Manganese and Hydralazine as Studied by Neutron Activation and Radioactive Mn

Abstract

Hydralazine produces a “Lupus-like” syndrome in a few patients. This syndrome has been reproduced experimentally in the laboratory, and, circumstantially, a Mn-deficiency seemed implicated. The results of a dietary deficiency of Mn were compared to the effects of hydralazine administration. The alterations produced by dietary Mn found in mice were not duplicated by hydralazine.

Studies relating hydralazine (“Apresoline,” CIBA) to manganese (Mn) metabolism have suggested that a Mn deficiency might be produced by long term administration of this drug(l). Because hydralazine can induce a syndrome similar to Systemic Lupus Erythematosus (SLE) in patients, it seemed possible that Mn deficiency might play a role in the etiology of this disease.

As neutron activation analysis (NAA) has proven to be a specific and accurate technique to measure tissue concentrations of Mn, it was used to determine whether hydralazine administration might lower Mn in tissues. Although tracer techniques are not a perfect answer to the study of physiologic disposition and metabolism of a biological material, the apparent identity of a compound and its radioisotope from a physiological point of view is widely accepted. Thus, kinetic studies utilizing ⁵⁴Mn were performed to determine whether hydralazine might induce functional deficiency of this trace metal.

The results of hydralazine administration were compared with the alterations of Mn induced by dietary manipulations of Mn. Tissue concentrations of Mn, whole body turnover rates of ⁵⁴Mn, and organ partition studies of ⁵⁴Mn responded readily to dietary alterations of Mn but not to hydralazine administration.

Male Swiss albino mice (BNL strain) were used throughout these studies. Effects of hydralazine on tissue levels of Mn were compared with effects of Mn-deficiency-inducing diet, as described by Hurley and associates (2). This diet contained 40 μg/g of Mn (unpublished data).