role of mitochondrial ATP-sensitive potassium (mitoKATP) channels in this regard.
Wistar rats (250-300 g) were used in this study. The Langendorff-perfused hearts of
animals were subjected to a 30-min global ischemia followed by a 90-min reperfusion.
The lactate dehydrogenase (LDH) release was measured by spectrophotometry. The levels
of inflammatory mediators tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β),
and IL-6 in the supernatant of heart's left ventricle were measured using an enzyme-linked
immunosorbent assay rat specific ELISA kit. The LDH release into the coronary effluent
during reperfusion was significantly decreased, and cardiac contractility significantly
improved by diosgenin preadministration as compared with those of control or Cremophor-EL
(solvent of diosgenin) groups (398 ± 48 vs. 665 ± 65 or 650 ± 73 ml/min) (P < 0.01).
Administration of diosgenin before the main ischemia significantly reduced the levels
of IL-6 (P < 0.05), IL-1β, and TNF-α (P < 0.01) in the reperfusion phase of diosgenin-treated
hearts as compared with untreated control hearts. Inhibition of mitoKATP channels
by 5-hydroxydecanoate significantly reverses the cardioprotective effects of diosgenin
(P < 0.05). The findings of the present study indicate that preconditioning with diosgenin
may induce cardioprotective effect against reperfusion injury through reducing the
production of inflammatory mediators and activating the mitoKATP channels.