Metabonomics of d-glucaro-1,4-lactone in preventing diethylnitrosamine-induced liver cancer in rats

Abstract

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.

Elevated Serum Uric Acid is Associated With Poor Survival in Advanced HCC Patients and Febuxostat Improves Prognosis in HCC Rats

“…After febuxostat intervention, the serum AFP level showed a decreasing trend (7.937 ± 0.973). Furthermore, the serum levels of leucine, isoleucine, valine, phenylalanine, and tyrosine were determined by an established HPLC-UV method, and Fisher’s ratio was calculated ( Yang et al, 2018 ). Our results showed that Fisher’s ratio was significantly decreased in the DEN group compared with the healthy control group and significantly increased in the DEN + Febu group compared with the DEN group ( Figure 4B ).…”

Serum metabolomics in chickens infected with Cryptosporidium baileyi

“…breast cancer, liver cancer) and microbial diseases (e.g. hepatitis B, tuberculosis) [ 15 , 17 , 19 , 21 , 22 , 34 , 44 , 45 ]. In 2012, Ng et al developed an untargeted metabolomics method using GC–MS to compare differences in metabolites present in fecal extractions from Cryptosporidium -positive and Cryptosporidium -negative patients [ 46 ], ultimately identifying 30 possible compounds that contributed most to the differences between two groups.…”

Hepatic Encephalopathy: Current and Emerging Treatment Modalities

“…45 Decreased serum BCAA/AAA ratio in the serum (especially BCAA/AAA <3) promotes HE development as more AAA enters the brain, leading to production of false neurotransmitters that replace major brain neurotransmitters. [46][47][48][49][50] Another reason for HE development with decreased BCAA levels is that skeletal muscles use BCAAs as energy sources to resynthesize glutamine that facilitates ammonia removal. 48 Therefore, oral BCAA supplementation can favor glutamine production in skeletal muscles, leading to ammonia removal and improvement in HE.…”