# Impact of Dietary Practices on DNA Adduct Formation by Aristolochic Acid I in Mice: Drinking Alkaline Water as a Risk Mitigation Strategy

## TL;DR

This study shows that unbalanced diets increase DNA damage from aristolochic acids, a cause of kidney disease, while alkaline water reduces this risk.

## Contribution

The study identifies dietary factors influencing DNA adduct formation from aristolochic acids and proposes alkaline water as a risk mitigation strategy.

## Key findings

- Unbalanced diets significantly increase DNA adduct formation from aristolochic acids.
- Alkaline water reduces DNA adduct levels by 30% compared to tap water.
- Vitamin C and cysteine supplements increase DNA adducts by enhancing AA metabolism.

## Abstract

Balkan endemic nephropathy
(BEN) is a chronic kidney disease associated
with the consumption of aristolochic acids (AAs) through contaminated
food sources. AAs are known to form DNA adducts that are implicated
in tumorigenesis and kidney fibrosis. Given the sensitivity of DNA
adduct formation to dietary factors, this study aimed to investigate
the impact of various dietary practices on AA-DNA adduct formation,
thereby assessing the risk of developing BEN. We quantified AA-DNA
adducts in DNA extracted from the kidneys and livers of mice subjected
to high-fat, high-protein, high-sucrose, and high-salt diets, utilizing
a highly sensitive liquid chromatography–tandem mass spectrometry
method combined with stable isotope dilution. Our results demonstrated
that unbalanced diets significantly elevated the formation of DNA
adducts from AAs. Notably, mice fed high-fat diets exhibited increases
in adduct levels of 71 and 114% for diets containing 17 and 25% fat,
respectively. Mice on a 20% sucrose diet showed an 80% increase in
adduct levels compared to those on a standard diet. Further investigations
using gut sacs from the small intestines of these mice revealed that
the increased level of DNA adduct formation was primarily attributed
to enhanced intestinal absorption. Additionally, we observed that
drinking alkaline water reduced adduct levels by 30% compared to tap
water, likely by decreasing AA absorption. In contrast, commonly used
dietary supplements, such as vitamin C and cysteine, significantly
increased AA-DNA adduct levels by enhancing the activity of enzymes
involved in the metabolic activation of AAs. These findings highlight
the critical role of a balanced diet in mitigating the risk of BEN
and suggest that alkaline water consumption may serve as a protective
strategy for individuals living in AA-contaminated regions.