Protective role of melatonin and retinol palmitate in oxidative stress and hyperlipidemic nephropathy induced by adriamycin in rats

Abstract

We have studied the effects of melatonin and retinol palmitate (RP) on the nephropathy and oxidative stress induced by a single and high dose of adriamycin (AD) in Wistar male rats. A dose of melatonin (75 microg/kg/day) and a dose of RP (0.25 g oily solution/kg/day, s.c.) were injected 3 and 9 days before and after the administration of AD (25 mg/kg, i.p.), respectively. After the decapitation, samples were taken from the neck vascular trunk in order to determine the triglycerides, total cholesterol, phospholipids, HDL-cholesterol, total proteins, urea, lipoperoxides, and reduced glutathione (GSH). We estimated the lipoperoxide and glutathione (GSH) contents in renal homogenates, and the excretion of proteins in urine over a 24 hr period. The administration of AD caused significant increases in proteinuria and in the other parameters studied [lipids (triglycerides, total cholesterol, phospholipids, and HDL-cholesterol), non-protein nitrogen compounds, and lipoperoxides]. AD increased the lipoperoxide content, but it decreased the GSH content in the kidney. Both melatonin and RP, although melatonin more significantly, decreased the intensity of the changes produced by the administration of AD alone. In fact, melatonin was quite efficient in reducing the formation of lipoperoxides, restoring renal GSH content and decreasing remarkably the severity of proteinuria. These results support the powerful antioxidant action of melatonin at renal level and a lower antioxidant action of retinol. Likewise, these data reinforce the hypothesis which supports the pathogenetic role and the close relation between the oxidative stress and the expression of the nephropathy induced by AD. However, in spite of this obvious antioxidant effect of melatonin in the kidney, additional studies are required to establish accurately the role of this pineal indole in the regulation and dynamics of the antioxidative defense enzyme system, which neutralizes the damaging effect of free radicals, both endogenous and exogenous, in this organ.

Effect of melatonin on hyperlipidemic nephropathy under constant light exposure

“…These studies showed that melatonin lowered triglycerides, phospholipids and total cholesterol levels and increased HDL-c levels in experimental hyperlipidemia induced by adriamycin (10,11), findings confirmed by the present study. We have also observed that melatonin is more effective in hyperlipidemia than vitamin E (10). In the present study we confirmed the melatonin effect on the levels of LDL-c, HDL-c and total cholesterol, data that indicate an action both endogenous and exogenous melatonin on J. Physio!.…”

“…Many studies support the beneficial and protective effects of antioxidants in these pathologies (9,16). Melatonin, in accord with research carried out by our group, significantly reduces the intensity of oxidative stress, hyperlipidemic and signs of renal disruption induced by adriamycin in rat (10,11).…”

Antioxidants: A Possible Role in Kidney Protection

“…Supplementation of MLT is capable of decreasing an oxidative stress at renal tissues and attenuate kidney scaring (table 3) [117][118][119][120][121][122][123][124][125][126][127][128][129][130][131]. Additionally, MLT decreases serum lipid levels [132,133].…”

The Oxidant/Antioxidant Network: Role of Melatonin

“…Some of the organs in which these protective effects have been shown include the gastrointestinal tract and adnexa [25,[39][40][41][42], central nervous system [2,[43][44][45][46][47], eye [48,49], kidneys [42,50], heart [51,52], blood elements [27,53], lungs [54] and muscle [55]. The macromolecules that have been most often studied in terms of the protective actions of melatonin include lipids [6, 25-27, 36-38, 42, 48, 49, 54-56] and nuclear DNA [6, 10, 36-38, 53, 57, 58].…”