Increased Stool Mercury Excretion in the Rat: The Effect of Spironolactone 1

Abstract

Selye has presented evidence that spironolactone pretreatment protects the rat against a variety of toxins including digitoxin (1), anesthetics (2), indomethacin (3), and mercury (4). Spironolactone pretreatment for 4 days protects rats both from renal damage and from death which would otherwise result from iv HgCl₂. If spironolactone treatment is initiated after iv HgCl₂ administration, no protective effect is demonstrable. The mechanism of spironalactone prophylaxis is unknown, although Seyle has suggested several possible explanations (4). The present experiments were undertaken in an effort to elucidate spironolactone's protective effect by tracing the fate of injected ²⁰³HgCl₂ in intact and adrenalectomized control animals and in intact and adrenalectomized animals pretreated with spironolactone.

Materials and Methods. Experiment No. 1—Intact animals. Twenty-seven male Sprague-Dawley rats with a mean body weight of 110 g were divided into two groups. Group 1 animals were maintained on standard laboratory chow and tap water and served as controls. Group 2 animals were maintained similarly and were given 10 mg spironolactone in 2 ml water twice daily by gavage throughout the experiment. On the fourth day both groups of animals received a single iv dose of 400 μg HgCl₂ in 0.5 ml isotonic saline which also contained 1.5 μCi of ²⁰³HgCl₂. The amount of radioactivity administered was calculated from the weight difference of the administering syringe before and after injecting, and a similarly weighed sample was saved for standardization of gamma well counting. Nine Group 1 animals and eight Group 2 animals were placed in metabolic cages and were sacrificed with ether at the end of 24 hr. An additional three Group 2 animals (two in metabolic cages) and an additional four Group 1 animals (two in metabolic cages) were kept as long as 48 hr before being sacrificed.