PHARMACOLOGICAL STUDY ON L-ORNITHINE L-ASPARTATE

Abstract

In a healthy subject, ammonia produced in the body is excreted by the kidney in the form of urea, the product of the urea cycle (1), or converted into substances useful for the body. In cases of hepatic disorders, on the other hand, blood ammonia level is known to increase (2-6). It is likely that ammonia in high concentrations interferes with the TCA cycle (7) and thus disturbs the completion of carbohydrate and protein metabolism so seriously as to cause inhibition of ATP synthesis and the subsequent liability or aggravation of fatty degeneration of the liver. It is also possible that the impaired brain metabolism due to elevated blood ammonia is liable to cause disturbance of consciousness or to precipitate coma. Varieties of treatments lowering the elevated blood level of ammonia have been reported to be effective in relieving the symptoms and improving the pathological conditions of ammonia intoxication. Greenstein et al. (8, 9) and other workers (10-12) dealt with L-arginine ; White and Berenbom (13) and other workers (14-17) studied L-glutamic acid; and Laborit et al. (18-20), Fodor et al. (21), and Tamaki et al. (22) examined Laspartic acid. The findings of these authors support the usefulness of three compounds in reducing the blood level of ammonia, and all three compounds are enjoying clinical use. One may point out the important role of L-ornithine in metabolic process in the body, if he appreciates the critical function of the urea cycle and the TCA cycle. Salvatore and Bocchini (23) obtained an excellent result with concomitant use of Laspartic acid and L-ornithine in protecting the toxic effect of ammonium acetate as compared with the use of L-aspartic acid alone. Salvatore et al. (24, 25) also reported the superiority of the combined medication in chronic intoxication of carbon tetrachloride. The present paper is concerned with general pharmacology of L-ornithine L-aspartate and effects of the compound upon ammonia and carbon tetrachloride intoxications.