The multiple biological action potential of melatonin – is melatonin, mitochondria and the ischemic/reperfusion injury relationship essential in the pathogenesis of obstructive nephropathy?

Melatonin is known to have a multiple biological action potential. Melatonin and several of its metabolites have been shown to act as an antioxidant and cytoprotective agent by reducing the oxidative stress by acting as a free radical scavenger [1], and also by activating several antioxidant systems [2]. Melatonin is originally defined as an agent which reduces lipid peroxidation and scavenges reactive oxygen species which usually initiate lipid peroxidation [3]. Furthermore , melatonin has potent antioxidant properties [4]. Melatonin stimulates antioxidant enzymes (e.g. glutathione peroxidase, glutathione reductase, etc.) and suppresses oxidative enzymes (lipoxygenase and nitric oxide synthase). It is believed that melatonin can protect the mitochondria and exert strong anti-apoptotic effects [5]. In a current study, Yildirim et al. showed that melatonin significantly reduces the apoptotic scores occurring after acute unilateral ureteral obstruction in a kidney rat model [6]. However, the authors did not observe a return to normal histological features in the obstructed kidneys. In general, obstructive uropathy leads to tubular damage (atrophy) due to apoptosis induction. Impaired urine flow can cause increased accumulation of reactive oxygen species and environmental changes favoring pro-apoptotic factors within the kidney. A wide range of intrarenal factors can stimulate intense fibrosis. Progressive fibrosis with overproduction of extracellular matrix proteins (e.g. collagen, fibronectin, etc.) is a key process in kidney function deterioration. These proteins are accumulated in the tubulointerstitium leading to further renal impairment. Urethral obstruction affects proper The multiple biological action potential of melatonin – is melatonin, mitochondria and the ischemic /reperfusion injury relationship essential in the pathogenesis of obstructive nephropathy?