Aristolochia species are toxic plants used as herbal medicines worldwide. They are known to cause aristolochic acid nephropathy (AAN), a disease associated with kidney failure and kidney cancer. Aristolochic acid (AA) I and AA II are considered to be responsible for AAN. However, a wide range of aristolochic acid analogues exists and their implication in AAN may have been overlooked. The aims of this project are to assess the health risks associated with different Aristolochia species and to elucidate the principles behind their nephrotoxic effects. 44 medicinally used Aristolochia species were analyzed using LC-MS and 1H- NMR. The cytotoxicity and genotoxicity of 28 Aristolochia extracts was measured in human kidney (HK-2) cells. Several AAAs were isolated from natural sources. Their molecular mechanisms were analysed in hepatoma G2 (Hep G2) cells. Furthermore, we studied ethnobotanical uses of Aristolochia indica L. in Bangladesh. AA I and AA II are the most common AAAs. However, aristolactam (AL) I, AA IV and AL BI are widespread as well. Several of the extracts caused cytotoxic effects and micronuclei induction in HK-2 cells. No correlation was found between the amounts of AA I or AA II and the extractsʼ toxicity. While both AA I and AA II formed DNA adducts in Hep G2 cells, only AA I was cytotoxic and caused oxidative stress. AL I and AA IIIa caused oxidative stress to a lesser extent. Other components exhibited no toxic effects. Furthermore we demonstrated that Aristolocha indica is widely available in Bangladesh and more awareness needs to be raised about the health risks associated its use. By linking a metabolomic analysis with in vitro studies, we were able to show that the assumption that the toxicity of Aristolochia species is caused by AA I and AA II alone is incorrect.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:631875 |
| Date | January 2014 |
| Creators | Michl, J. |
| Publisher | University College London (University of London) |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://discovery.ucl.ac.uk/1431716/ |
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