Effects of fish oil and sunflower oil supplementations on gentamicin-induced nephrotoxicity in rat

Abstract

1 Nephrotoxicity was induced in rats by intramuscular administration of gentamicin (80 mg kg^-1 d^-1) for 6 days.

2 Oral supplementation with fish oil (5 ml kg^-1 d^-1), for 2 weeks prior to and during gentamicin exposure, markedly ameliorated the drug-induced nephrotoxici ty. The beneficial effects of oil were evidenced by sig nificantly reduced serum creatinine and urea concen trations, increased renal cortical alkaline phosphatase activity and improved renal tubular histology, com pared with the non oil-treated animals, receiving gen tamicin.

3 Similar supplementation with sunflower oil, rich in ω-6 fatty acids, failed to reverse any of the parameters of nephrotoxicity induced by gentamicin.

4 Hypercholesterolaemia and reduced cortical GSH associated with gentamicin nephrotoxicity were both normalised by supplementation with fish oil, but not by sunflower oil.

5 The beneficial effects of fish oil on gentamicin-induced nephrotoxicity were not related to the extent of uptake and accumulation of the drug by the kidney.

Keywords

fish oil sunflower oil gentamicin aminoglyco sides nephrotoxicity rat

Get full access to this article

View all access options for this article.

References

Lee SM , Pattison ME , Michael UF Nitrendipine protects against aminoglycoside nephrotoxicity in the rat. J Cardiovasc Pharmacol 1987; 9 suppl 1: S65-S69.

Wise WJ et al. Fish oil has protective and therapeutic effects on proteinuria in passive Heymann nephritis. Kidn Internat 1993; 43: 359-368.

Stahl Rak et al. Enhanced glomerular prostaglandin formation in experimental membrane nephropathy. Kidn Internat 1987; 31: 1126-1131.

Cybulsky AV et al. A role of thromboxane in complement mediated glomerular injury . Am J Pathol 1987; 128: 45-51.

Sedlak JI , Lindsay RH

Estimation of total protein bound and non protein bound sulfhydryl groups in tissues with Ellman's reagent. Analyt

Biochem 1968; 25: 192-200.

Belfield A. , Goldberg DM Revised assay for serum phenylphosphatase activity using 4-amino antipyrine . Enzyme 1971; 12: 561-573.

Lowry OH et al. Protein measurement with Folin phenol reagent. JBiol Chem 1951; 193: 265-275.

Fukuda Y. , Eklof AC , Malmborg AS , Aperia A. Calcium supplementation and thyroid hormone protect against gentamicin-induced inhibition of tubular Na+ K+-ATPase activity and other renal functional changes . Acta Physiol Scand 1992; 145: 93-98.

Clark WF et al. Fish oil in Lupus nephritis: clinical findings and methodological implications. Kidn Internat 1993; 44: 75-86.

10.

Kelley VE , Ferrctti A. , Izui S. , Strom TB A fish oil diet rich in eicosapentaenoic acid reduces cyclooxygenase metabolites and suppresses lupus in MRL-Lpr mice. J Immunol 1985; 134: 1914-1919.

11.

Papanikolaou N. et al. Does gentamicin induce renal failure by increasing renal TXA2 synthesis in rats? Prostaglandins leukotrienes . Essential Fatty Acids 1992; 45: 131-136.

12.

Bennett WM et al Effect of sodium intake on gentamicin nephrotoxicity in the rat . Proc Soc Exp Biol Med 1976; 151: 736-738.

13.

Whiting PH et al. The effect of dietary protein restriction on high dose gentamicin nephrotoxicity in rats. BrJExp Pathol 1988 ; 69: 35-41.

14.

Williams PD , Hottendorf GH , Bennett DB Inhibition of renal membrane binding of aminoglycosides . J Pharmacol Exp Therapeut 1986; 237: 919-925.

15.

Abdel-Gayoum AA , Ali BH , Ghawarsha K. , Bashir AA Plasma lipid profile in rats with gentamicin induced nephrotoxicity. Hum Exp Toxicol 1993 ; 12: 371-375.

16.

Connor WE , Lin DS , Harris WS A comparison of dietary Polyunsaturated ω-6 and ω-3 fatty acids in humans: effects upon plasma lipids, lipoproteins and steroid balance . Arteriosclerosis 1981; 1: 363a (Abstract).

17.

Illingworth DR , Harris WS , Connor WE Inhibition of low density lipoprotein synthesis by dietary ω-3 fatty acids in humans. Arteriosclerosis 1984; 4: 270-275.

18.

Harris WS Fish oil and plasma lipid and lipoprotein metabolism in humans. J Lipid Res 1989; 30: 785-807.

19.

Hirano T. , Morohoshi T. Treatment of hyperlipidaemia with probucol suppresses the development of focal and segmental glomerulosclerosis in chronic aminoglycoside nephrosis . Nephron 1992; 60: 443-447.

20.

Kacew S. Cationic amphiphilic drug-induced renal cortical lysosomal phospholipidosis: An in vivo comparative study with gentamicin and chlorphentermine. Toxicol Appl Pharmacol 1987; 91: 469-476.

21.

Ramsammy LS et al. Failure of inhibition of lipid peroxidation by vitamin E to protect against gentamicin nephrotoxicity in the rat. Biochem Pharmacol 1987; 36: 2125-2132.