Observations on Hexachlorophene-Induced Paralysis in the Cat and Its Antagonism by Hypertonic Urea

Abstract

The toxic effects of hexachlorophene (HCP) on the central nervous system include paralysis of limbs with tonic extensor rigidity and edema and spongy degeneration of white matter in the brain and spinal cord (1 -4). These effects are reversible upon cessation of HCP administration (2), making it unlikely that permanent damage to cerebrospinal neurons is sustained in surviving animals. Instead, the signs suggest a "pressure lesion" ( 5 ) with the possibility of fatal outcome in cases that are severe, sustained, and unrelieved. This led us to investigate whether toxic amounts of HCP produce elevations of cerebrospinal fluid pressure (CSFP) and if so, whether this effect could be antagonized or reversed. The wide range of neurological observations accessible to simple "clinical" test in the cat was the basis for choice of this species over the rat for studies reported here.Materials and methods. Eighteen male mongrel cats, 1 to 2 years old, were immunized for distemper and pneumonitis and allowed to become accustomed to our laboratory for 4 to 5 weeks before use. They were removed from their cages twice each week and allowed free movement in the animal room while under observation to accustom them to the handling necessary for dosing and examination. They were systematically observed before and after treatment according to a checklist that included the criteria from Norton and DeBeer ( 6 ) , including recognition of personnel, grooming, feeding, drinking, and exploratory behavior, and many of the neurological tests outlined by McGrath (7), such as muscle tone, stretch, righting, placing, and extensor and pinnal reflexes.HCP, at a dose of 20 mg/kg, was weighed into a capsule for each animal and administered daily by the oral route. Blood samples 165

Deviations in hepatic amino acid profiles of mouse following repeated hexachlorophene administration

“…The ammonia is a potent neurotoxin which can be implicated in the clinical expression of neurologic symptoms in HCP intoxication. The amino acid perturbations reported in this study alongwith other findings such as depleted skeletal muscle mass (Hanig et al, 1976), abnormal amino acid turnover by the skeletal muscle {Prasad et al, 1987c) are consistent with the hypothesis that the liver -skeletal muscle metabolic interrelations which are important in the maintenance of nitrogen homeostasis (Banks et al, 1976) appear to be seriously disturbed in HCP intoxication.…”

“…The liver weight reduction was lesser as compared to the total body weight loss and the liver somatic index was significantly increased in HCP administered mice (Table 1). An important factor that contributes to the body weight reduction in HCP intoxication could be the rapid loss of skeletal muscle mass (Hanig et al, 1976). In a more recent study we have demonstrated a progressive depletion of hepatic glycogen and protein in mice given 60 mg HCP/kg/day for 7 consecutive days (Prasad et al, 1987a).…”