Protective role of melatonin and retinol palmitate in oxidative stress and hyperlipidemic nephropathy induced by adriamycin in rats.
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.
Montilla
P L
PL
Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad de Córdoba, Spain.
Túnez
I F
IF
Muñoz de Agueda
C
C
Gascón
F L
FL
Soria
J V
JV
D000818:Animals; D004224:Diterpenes; D004317:Doxorubicin; D005978:Glutathione / Q000378:metabolism; D006949:Hyperlipidemias / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007674:Kidney Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control; D050356:Lipid Metabolism; D008054:Lipid Peroxides / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008550:Melatonin / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D011507:Proteinuria / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar; D000084562:Retinyl Esters; D014801:Vitamin A / Q000031:analogs & derivatives* / Q000494:pharmacology
D004224:Diterpenes; D008054:Lipid Peroxides; D000084562:Retinyl Esters; D014801:Vitamin A; C014794:retinol palmitate; D008315:Malondialdehyde; D004317:Doxorubicin; D005978:Glutathione; D008550:Melatonin