Effects of Salts and Adrenal Cortical Extracts upon Toxicity of Drugs

Abstract

Verzar and his coworkers 1 in discussing the possible relationships between the adrenal cortex and fat, carbohydrate, and electrolyte metabolism, have postulated that the adrenal cortex controls a wide number of metabolic processes by regulating phosphorylation processes.

One of the primary arguments of these workers is that the effects of iodoacetate poisoning seemed to reproduce some of the symptoms of adrenal insufficiency, such as impaired selective intestinal absorption of glucose, muscular asthenia, steatorrhea, lowered body temperature, fluid loss by diarrhea, etc. These effects are ascribed to a specific inhibitory action of iodoacetate upon phosphorylation.

Laszt 2 has found that NaCl therapy antagonizes the iodoacetate effects in the intact rat, with respect to fatal toxicity, and impaired intestinal glucose absorption. This observation was offered as a possible explanation of some of the beneficial effects of NaCl therapy in adrenal insufficiency.

It appeared possible that this so-called “experimental adrenal insufficiency” produced by iodoacetate, could be explained on another basis than by specific inhibition of phosphorylations. This possibility was brought to our attention by the well known efficacy of NaCl, base, and fluid therapy in many toxic conditions, such as in mercury poisoning, 3 in which fluids are lost by emesis and diarrhea, and uremia ensues as a result of kidney damage. Such toxic agents could not be expected specifically to inhibit phosphorylations under the control of the adrenal cortex, although some of them may produce changes which have been termed symptoms of the “alarm reaction” by Selye and his coworkers. 4 For this reason, we have investigated the effects of NaCl, KC1, fluids, and adrenal cortical hormone upon rats poisoned with several non-specific toxic agents, including iodo-acetate.

Four groups of 18 rats each were divided into 2 subgroups averaging ca 150 g per rat, each group receiving subcutaneously 50 and 80 mg per kg of sodium iodoacetate, respectively.