Mitigation of Fumonisin Biomarkers by Green Tea Polyphenols in a High-Risk Population of Hepatocellular Carcinoma

It is a ubiquitous contaminant of cereal grains, with at least 15 variants isolated, including A, B, C, and P variants. FB1 causes several fatal animal diseases, including leukoencephalomalacia in horses, pulmonary oedema in swine, neural tube defects in mice, nephrotoxicity in rodents, and hepatotoxicity in horses, swine, and rats. Additionally, FB1 is a carcinogen and strong promoter of tumorigenesis in animal and human models. Human populations in certain areas of the world are exposed to higher levels of FB1 in their diets, mainly through the ingestion of contaminated corn and corn-based foods. Aetiologically, FB1 exposure has been linked to a broad spectrum of human diseases, including hepatocellular carcinoma and oesophageal cancer in South Africa, China, and the Islamic Republic of Iran. The International Agency for Research on Cancer (IARC) has classified FB1 as a group 2B carcinogen. The possible mechanism of action of FB1 involves the inhibition of ceramide synthases and disruption of lipid metabolism. FB1 disrupts sphingolipid metabolism by inhibiting ceramide synthases, due to its structural similarity to long-chain sphingoid base backbones. The inhibition of ceramide synthases causes an increase in intracellular free sphinganine (Sa) and sphingosine (So), which precedes the depletion of complex bioactive lipids. FB1-induced biochemical alterations, particularly the elevated Sa levels, Sa to So ratio, or Sa 1-phosphate to So 1-phosphate (SaP/SoP) in tissues, urine, and urine, have been proposed as biomarkers in various animal species, including foals, pigs, mink, rodents, vervet monkeys, and ducks. Toxicokinetic studies have shown that orally dosed FB1 is eliminated rapidly from the body, with a lack of a major metabolite. This rapid elimination and low bioavailability indicate that FB1 in biological fluids can be measured directly as a biomarker of FB1 exposure. Free FB1 has been applied as a biomarker in many studies to track FB1 exposure and intervention strategies that reduce exposure to FB1. A study was conducted to assess the mitigation of FB1 biomarkers by green tea polyphenols (GTP) in a high-risk population of hepatocellular carcinoma. A total of 124 subjects were recruited and randomized into three treatment arms: placebo, low-dose GTP, and high-dose GTP. Blood and urine samples were collected before treatment to determine the baseline levels of FB1 biomarkers, including urinary free FB1, urinary and serum Sa, So, and Sa/So ratio. The baseline levels of FB1 biomarkers were obtained via analyzing the screening samples. The detectable rate of urinary free FB1 was 91.2%, with an average level of 797.66 pg/mg creatinine and a median level of 560.73 pg/mg creatinine. Sphingolipids were detectable in 100% of the screening samples, with average levels, median, lower quartile, and upper quartile of Sa, So, and Sa/So ratio in serum and urine samples. After one month of GTP intervention, the median levels of urinary free FB1 were 575.25, 477.79, and 364.94 pg/mg creatinine in the placebo, low-dose, and high-dose GTP groups, respectively. The reduction rate was 18.95% in the low-dose group and 33.62% in the high-dose group compared to the placebo group. The urinary free FB1 level in the high-dose group was significantly lower than that in the placebo group (p = 0.045). After three months of intervention, urinary free FB1 levels continued to decrease in both the low-dose and high-dose GTP groups compared to the placebo group. The reduction rate was 40.18% in the low-dose group and 52.6% in the high-dose group. GTP treatment significantly reduced urinary excretion of sphinganine (Sa), sphingosine (So), and Sa/So ratio, but had no effect on serum Sa, So, and Sa/So ratio.