L-carnitine protection in ammonia intoxication. Effect of aminocarnitine on carnitine-dependent metabolism and acute ammonia toxicity.
L-carnitine protection in ammonia intoxication. Effect of aminocarnitine on carnitine-dependent metabolism and acute ammonia toxicity.
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左旋肉碱对氨中毒有保护作用。
DOI：
10.1016/0006-2952(91)90136-s
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发表时间：
1991
影响因子：
5.8
通讯作者：
Griffith,OW
中科院分区：
文献类型：
--
作者：
Ohtsuka,Y;Griffith,OW
O' conconret . （FEBS let166: 331-334, 1984）报道腹腔注射左旋肉碱（16 mmol/kg）可以完全保护小鼠免受醋酸铵的伤害，醋酸铵的剂量使未处理的对照组100%死亡。其他研究人员要么未能观察到左旋肉碱的保护作用，要么将生存的增加归因于季铵化合物的非特异性“渗透保护作用”。在目前的研究中，我们证实了左旋肉碱对急性氨中毒的保护作用，并表明-左旋肉碱和脱氧左旋肉碱是左旋肉碱的结构类似物，没有保护作用。虽然左旋肉碱和脱氧左旋肉碱不支持左旋肉碱依赖代谢，但它们被运输到组织中，它们的溶液与左旋肉碱的溶液具有渗透性相同；缺乏左旋肉碱和脱氧左旋肉碱的保护表明，代谢而非非特异性渗透作用是左旋肉碱介导的保护的原因。进一步支持了左旋肉碱依赖性代谢的重要性，我们发现，当用左旋肉碱、乙酰氨基左旋肉碱或棕榈酰氨基左旋肉碱进行预处理时，小鼠对乙酸铵的敏感性增加，这些都是左旋肉碱酰基转移酶的有效抑制剂。有趣的是，腹膜内注射高渗氯化钠或蔗糖溶液确实对随后施用的醋酸铵具有显著的保护作用。这种现象可能是由于干扰了从腹膜腔摄取乙酸铵或通过增加血浆渗透压减少脑水肿，显然在肉毒碱介导的保护中不起主要作用，因为，如前所述，高渗肉毒碱和脱氧肉毒碱溶液没有保护作用。
Intraperitoneal administration ofl-carnitine (16 mmol/kg) was reported by O'Connoret al. (FEBS Lett166: 331–334, 1984) to fully protect mice from ammonium acetate given at a dose that kills 100% of untreated controls. Other investigators either have failed to observe protection byl-carnitine or have attributed the increased survival to a nonspecific “osmoprotective effect” of quaternary ammonium compounds. In the present studies we have confirmed the protective effect ofl-carnitine in acute ammonia intoxication and have shown thatd-carnitine and deoxycarnitine, close structural analogs ofl-carnitine, are without protective effect. Althoughd-carnitine and deoxycarnitine do not supportl-carnitine-dependent metabolisms, they are transported into tissues and their solutions are osmotically identical to those ofl-carnitine; lack of protection byd-carnitine and deoxycarnitine suggests that metabolic rather than nonspecific osmotic effects account forl-carnitine-mediated protection. Further supporting the importance ofl-carnitine-dependent metabolisms, we found that mice exhibited increased sensitivity to ammonium acetate when pretreated withdl-aminocarnitine, acetyl-dl-aminocarnitine or palmitoyl-dl-aminocarnitine, potent inhibitors of the carnitine acyltransferases. Interestingly, intra-peritoneal injection of hyperosmotic solutions of sodium chloride or sucrose did afford significant protection against subsequently administered ammonium acetate. This phenomenon, which may be due to interference with ammonium acetate uptake from the peritoneal cavity or to reduction of cerebral edema by increased plasma osmolarity, apparently does not play a major role inl-carnitine-mediated protection since, as noted, hyperosmoticd-carnitine and deoxycarnitine solutions were not protective.