A latest study has shown that Aristolochic Acids (AA) – that are commonly used as a natural product found in some natural remedies, could be associated with liver cancers. Researchers from Singapore and Taiwan showed in their study that AA could be causing mutations in the genes that predispose an individual to liver cancers. Their study, Aristolochic acids and their derivatives are widely implicated in liver cancers in Taiwan and throughout Asia, was published yesterday (18th October 2017) in the latest issue of Science Translational Medicine.
The team of researchers led by Professor Steven Rozen from Duke-NUS Medical School first looked at the DNA sequences of 98 liver cancers detected in Taiwan. They then analyzed the mutations of these individuals using mutational signature analysis. Their results revealed that as many as 78 percent of these mutations were the result of AA. Mutational signatures are good at predicting patterns of DNA changes that are caused due to mutagens or chemicals and agents that are capable of causing DNA mutations. Professor Hsieh Sen-Yung from Chang Gung Memorial Hospital in Taiwan, who was part of the study explained that exposure to AA is well documented in Taiwan from the herbal remedies. What is new in this study is the number of liver cancers that are associated with this compound.
After analyzing the DNA of the liver cancers the team looked into the mutational data from 1,400 liver cancer patients worldwide. They included liver cancer cases from China, Korea, Japan, Vietnam, other regions in Southeast Asia, France, Italy, Spain, and parts of North America. Exposure to AA is seen in several other regions mainly East and Southeast Asia, mostly from traditional herbal medicines. Professor Rozen noted that this exposure data was also a revelation. The connection between the compound and liver cancer was clearer he explained. AA, he added, is a known mutagen that has been linked to kidney and urinary tract cancers in Taiwan. This compound has been liked to severe kidney damage called Balkan nephropathy seen in Bosnia, Bulgaria, Croatia, Romania and Serbia. This was the first study that connected AA with liver cancer he explained.
Aristolochic Acid is a naturally occurring compound found in Aristolochia and Asarum plants. There are nearly 500 species of Aristolochia, and of these nearly a 100 are used in herbal remedies. Rozen said that these plants have beautiful trumpet shaped flowers that give then the name “Dutchman’s pipe”. The flowers, roots and stems of the plants have been used in form of extracts in herbal medicines.
These plants are routinely used as part of traditional herbal remedies especially for medicines used for slimming and weight loss. Europe has banned AA 2001 and Singapore followed suit in 2004. Taiwan too has banned herbals with AA since 2003. China and United States drug authorities have restricted their usage with warnings to users. Researchers say that these liver cancer cases are a result of the use of this compound in medications much before the bans were in place. So it may still take a few years before the rates of liver cancers associated with AA stop. Further, there is no dearth of online availability of herbal remedies that contain AA. Many of these are inadequately labeled and so consumers have no clue that they are consuming AA containing medications.
Professor Teh Bin Tean from the National Cancer Centre Singapore and Professor Alex Chang from Johns Hopkins Medicine Singapore were also part of this study. Professor Chang said the only way to stop this was to increase public awareness.
Understanding metabolic alterations and immune dysfunction in acute-on-chronic liver failure