背景:据报道,灰狗患有高同型半胱氨酸血症(HHC),但潜在的机制和临床意义尚不清楚.
目的:我们的主要目的是评估灰狗血清同型半胱氨酸(HCy)和相关分析物的浓度,并确定可能的HHC代谢途径。次要目的是确定HHC是否与氧化应激的证据相关。
方法:健康的宠物灰狗(n=31)和非猎犬对照狗(n=15)。
方法:血清HCy,钴胺素,叶酸,和蛋氨酸,和血浆半胱氨酸,谷胱甘肽,和总的8-异前列腺素浓度。
结果:灰狗的同型半胱氨酸浓度更高(中位数,25.0μmol/L)与对照组(13.9μmol/L;P<0.0001)相比。灵狮中的钴胺浓度较低(中位数,416ng/L)与对照组(644ng/L;P=.004)相比,与HCy呈负相关(r=-0.40,P=.004)。叶酸的血清浓度,当HCy转化为蛋氨酸时再生,与HCy呈负相关(r=-0.47,P=0.002)。灰狗的血清蛋氨酸浓度降低了4倍以上(中位数,3.2μmol/L)与对照组(中位数,15.0μmol/L),但差异不显著(P=3)。血浆半胱氨酸,谷胱甘肽,8-异前列腺素浓度在组间没有显著差异。
结论:我们的研究结果表明,灰狗体内HCy转化为甲硫氨酸的主要缺陷,与相关的叶酸生成受损。蛋氨酸合酶的无效循环可能导致继发性钴胺素消耗。值得注意的是,在灰狗中可以观察到低血清叶酸和钴胺素浓度,而没有肠道疾病的迹象。
BACKGROUND: Greyhounds have been reported to have hyperhomocysteinemia (HHC), but the underlying mechanisms and clinical implications are unclear.
OBJECTIVE: Our primary aim was to assess serum concentrations of homocysteine (HCy) and related analytes in Greyhounds and to identify a likely metabolic pathway for HHC. A secondary aim was to determine whether HHC is associated with evidence of oxidative stress.
METHODS: Healthy pet Greyhounds (n = 31) and non-sighthound control dogs (n = 15).
METHODS: Analysis of serum HCy, cobalamin, folate, and methionine, and plasma cysteine, glutathione, and total 8-isoprostane concentrations.
RESULTS: Homocysteine concentrations were higher in Greyhounds (median, 25.0 μmol/L) compared to controls (13.9 μmol/L; P < .0001). Cobalamin concentrations were lower in Greyhounds (median, 416 ng/L) compared to controls (644 ng/L; P = .004) and were inversely correlated with HCy (r = -0.40, P = .004). Serum concentrations of folate, which is regenerated when HCy is converted to methionine, also were inversely correlated with HCy (r = -0.47, P = .002). Serum methionine concentrations were more than 4-fold lower in Greyhounds (median, 3.2 μmol/L) compared to controls (median, 15.0 μmol/L), but this difference was not significant (P = .3). Plasma cysteine, glutathione, and 8-isoprostane concentrations did not differ significantly between groups.
CONCLUSIONS: Our findings suggest a primary defect in conversion of HCy to methionine in Greyhounds, with related impaired folate generation. Ineffective cycling by methionine synthase could lead to secondary cobalamin depletion. Notably, low serum folate and cobalamin concentrations can be observed in Greyhounds without signs of intestinal disease.