Imbalance between vasoactive substances in experimental Aristolochic Acid Nephropathy

Abstract

The term “aristolochic acid nephropathy” (AAN) is used to include any form of toxic interstitial nephropathy that is caused either by ingestion of plants containing aristolochic acids (AA) as part of traditional phytotherapies (formerly known as “Chinese herbs nephropathy”), or by the environmental contaminants in food (Balkan endemic nephropathy). It is also frequently associated with urothelial malignancies. Although products containing AA have been banned in most of countries, AAN cases remain regularly reported all over the world. Experimental models have been developed to improve the comprehension of the underlying pathological mechanisms of AA toxicity and to identify potential targets for therapy. In this work, the first objective was to validate a mouse model of AAN. The model that we developed presented characteristic features of AAN. The second objective was to investigate whether endothelial dysfunction occurs following AA intoxication and at which extend it contributes to AA toxicity. In this regard, we highlighted that an imbalance between vasoactive substances occurred following AA intoxication. We demonstrated that the vasodilator, nitric oxide, is reduced whereas the potent constrictor, endothelin, is strongly induced. These concomitant observations lead us to the conclusion that this imbalance tips in favor of a vasoconstrictive state within the kidney that may contribute to renal hypoxia thereby leading to the final pathway of renal fibrosis in AAN.

Date of Award	2019
Original language	English
Awarding Institution	University of Namur
Sponsors	University of Namur
Supervisor	Nathalie Caron (Supervisor), Anne-Emilie Decleves (Co-Supervisor), Carine Michiels (President), Charles Nicaise (Jury), Joëlle Nortier (Jury), Jean-Marie Colet (Jury) & Christos Chatziantoniou (Jury)