Context:d-Glucaro-1,4-lactone (1,4-GL) exists in many vegetables and fruits. Metabonomics has not been used to investigate the role of 1,4-GL in preventing liver cancer.Objective: The pharmacological effects and metabolite alterations of 1,4-GL on the prevention of diethylnitrosamine (DEN)-induced liver cancer were investigated.Materials and methods: Ten healthy Sprague–Dawley rats served as control and 46 were used to establish rat liver cancer model. 1HNMR-based metabonomics was used to compare the effects of oral 1,4-GL (50 mg/kg) in liver cancer rats (n = 26) after 10 consecutive weeks of intervention. The amino acids in rat serum were quantified by HPLC-UV, and the changes in Fischer’s ratio were calculated.Results: The 20-week survival rate of DEN-induced liver cancer rats administered with oral 1,4-GL was increased from 45.0 to 70.0% with reduced carcinogenesis of the liver and significantly lowered serum α-fetoprotein level (14.28 ± 2.89 ng/mL vs. 18.56 ± 4.65 ng/mL, p = 0.012). The serum levels of leucine, valine, 3-hydroxybutyrate, lactate, acetate and glutamine in the DEN + 1,4-GL group returned to normal levels compared with those of the DEN group on week 20. Fischer’s ratio in the rat serum of DEN group was 1.62 ± 0.21, which was significantly lower than that in healthy rats (2.3 ± 0.12). However, Fischer’s ratio increased to 1.89 ± 0.22 in the DEN + 1,4-GL group.Discussion and conclusions: 1,4-GL exerted positive effects on liver carcinogenesis in rats by pathological examination and metabonomic analysis. Its mechanism may be related to the restoration of amino acid and energy metabolism.
Artificial liver support systems (ALSSs) have been recommended as important approaches for treating liver fuilure (LF) patients. However, very few studies have focused on the screening of potential serum therapeutic markers of LF patients treated by ALSSs. Here, serum samples were obtained from 57 LF patients before and after ALSSs treatment and analyzed by metabonomics. The results showed that ratios of creatine:creatinine, taurine:creatinine, and lactate:creatinine were significantly altered and restored to normal levels after ALSSs treatment. The ratio of lactate:creatinine showed the highest area under a receiver-operating characteristic curve (AUROC) value (0.650), which was higher than that of the prothrombin time activity (PTA, 0.562). A retrospective analysis showed that serum lactate:creatinine ratios among the LF patient groups were 0.038 ± 0.002 (survival group, n=48), 0.048 ± 0.005 (three-month death group, n=24), and 0.052 ± 0.005 (one-month death group, n=33), which was significantly negatively correlated with survival (r= - 0.26). Another retrospective cohort analysis (n=81) of LF patients showed that the lactate-creatinine ratio in the death group remained unchanged, but fell markedly in the survival group (0.052 ± 0.005 vs. 0.025 ± 0.002) after ALSSs treatment. In comparison, the serum PTA levels were no statistical differences of in both the death group and survival group after ALSSs treatment. The AUROC of serum lactate-creatinine ratio and PTA after ALSSs treatment for diagnosis of survival group from death group was 0.682 and 0.591 respectively. These results indicate that the serum lactate-creatinine ratio may be more reliable than measures of PTA to evaluate the therapeutic effect of ALSSs treatment in LF patients.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.