Matsuoka M, Igisu H
Department of Environmental Toxicology, University of Occupational and Environmental health, Kitakyushu, Japan.
Biochem Pharmacol. 1993 Jul 6;46(1):159-64. doi: 10.1016/0006-2952(93)90360-9.
Although L-carnitine has been reported to have protective effects against ammonia toxicity, conflicting results have also been presented and the mechanisms underlying the protection, if any, are not clear. In the present study, we examined the effects of L-carnitine, D-carnitine and acetyl-L-carnitine on the neurotoxicity of ammonia. Administration of ammonium acetate (15 mmol/kg) to mice caused seizures, elevation of blood ammonia and urea concentrations, and marked alterations of brain energy metabolites. Pretreatment with either L-carnitine, D-carnitine or acetyl-L-carnitine reduced the frequency of the seizures, prolonged the time until the first fit, lowered the levels of ammonia in the blood and brain, and suppressed the alterations of brain energy metabolites caused by hyperammonemia. there was no significant difference between L- and D-carnitine in the potency to inhibit the seizures. In addition, there was no difference between the two chemicals in the potency to decrease the ammonia contents in the blood and brain, or to suppress the alterations of energy metabolites in the brain. When compared with L-carnitine, however, acetyl-L-carnitine better preserved ATP in the brain, while it lowered ammonia in the blood and brain less markedly. These results show that L-carnitine and its analogues do have the potential to suppress the neurotoxicity of ammonia. Moreover, the results suggest that the protective effects of carnitine against the toxicity of ammonia are systemic, that the action of acetyl-L-carnitine may differ from that of L- or D-carnitine, and that the "classical" function of carnitine is not the sole mechanism underlying the suppression of the neurotoxicity of ammonia.
尽管已有报道称左旋肉碱对氨毒性具有保护作用，但也有相互矛盾的结果出现，而且其保护机制（如果存在的话）尚不清楚。在本研究中，我们检测了左旋肉碱、右旋肉碱和乙酰左旋肉碱对氨神经毒性的影响。给小鼠腹腔注射醋酸铵（15 mmol/kg）会引发惊厥、血氨和尿素浓度升高，以及脑能量代谢产物的显著变化。用左旋肉碱、右旋肉碱或乙酰左旋肉碱预处理可降低惊厥频率、延长首次惊厥发作时间、降低血液和脑组织中的氨水平，并抑制高氨血症引起的脑能量代谢产物变化。左旋肉碱和右旋肉碱在抑制惊厥的效力上没有显著差异。此外，这两种化合物在降低血液和脑组织中氨含量或抑制脑能量代谢产物变化的效力上也没有差异。然而，与左旋肉碱相比，乙酰左旋肉碱能更好地维持脑中的ATP水平，而其降低血液和脑组织中氨水平的作用则不太明显。这些结果表明，左旋肉碱及其类似物确实具有抑制氨神经毒性的潜力。此外，结果还表明肉碱对氨毒性的保护作用是全身性的，乙酰左旋肉碱的作用可能与左旋或右旋肉碱不同，而且肉碱的“经典”功能并非抑制氨神经毒性的唯一机制。
