What do we know about Aristolochia toxicity?
Aristolochia are aromatic decorative plants that grow all around the world. Most species can be found in the Mediterranean and in Asia. These plants contain biologically active compounds named after the genus – aristolochic acids I and II. Both cause mutations leading to carcinogenic growth and are classified as group 1 carcinogens. However, their interactions with each other within live organisms have been underexplored. An international team of scientists, with the main contribution provided by the research group of Professors Marie Stiborová and Petr Hodek from the Faculty of Science, Charles University, decided to change this.
Aristolochic acids cause two kinds of nephropathy (damage of the kidneys) and related upper urothelial cancer. To date, scientists have primarily explored the effect on those diseases of the enzymatic activation of aristolochic acid I. However, in nature, both acids are present in each plant. Therefore, it is important to examine their mutual interactions. For instance, Professor Stiborová’s team previously demonstrated that the metabolism of both aristolochic acids is affected by their mutual interactions. In this study, they examined this effect with respect to the formation of DNA adducts (the genetic damage these compounds cause).
zdroj: https://cs.wikipedia.org/wiki/Podra%C5%BEec
The mutual interactions of aristolochic acids were studied using a rat model. One group of rats were exposed to aristolochic acid I (AAI) alone, the second to aristolochic acid II (AAII) alone, and the third to a mixture of both acids. Initial results indicated that the metabolism of AAI was reinforced in the presence of both compounds while the metabolism of AAII was weakened. This can lead to higher production of the toxic AAI adducts, which are responsible for the carcinogenetic effect of the said compounds. Based on this, the scientists then studied the formation of DNA adducts in individual groups of rats. Animals exposed to a mixture of both acids had up to 2.5 times more DNA adducts than rats exposed to only one acid. The most striking difference was the number of AAI adducts in adenine (one of four nucleic bases in DNA) which exhibited levels up to 4.5 times higher after administration of an AAI/AAII mixture than AAI alone. In all individuals, the occurrence was highest in kidneys, which confirmed that kidneys are the main target of Aristolochic toxicity. Also affected (albeit to a lesser extent) is the liver as the main biotransformation (metabolic) organ.
This study has revealed that while AAI alone is genotoxic, its toxicity is enhanced by the presence of AAII, which is also toxic on its own. This phenomenon is likely to be attributable to the fact that AAII blocks AAI detoxification, which means AAI remains in the organism for longer and can cause more damage.
The research draws attention to the need to take both acids into consideration when studying the aetiological mechanisms underpinning aristolochic acid nephropathy, such as Balkan endemic nephropathy linked to upper urothelial cancer. Potentially, millions of people are at risk of developing this type of disease as Aristolochia continue to be used in traditional Asian medicine and are randomly found in flour-based foods.
Magda Křelinová
Published:
Dec 07, 2021 08:15 PM
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