Effect of Orally Administered L–Carnitine on Blood Ammonia and L–Carnitine Concentrations in Portacaval–Shunted Rats

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Abstract
L–Carnitine (16 mmoles per kg, injected intraperitoneally) is reported to protect mice against subsequent injection of ammonium acetate given at the unprotected LD100. The present studies in rats show a variable protective effect of l–carnitine (16 mmoles per kg) administered 1 hr prior to an LD100 dose of ammonium acetate. Survival ranged from 100% to 35%. In two experiments, protection was highly significant; in a third experiment, l–carnitine did not protect against death but did significantly prolong time to death. Although the cause of this variability is not known, the data establish the protective effect in rats of l–carnitine given 1 hr before ammonium acetate. d–Carnitine and deoxycarnitine, chemically related analogs unable to substitute for l–carnitine metabolically, are without protective effect. The protective effect of l–carnitine is short–lived and is, for example, completely lost if ammonium acetate is given 24 hr after l–carnitine administration. In contrast, the free carnitine content of brain rises slowly but continuously for at least 24 hr following a single dose of l–carnitine. The observation that protection from ammonia toxicity is not correlated with brain carnitine levels strongly suggests a major peripheral component to the protective effect. Chronically hyperammonemic (portacaval–shunted) rats were found to have significantly depressed total and free carnitine levels in blood compared to normal and sham–operated controls. The hypocarnitinemia, but not the hyperammonemia, was completely reversed in portacaval–shunted rats given drinking water containing 10 mM l–carnitine. No abnormal behavioral effects were noted in portacaval–shunted or control rats given l–carnitine for 16 weeks, and carnitine did not affect growth or fluid intake. Since carnitine levels are decreased in the serum of some patients with a variety of hyperammonemic syndromes, the present findings may be of clinical relevance to the long–term treatment of these diseases.