Serum and urine metabolomics analysis reveals the role of altered metabolites in patulin-induced nephrotoxicity. (June 2022) - Pal, Saurabh
Graphical abstract: Highlights: Low-dose sub-acute exposure toPAT caused nephrotoxicity in Wistar rats. Tubular nephrosis, cast and glycogen deposition observed in PAT treated rats kidney. Metabolomics revealed altered metabolites in urine and serum of PAT treated rats. The α-linolenic acid, indole, and indoleacrylic acid were common in serum and urine. Amino acid, fatty acid and TCA cycle was significantly affected in PAT treated rats. Abstract: Various studies have identified the kidney as a target organ for patulin (PAT)-induced toxicity. However, detailed mechanistic insights into PAT-induced nephrotoxicity had not yet been done. Therefore, along with classical toxicological parameters, liquid chromatography-high resolution massed spectrometry (LC-HRMS) based metabolomics has been carried out to delineate the mechanism(s) of PAT-induced nephrotoxicity. An in vivo study was conducted using male Wistar rats, divided into three groups. PAT (25 µg/kg b.wt and 100 µg/kg b.wt) and, control were given through oral gavage, 5 days/week for 28 days. At the end of the experiment, changes in the mean body/ organ weight, food and water intake, expression of marker proteins of kidney injury, and histopathological changes were investigated. Furthermore, using LC-HRMS based metabolomics was performed on the serum and urine of PAT-exposed rats. The histopathological and toxicological analysis revealed a significant increase in glomerular mesangial cells, vacuolar degeneration, and cast deposition in the proximal convoluted tubules. The metabolomics showed metabolic perturbations in amino and fatty acid-related metabolic pathways in serum and urine of PAT-treated rats. In conclusion this study expands our understanding of PAT-induced metabolic alterations and its effects on renal function.