Chronic toxicity of crude ricinine in rats assessed by 1H NMR metabolomics analysis

Abstract

Ricinine is a toxic alkaloid found in the leaves and seeds of Ricinus communis L. It can cause vomiting and various other toxic reactions, including liver and kidney damage, convulsions, and hypotension, and can even lead to death. In this study, rats were orally administrated with an extract of castor bean shell (crude ricinine) once a day for eight consecutive weeks to study its chronic toxicity. Urine, serum and kidney samples were collected and subjected to ¹H NMR metabolomics analysis. This approach, complemented by histopathological inspection and a biochemical assay, demonstrated that crude ricinine produced obvious nephrotoxicity and severe metabolic alterations in rats. These changes were related with oxidative stress, energy metabolism, amino acid metabolism, renal function and the gut bacteria system. This work provides a molecular basis for the chronic toxicity of crude ricinine and shows the power of a ¹H NMR-based metabolomic approach to study the toxicity of drugs dynamically and systematically.