Effect of dietary fish oil supplementation on eicosanoid production by rat renal allografts

Abstract

Acute renal allograft rejection is associated with significant alterations in renal arachidonic acid (AA) metabolism including increased production of the vasoconstrictor eicosanoid thromboxane (TX)A2. TX synthetase inhibition improves function of rejecting rat renal allografts but is difficult to accomplish pharmacologically. Therefore, we evaluated the potential use of dietary fish oil (FO) as a more practical method for reducing renal thromboxane production. We examined the effects of dietary FO supplementation on eicosanoid production and hemodynamic function of rat renal allografts. Donor and recipient rats were fed a fat-free diet supplemented with beef tallow (BT) or FO. After 6 weeks on the experimental diet, kidneys from ACI donors were transplanted into PVG recipients. Six days after transplant, renal function and eicosanoid production were measured. FO feeding resulted in significant alterations in eicosanoid production by renal allografts. There was a marked and generalized reduction in prostaglandin (PG) and TX production by allografts when both donor and recipient were fed a diet supplemented with fish oil. An intermediate reduction in production of PGE2 (and perhaps PGI2), but not TXB2, was observed when only the recipient was fed FO. Feeding FO to the donor alone had no effect on renal PG or TX production. These data suggest that both donor and recipient fatty acid pools contribute to AA metabolism during rejection. Unlike specific TX inhibition, the generalized inhibition of AA metabolism that occurred with FO feeding was not associated with improvement in function or morphology of allografts. However, potential benefit at earlier stages or in milder forms of rejection is possible and was not evaluated.