THESIS
2017
xxiv, 154 pages : illustrations ; 30 cm
Abstract
Aristolochic acids (AAs), are natural constituents identified in Aristolochia
plants utilized in Chinese traditional medicine and they are also parts of a lot of herbal
remedies adopted all over the world. In human beings, AA exposure can lead to kidney
toxicity or rare upper urinary tract cancer (UUC). Evidence has emerged, showing
that AAs are associated with the development of Balkan endemic nephropathy (BEN)
which is a progressive renal illness inflicting a large number of peasants dwelling in
the Balkan Peninsula. Regrettably, how AAs get into the human food cycle and lead
to kidney dysfunction is still elusive.
The hypothesis guiding the study was the possibility that free AAs derived from
decayed Aristolochia clematitis in the fields would be uptaken from the soil by pla...[
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Aristolochic acids (AAs), are natural constituents identified in Aristolochia
plants utilized in Chinese traditional medicine and they are also parts of a lot of herbal
remedies adopted all over the world. In human beings, AA exposure can lead to kidney
toxicity or rare upper urinary tract cancer (UUC). Evidence has emerged, showing
that AAs are associated with the development of Balkan endemic nephropathy (BEN)
which is a progressive renal illness inflicting a large number of peasants dwelling in
the Balkan Peninsula. Regrettably, how AAs get into the human food cycle and lead
to kidney dysfunction is still elusive.
The hypothesis guiding the study was the possibility that free AAs derived from
decayed Aristolochia clematitis in the fields would be uptaken from the soil by plants
growing nearby, thereby transferring this potent human carcinogen and nephrotoxin
into the edible parts. Applying the formerly created method of analysis which is sensitive
and selective (Chan et al., 2007), the study measures AAs in lettuce, tomato, as
well as spring onion planted in AA polluted land and culture medium. Results suggest
that AAs are absorbed from the land and gathered biologically in lettuce in a way that
depends on time as well as dose.
To better confirm the assumption that environmental contamination by AAs and
root uptake of AAs in the contaminated soil could be one of the pathways by which
AAs enter the human food chain, we also analyzed farmland soil and food crops collected
from both non-endemic and endemic areas in Serbia, we discovered that environmental
and food pollution by AAs from the decomposition of Aristolochia clematitis
is one of the main causes to BEN. Data also showed AAs are highly stable in the
soil environment and during the heat-treatment process, indicating AAs are persistent
environmental and food contaminants and is able predisposed to be up taken by food
crops and end upturned out in bread. As far as we know, this is the first research that
agricultural soil and grains in the endemic area are being extensively contaminated
with AAs. We believe the results from this report have disclosed a hidden, but important
public health problem: the occurrence of a new type of potent nephrotoxic and
carcinogenic toxicant in both the environment and food.
In other hand, although decades of research have gone, the potential impact on
proteins is elusive, and the specific mechanism of nephrotoxicity remains unclear because
of the observed toxicity of AA is poorly understood. In order to better understand
the toxicological AA characteristics, the covalent and noncovalent interaction
between AA and proteins was investigated in this study. Through mass spectrometry
(MS) and fluorescence spectra, we characterized the protein binding characters of AA
and BSA and lysozyme. In addition, a sensitive high-performance liquid chromatography
together with fluorescence detection (HPLC-FLD) method was used to assess
acid-labile albumin−AA ad-ducts in vitro managed a dietary-associated amount of
aristolactams. We can also detected released aristolactams from AA-protein adducts in
AA dosed SD-rats tissues. This is the first direct report to demonstrate both covalent
and noncovalent binding of protein-AA complexes to the best of our knowledge.
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