The effect of omega-3 fatty acids and vitamin E on the nephrotoxicity of cyclosporin A in hereditary hypertriglyceridemic rats

It has been suggested that cyclosporin A (CsA) nephrotoxicity can be reduce d by the concomitant administration of omega-3 fatty acids or vitamin E. Th e present study was designed to establish whether the effect of the above s ubstances can also be demonstrated in rats with hereditary hypertriglycerid emia (HTG) whose sensitivity to the nephrotoxic effect is greater than in c ontrol AVN rats. CsA administration at a dose of 10 mg/kg/day to HTG rats r esulted in a significant rise (p<0.001) in serum levels of creatinine (from 66.0+/-7.6 to 108.4+/-11.6 mu mol/l) and urea (from 8.3+/-0.7 to 22.3+/-18 mmol/l) which was not found in AVN rats. The baseline values of systolic b lood pressure (SBP) were significantly higher in HTG rats. However, in both strains CsA administration was associated with a similar SEP increase whic h was not prevented by omega-3 fatty acids (EPAX) or vitamin E administrati on. Concomitant administration of CsA with EPAX at a dose of 600 mg/kg b.w. /day in HTG rats prevented the rise in the serum levels of creatinine (65.4 +/-14.7 mu mol/l) and reduced the increase in the serum urea levels (11.9+/ -7.6 mmol/l). Concomitant administration of CsA and vitamin E (at a dose of 25 mg/kg/day) also reduced the increase (p<0.05) in the serum levels of cr eatinine (70.7+/-14.3 mu mol/l) and urea (9.8+/-3.4 mmol/l) compared to the effects elicited by the administration of CsA alone (p<0.05). Administrati on of CsA alone or in combination with EPAX or vitamin E did not have a mar ked effect on diuresis, proteinuria, urinary osmolality, urinary excretion of urea, creatinine and potassium. Under all experimental conditions, the r ate of urinary excretion of sodium in HTG rats was significantly lower (p<0 .01) than in AVN rats. The results obtained support the assumption that ome ga-3 fatty acids and vitamin E at the doses used reduce CsA nephrotoxicity in rats with hereditary hypertriglyceridemia whose sensitivity to the nephr otoxic effect of CsA is significantly higher than in AVN rats.