Melatonin ameliorates chronic renal failure‐induced oxidative organ damage in rats

Abstract

Chronic renal failure (CRF) is associated with oxidative stress that promotes production of reactive oxygen species (ROS). Melatonin, the chief secretory product of the pineal gland, was recently found to be a potent free radical scavenger and antioxidant. The aim of this study was to examine the role of melatonin in protecting the aorta, heart, corpus cavernosum, lung, diaphragm, and kidney tissues against oxidative damage in a rat model of CRF, which was induced by five of six nephrectomy. Male Wistar albino rats were randomly assigned to either the CRF group or the sham-operated control group, which had received saline or melatonin (10 mg/kg, i.p.) for 4 wk. CRF was evaluated by serum blood urea nitrogen (BUN) level and creatinine measurements. Aorta and corporeal tissues were used for contractility studies, or stored along with heart, lung, diaphragm, and kidney tissues for the measurement of malondialdehyde (MDA, an index of lipid peroxidation), protein carbonylation (PC, an index for protein oxidation), and glutathione (GSH) levels (a key antioxidant). Plasma MDA, PC, and GSH levels and erythrocytic superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities were studied to evaluate the changes of antioxidant status in CRF. In the CRF group, the contraction and the relaxation of aorta and corpus cavernosum samples decreased significantly compared with controls (P < 0.05-0.001). Melatonin treatment of the CRF group restored these responses. In the CRF group, there were significant increases in tissue MDA and PC levels in all tissues with marked reductions in GSH levels compared with controls (P < 0.05-0.001). In the plasma, while MDA and PC levels increased, GSH, SOD, CAT, and GSH-Px activities were reduced. Melatonin treatment reversed these effects as well. In this study, the increase in MDA and PC levels and the concomitant decrease in GSH levels of tissues and plasma and also SOD, CAT, GSH-Px activities of plasma demonstrate the role of oxidative mechanisms in CRF-induced tissue damage, and melatonin, via its free radical scavenging and antioxidant properties, ameliorates oxidative organ injury. CRF-induced dysfunction of the aorta and corpus cavernosum of rats was reversed by melatonin treatment. Thus, supplementing CRF patients with adjuvant therapy of melatonin may have some benefit.

Estrogen Protects against Oxidative Multiorgan Damage in Rats with Chronic Renal Failure

“…Apart from the major enzymatic antioxidants, such as superoxide dismutase, GSH peroxidase, and catalase, estrogens are also classified as nonenzymatic antioxidants that delay or inhibit age-associated pathological and biological changes. [57] Several experimental studies have shown that antioxidant capacity of tissues is decreased in animals with CRF, [58,59] while marked reductions in plasma glutathione concentration and glutathione peroxidase activity, as well as marked increases in the ratios of oxidized to reduced GSH were observed in CRF patients. [60,61] Current findings show that the reduction in GSH content of the studied tissues of male and ovariectomized rats may be due to its consumption during CRF-induced oxidative stress.…”

Lipid peroxidation in liver tissue of ovariectomized and pinealectomized rats: effect of estradiol and progesterone supplementation

“…12 It was established that formation of free radicals, which were induced by several stimuli in renal tissue was prevented by melatonin. 13,14 Likewise, it is indicated that as a result of pinealectomy to remove the main source of melatonin, increases of lipid peroxidation in tissues occurs.…”

Factors Those Up Regulate <i>Klotho</i> and Glutathione Peroxidase-1 Gene Expression Improve Renal Function in Rats with Acute Renal Failure

“…These results also are in a harmony with the recorded data by Macdonald et al (2003) explained the oxidative stress occurs when a balance is disrupted by excessive production of Reactive Oxygen Speacies (ROS), including superoxide, hydrogen peroxide and hydroxyl radicals and/or by inadequate antioxidant defenses, including suboptimal levels of catalase, Glutathione Peroxidase (GPx), vitamins C and E and reduced glutathion. Sener et al (2004) found that in the erythrocytes of male Wistar albino rats at 4 weeks after 5/6 nephrectomy, GPx activity was found to be reduced, in addition Devinder et al (2004) found that the glycerol treated group showed depletion in antioxidant system which indicated by the significant decrease in the levels of glutathione reductase and superoxide dismutase enzymes. Pandir and Kara (2013) clarified that Superoxide Dismutase (SOD), catalase (CAT) and Glutathione Peroxidase (GPx) activities were decreased and malondialdehyde MDA levels were increased in the cisplatin nephrotoxicity group.…”