Studies on thromboxane B2 and prostaglandin E2 production in the course of murine autoimmune disease: inhibition by oral histidine and zinc supplementation.
Synthesis of both prostaglandin E2 and thromboxane B2 in liver and kidney tissue of NZB/W F1 hybrid mice was found to increase with advancing age. The rise in prostanoid generation coincided with the appearance and progression of the spontaneous systemic lupus erythematosus (SLE)-like disorders seen in these mice. Substitution of a diet supplemented with histidine (50 g kg-1 dry weight) and/or zinc (160 mg kg-1 dry weight) suppressed the autoimmune disease associated increase in prostanoid generation. The parent NZB and NZW strains also revealed an age-dependent increase in prostanoid synthesis whereas no age-related changes of tissue prostanoid generation were seen in healthy DBA-2 and C57-BL/6 control mice. In a previous study [Schwerdtfeger et al. 1980] a protective effect of histidine and/or zinc on the course of SLE-like disease in NZB/W F1 mice was reported. The current work suggests that this effect may in part have been mediated by the modulation of cellular arachidonic acid metabolism. The proposal that prostanoids are involved in the pathogenesis of autoimmune disease in NZB/W F1 mice is supported by these results.
D000284:Administration, Oral; D000367:Age Factors; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D001327:Autoimmune Diseases / Q000517:prevention & control*; D004032:Diet; D015232:Dinoprostone; D005260:Female; D006639:Histidine / Q000008:administration & dosage / Q000627:therapeutic use*; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D011458:Prostaglandins E / Q000096:biosynthesis*; D013929:Thromboxane B2 / Q000096:biosynthesis*; D015032:Zinc / Q000627:therapeutic use*
D001095:Arachidonic Acids; D011458:Prostaglandins E; D006639:Histidine; D013929:Thromboxane B2; D015032:Zinc; D015232:Dinoprostone