Todorova Valentina, Vanderpool Doug, Blossom Sarah, Nwokedi Emmanuel, Hennings Leah, Mrak Robert, Klimberg V Suzanne
Department of Surgery, University of Arkansas for Medical Sciences, Little Rock, USA.
Nutrition. 2009 Jul-Aug;25(7-8):812-7. doi: 10.1016/j.nut.2009.01.004. Epub 2009 Feb 28.
This study evaluated the effects of supplemental oral glutamine (GLN) on acute cardiotoxicity of cyclophosphamide (CPA) in experimental rats. The dose-related cardiotoxicity of CPA is associated with a rapid decrease in cardiac glutathione (GSH) and oxidative cardiac injury. GLN is a rate-limiting precursor for GSH synthesis during periods of oxidative and other types of stress when it becomes a conditionally essential amino acid.
Forty-four male Fischer 344 rats were randomized into two groups to receive 1 g.kg(-1).d(-1) of GLN or glycine by gavage. After 2 d of prefeeding, each of these groups was further randomized into three subgroups to receive intraperitoneally a lethal dose of CPA (450 mg/kg), a sublethal dose of CPA (200 mg/kg), or saline (controls). Twenty-four hours later all six groups of rats were sacrificed and blood GLN was measured. Cardiac tissue was examined for histopathologic alterations: GSH and oxidized GSH concentrations.
The results showed that dietary GLN decreased cardiac necrosis and maintained normal cardiac GSH levels. Elevated cardiac GSH levels in the GLN group correlated with increased arterial GLN levels. GLN protected against the acute cardiotoxic effects of CPA and significantly improved the short-term survival after lethal and sublethal doses of CPA.
These data suggest that GLN may protect against CPA-related cardiac injury through maintenance of cardiac GSH metabolism.
本研究评估了补充口服谷氨酰胺（GLN）对实验大鼠环磷酰胺（CPA）急性心脏毒性的影响。CPA的剂量相关心脏毒性与心脏谷胱甘肽（GSH）的快速降低及心脏氧化损伤有关。在氧化应激和其他类型应激期间，当GLN成为条件必需氨基酸时，它是GSH合成的限速前体。
44只雄性Fischer 344大鼠被随机分为两组，通过灌胃分别给予1 g·kg-1·d-1的GLN或甘氨酸。预喂养2天后，每组再进一步随机分为三个亚组，分别腹腔注射致死剂量的CPA（450 mg/kg）、亚致死剂量的CPA（200 mg/kg）或生理盐水（对照组）。24小时后，处死所有六组大鼠并测量血液中的GLN。检查心脏组织的组织病理学改变：GSH和氧化型GSH浓度。
结果表明，饮食中的GLN减少了心脏坏死并维持了正常的心脏GSH水平。GLN组心脏GSH水平升高与动脉GLN水平升高相关。GLN可预防CPA的急性心脏毒性作用，并显著提高致死和亚致死剂量CPA后的短期存活率。
这些数据表明，GLN可能通过维持心脏GSH代谢来预防与CPA相关的心脏损伤。
