Toxicity induced by orellanine from the mushroom Cortinarius orellanus in primary renal tubular proximal epithelial cells (RPTEC): Novel mechanisms of action

Abstract

The toxicity of Orellanine (OR), a significant factor in mushroom poisoning, has severe effects on the kidneys, particularly the proximal tubules. This study investigated the acute toxicity of OR from the Cortinarius orellanus mushroom in human Primary Renal Tubular Proximal Epithelial Cells (RPTEC). Additionally, the half maximal inhibitory concentration (IC50) of OR in MCF-7 cells was established. RPTEC were subjected to a 6.25 μg/ml dose of orellanine for 24 h, while Control cells were exposed to 0.05% DMSO (vehicle). The RT2 Profiler™ PCR Array Human Nephrotoxicity was utilized to identify genes that were upregulated or downregulated. Western blotting confirmed the protein product of some significantly regulated genes compared to control cells. The IC50 of OR was found to be 319.2 μg/ml. The mechanism of OR toxicity involved several pathways including apoptosis, metal ion binding, cell proliferation, tissue remodeling, xenobiotic metabolism, transporters, extracellular matrix molecules, and cytoskeleton pathways. Other genes from non-specific pathways were also identified. These findings enhance our understanding of OR nephrotoxicity and pave the way for future research into potential treatments or antidotes for natural mushroom poisoning.