Melatonin protects against oxidative mitochondrial damage induced in rat placenta by ischemia and reperfusion

Abstract

We assessed the effects of melatonin, a powerful scavenger of oxygen free radicals, on ischemia/reperfusion-induced oxidative damage to mitochondria in the rat placenta. In Wistar rats at day 19 of pregnancy, feto-placental ischemia was induced by occluding both utero-ovarian arteries for 20 min. Reperfusion was achieved by releasing the occlusion and restoring circulation for 30 min. Melatonin solution or the vehicle alone was injected intraperitoneally at dose of 10 mg/kg 1 hr before occlusion. Sham-ischemic animals were treated with vehicle. Each group consisted of 10 pregnant rats. We measured placental mitochondrial respiratory control index (RCI; a marker of mitochondrial respiratory activity), the ratio of the added adenosine 5-diphosphate (ADP) concentration to consumption of oxygen during state 3 respiration (ADP/O), and the concentration of thiobarbituric acid reactive substances (TBARS) in each group. RCI and ADP/O were significantly decreased by ischemia/reperfusion, while TBARS were increased. Melatonin prevented these changes. These results indicate that exogenous melatonin protects against ischemia/reperfusion-induced oxidative damage to mitochondria in rat placenta. Melatonin could be useful in treating preeclampsia and possibly other clinical states involving excess free radical production, such as fetal growth restriction and fetal hypoxia.

Melatonin administration prevents cardiac and diaphragmatic mitochondrial oxidative damage in senescence-accelerated mice

“…Also in vivo, acute administration of aMT protected diaphragmatic and skeletal muscle mitochondria from oxidative/nitrosative damage (Escames et al 2006, Lopez et al 2006b), improving the ability of these mitochondria to produce ATP (Lopez et al 2006a). In SAM mice, aMT administration counteracted mitochondrial deficiencies (Okatani et al 2001(Okatani et al , 2002a. Recently, an inverse relationship was demonstrated between the reduction in aMT content and the increased oxidative damage in several tissues of SAM mice including liver, spleen and thymus (Lardone et al 2006).…”

Melatonin ameliorates renal ischemia/reperfusion injury

“…Melatonin reduces lipid peroxidation and protects against I/R injury through its radical-scavenging action [13][14][15][16][17]. It is nontoxic, rapidly absorbed from any tissue, and diffuses easily through interstitial and cell compartments alike.…”

Improved mitochondrial function and increased life span after chronic melatonin treatment in senescent prone mice

“…Several studies have reported that acute aMT administration, an antioxidant and free radical scavenger (Antolin et al, 1996;Tan et al, 2000aTan et al, , 2000bTan et al, , 2002Turjanski et al, 2001), counteracted mitochondrial deficiencies in SAM mice (Okatani et al, 2001(Okatani et al, , 2002a(Okatani et al, , 2002b. The indoleamine and several of its metabolites are scavengers of free radicals and it is now considered a component of the endogenous antioxidant system (Reiter, 1998(Reiter, , 2000Tan et a., 2007).…”