Superoxide Anion in Polymorphonuclear Leukocytes of Hairless Rats Suffering from Magnesium‐deficiency Dermatitis

Abstract

Clinical and histological studies were made on magnesium-deficiency dermatitis produced on a new strain of hairless rats. Superoxide anion generation in polymorphonuclear leukocytes (PMNs) and the inhibitory effect of some antioxidants and anti-inflammatory agents against the elicited dermatitis were also examined. From the detection of increased superoxide production and effective actions of inhibitors including superoxide dismutase, cepharanthine, 4-4'-diamono-diphenylsulphone and 5,4,11,14-eicosatetraynoic acid (ETYA), it is indicated that superoxide anion or related activated oxygen may be responsible for magnesium-deficiency dermatitis as an inflammatory mediator and that the dermatitis may be related to lipoxygenase metabolites derived from arachidonic acid.

Atopic dermatitis-like symptoms in hypomagnesaemic hairless rats are prevented and inhibited by systemic or topical SDZ ASM 981

“… 46 A role for free radicals in oxidative tissue damage during magnesium deficiency is suggested by the observation that treatment with various antioxidants is effective against the development of skin and myocardial lesions. 15 , 48–50 Here, we have shown that improvement of clinical signs by oral SDZ ASM 981 was accompanied by a reduction in serum NO. Whether this might be due to a direct inhibiting effect of SDZ ASM 981 on NO production is not known, but direct inhibition of NO production by cultured macrophages was shown for cyclosporin A and FK 506.…”

“…The appearance of skin changes was found to be associated with several systemic abnormalities including histaminaemia, degranulation of tissue mast cells, increased serum serotonin, leucocytosis, overproduction of nitric oxide (NO) and increased superoxide anion production. 9–15 Further findings in magnesium‐deficient rats or mice are lymphocyte hyporeactivity, hypoplasia of thymic and thymodependent areas, increased IgE levels, reductions in several classes of circulating immunoglobulins (IgM, IgG, specific antibodies) and changes in interleukin (IL)‐1, IL‐6 and tumour necrosis factor‐α. 16–23 Moreover, the clinical severity of skin changes coincides with eosinophil accumulation in the peripheral blood and lesional skin.…”

Diet‐induced dermatitis response of hairless rats to systemic treatment with cyclosporin A (Sandimmun®), cyclosporin H and FK506

“…18) in which reports on pruritus are conttadictory. Benureau et al, (11) as well as Bois et al (19) reported a progressive skin reddening aecompanied by seratching while no signs of pruritus were observed by other investigators (12)(13)(14)(15)20). These divergent observations may be due to variations in diets and the respective sources and ages of the rats.…”

“…Histaminetnia is probably an indieator of tnast eell aetivation and other mast eell produets involved. Inhibitors of prostaglandin biosynthesis sueh as aeetylsalieylie aeid, indomethaein, piroxieatn or fiurbiprofen also failed to suppress the skin manifestations (13,14,20). Benoxaprofen and ETYA (5, 8, 11, 14-eieosatetraynoic acid), inhibitors of both cyclo-oxygetiase and lipoxygenase pathways, only slightly tnodified the developtnent of the dermatosis at relatively high doses (13,20).…”

The hypomagnesic rat model: dermatitis‐prone hairless rats with mild magnesium depletion fed a diet low in lipids did not develop pruritic dermatitis

“…The rash is because of lowered serum Mg 2+ and is described in the literature as extremely pruritic (3). The mechanism(s) by which hypomagnesaemia in hairless rats can lead to eczematous skin lesions may involve mediators in the lipid metabolism, presumably leukotriene B 4 (4, 5). The dermatitis can be relieved by giving magnesium to the rats (6, 7), by antagonising the leukotriene B 4 receptor (4) and by suppressing the immune system (8, 9).…”