Hyperlipidemic Nephropathy Induced by Adriamycin: Effect of Melatonin Administration

Abstract

The effect of melatonin (MEL) on the nephropathy and the oxidative stress induced by a single and high dose of Adriamycin (AD) has been studied in Wistar male rats. MEL (50 μg/kg/day) was injected intraperitoneally 3 and 7 days, respectively, before and after AD injection (20 mg/kg i.p.). Trunk blood was drawn and triglycerides, total cholesterol, phospholipids, high-density lipoprotein cholesterol, urea, creatinine, total protein, lipoperoxides, and reduced glutathione (GSH) levels and catalase activity (CAT) were determined in serum. In kidney homogenates, lipoperoxides, GSH, and CAT were measured as well as total protein in urine. AD administration resulted in hyperlipidemia and high-grade proteinuria and a marked increase in serum lipoperoxides, urea, and creatinine. In the kidney, the increase in lipoperoxides was accompanied by a significant decrease of GSH and CAT. The efficiency of MEL was specially remarkable in restoring GSH, CAT, and proteinuria to the levels of controls. These results confirm the involvement of free radicals in the pathogenesis of nephrotoxicity induced by AD. Likewise, they show the high antioxidative power of MEL and its marked effect on the prevention and suppression of this nephropathy.

A novel approach to contrast-induced nephrotoxicity: the melatonergic agent agomelatine

“…35 Another important inflammatory cytokine, IL-6, exhibits many physiological effects. 36 Contrast media administration was shown to lead to an increase in the levels of IL-6 in the kidney, 38 while TNF-a led to an increase in NF-kB. 51,52 In our study, NF-kB upregulation, in parallel with contrast media and glycerol administration, correlated with the increasing levels of TNF-a and IL-6.…”

“…The latest literature states that melatonin averts nephrotoxicity triggered by several drugs. [33][34][35][36][37][38] In particular, Gazi et al 39 demonstrated the defensive effect of melatonin administration in rat radiocontrast nephrotoxicity by reducing BUN and creatinine levels. 40 However, these studies have not measured oxidative and molecular parameters to indicate whether regeneration of the kidneys occurred after injury.…”

Melatonin, a Pineal Hormone with Antioxidant Property, Protects against Gentamicin-Induced Nephrotoxicity in Rats

“…Significant inhibition of MDA in both plasma and kidney tissue by melatonin may be due to its antioxidant effect. In serum and kidney tissue, melatonin significantly reverted the Adriamycin-induced increase in lipid peroxide [23]. Simultaneous administration of melatonin also significantly reduced lipid peroxidation induced by paraquat, bacterial lipopolysaccharide, and hydrogen peroxide [47].…”

“…In rats, melatonin, through its antioxidant properties, protected the animals from Adriamycin-induced nephropathy [23]and cardiomyopathy [24]. The antioxidant action of melatonin is also supported by results of experiments showing that it decreases the DNA damage caused by ionizing radiation in cultured cells [25]and by safrole in experimental animals [26]and that it also protects cells, tissues, and organs against oxidative damage caused by paraquat [27], lipopolysaccharide [28], glutathione depletion [29], and ischemic reperfusion [30].…”

Hyperlipidemic Nephropathy Induced by Adriamycin in Ovariectomized Rats: Role of Free Radicals and Effect of 17-Beta-Estradiol Administration

“…The oxidative status is particularly relevant in renal tissue where a highly regulated antioxidant enzyme system has been demonstrated [23]. Furthermore, the administration of antioxidants (β-carotene, α-tocopherol and melatonin) and superoxide dismutase significantly decrease the biochemical parameters of the oxidative stress observed in AD-induced nephropathy, especially proteinuria [24, 25, 26]. …”