A novel treatment for lupus nephritis: lignan precursor derived from flax

Background: Flaxseed has renoprotective effects in animal and human lupus n ephritis. We have recently extracted the lignan precursor (secoisolariresin ol diglucoside) (SDG) to determine if this more palatable derivative of fla xseed would exert renoprotection similar to the whole flaxseed in the aggre ssive MRL/lpr lupus mouse model. Methods: 131 MRL/lpr mice were randomly assigned to saline gavage, 600, 120 0 and 4800 mu g lignan gavage groups. At 7 weeks, 6 animals underwent plate let aggregating factor (PAF) lethal challenge and 40 were studied with urin e collection to determine the levels of secoisolariresinol, enterodiol and enterolactone in the gavaged animals. A baseline study of 10 saline gavaged animals took place at 6 weeks. 25 animals in the saline gavage, 600 and 12 00 mu g lignan groups were studied at 14 and 22 weeks for GFR, spleen lymph ocyte S-phase and organ weight studies. Results: Metabolic studies indicated that secoisolariresinol is the major m etabolite absorbed and the lowest lignan dose provides a lengthening in sur vival for the PAF lethal challenge. Body weight, fluid and water intake stu dies demonstrated that the lignan was well tolerated. Changes in proteinuri a, GFR and renal size showed a time- and dose-dependent protection for the lignan precursor. Cervical lymph node size and spleen lymphocyte cells in t he S-phase demonstrated modest dose-dependent reductions in the lignan gava ged groups. Conclusion: SDG was converted in the gut to secoisolariresinol, which was a bsorbed and well tolerated by the MRL/lpr mice. Renoprotection was evidence d, in a dose-dependent fashion, by a significant delay in the onset of prot einuria with preservation in GFR and renal size. This study suggests that S DG may have a therapeutic role in lupus nephritis.