A novel treatment for lupus nephritis: lignan precursor derived from flax.
BACKGROUND
Flaxseed has renoprotective effects in animal and human lupus nephritis. We have recently extracted the lignan precursor (secoisolariresinol diglucoside) (SDG) to determine if this more palatable derivative of flaxseed would exert renoprotection similar to the whole flaxseed in the aggressive MRL/lpr lupus mouse model.


METHODS
131 MRL/lpr mice were randomly assigned to saline gavage, 600, 1,200 and 4,800 microg lignan gavage groups. At 7 weeks, 6 animals underwent platelet aggregating factor (PAF) lethal challenge and 40 were studied with urine 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 1200 microg lignan groups were studied at 14 and 22 weeks for GFR, spleen lymphocyte S-phase and organ weight studies.


RESULTS
Metabolic studies indicated that secoisolariresinol is the major metabolite absorbed and the lowest lignan dose provides a lengthening in survival for the PAF lethal challenge. Body weight, fluid and water intake studies demonstrated that the lignan was well tolerated. Changes in proteinuria, GFR and renal size showed a time- and dose-dependent protection for the lignan precursor. Cervical lymph node size and spleen lymphocyte cells in the S-phase demonstrated modest dose-dependent reductions in the lignan gavaged groups.


CONCLUSIONS
SDG was converted in the gut to secoisolariresinol, which was absorbed and well tolerated by the MRL/lpr mice. Renoprotection was evidenced, in a dose-dependent fashion, by a significant delay in the onset of proteinuria with preservation in GFR and renal size. This study suggests that SDG may have a therapeutic role in lupus nephritis.
Clark
W F
WF
Department of Medicine, London Health Sciences Centre and The University of Western Ontario, Canada. william.clark@lhsc.on.ca
Muir
A D
AD
Westcott
N D
ND
Parbtani
A
A
D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000652:urine; D000818:Animals; D001779:Blood Coagulation Factors / Q000378:metabolism; D019597:Flax / Q000627:therapeutic use*; D006801:Humans; D017705:Lignans / Q000627:therapeutic use* / Q000652:urine; D008181:Lupus Nephritis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D008517:Phytotherapy; D010972:Platelet Activating Factor; D012639:Seeds
D001779:Blood Coagulation Factors; D017705:Lignans; D010972:Platelet Activating Factor; C029498:2,3-bis(3'-hydroxybenzyl)butane-1,4-diol; D015107:4-Butyrolactone; C029497:2,3-bis(3'-hydroxybenzyl)butyrolactone