Role of free radicale in the development of pneumocyte proliferation

Abstract

Nutrients rich in omega-3 fatty acids (fish oil and flaxseed) have the potential to abrogate inflammatory and atherosclerotic mechanisms known to be involved in the pathogenesis of vascular damage of systemic lupus erythematosus nephritis. Fish oil dietary supplementation decreases proteinuria and preserves renal morphology in the NZB/NZW, BXSB, and MRL/lpr mouse models of lupus nephritis and decreases mortality in the NZB/NZW and BXSB models. The anti-inflammatory and anti-atherosclerotic potential, coupled with the animal experimental data, encouraged us to carry out a dosing study of low (6 g) and higher (18 g) doses of fish oil (MaxEPA) therapy in human lupus nephritis. At the lower dose, the fish oil inhibited inflammatory mechanisms; at the higher dose, it aHered both the inflammatory and atherosclerotic mechanisms. This led to a double-blind cross-over study of fish oil therapy in 26 patients with lupus nephritis followed for 2 years 10 weeks. The fish oil dietary supplementation had no significant effect on proteinuria, isotope glomerular filtration rate, disease activity index, or steroid consumption. However, it did have a significant effect on lipid levels. The cross-over design suffered carryover effects (even with a 10-week wash-out period) and placebo effects of the olive oil, which created a risk of type II error. Our interest in omega-3 fatty acids led us to assess the effects of dietary supplementation with flaxseed. Not only is the flaxseed a major source of alpha-linolenic acid but it is also the richest natural source of lignan, a natural plateletactivating factor receptor antagonist. The 15% flaxseed dietary supplementation in the MRL/lpr mouse model resulted in a significant preservation in glomerular fiHration rate, a delay in proteinuria, and abrogation of lymphoproliferation. In addition, unlike MaxEPA, the flaxseed dietary supplementation resuHed in a significant 60% reduction in mortality. We concluded that, at present, fish oil is not indicated as a form of treatment in patients with lupus nephritis, but flaxseed dietary supplementation warrants further study.