Oxaloacetic Acid

The ecological risks of pyraclostrobin (PY) in the environment have become an increasing concern, yet its chronic toxicity and mechanism to aquatic organisms remain unclear. This study employed histopathological, metabolomic, and transcriptomic analyses to investigate the chronic effects of environmental concentrations of PY and underlying potential toxic mechanism in adult zebrafish. The result showed that 0.24 and 2.4 μg/L PY induced liver damage in zebrafish after 21 d exposure, with 0.24 μg/L PY elicited more pronounced transcriptional and metabolic alterations across diverse pathways in zebrafish liver. Mechanistic analyses showed that PY exposure could decrease the transcription of genes involved in pyrimidine and purine metabolism, thereby disrupting nucleotide synthesis, while simultaneously down-regulating the expression of multiple genes related to DNA replication processes and DNA repair system. Furthermore, PY perturbed hepatic glucolipid metabolism, evidenced by glycerophospholipid accumulation and decreased levels of glucose, pyruvate, triglyceride, cholesterol, and carbohydrates. The reduction in carbohydrates involved in ABC transporters, as well as the disruption in Abcb5, Abcc1, Abcd2, Abcd3 or Abcc10 transcription, suggested that ABC transporters might mediate PY-induced metabolic dysfunction. These findings provided mechanistic insights into PY-induced hepatotoxic effects in zebrafish, highlighting the need to address the chronic toxicity and ecological risks of environmental concentrations of PY for aquatic organisms.

Aging leads to deterioration of the liver and kidney. Metabolic research on aging organs, including liver and kidney and metabolic studies of caloric restriction (CR), which delay aging and extends lifespan, are not well understood. In this study, we monitored metabolic changes associated with aging and explored potential biomarkers in kidney and liver of young (Y, 8 months), old (O, 23 months), and old calorie-restricted (OCR, 23 months) rats by metabolic profiling of organic acids (OA), free fatty acids (FFA), amino acids (AA) using gas chromatography-tandem mass spectrometry. Optimization of OA, FFA, and AA profiling methods were useful for quantifying these metabolites in kidney and liver. Profile analysis identified 48 and 45 metabolites in the kidney and liver, respectively. In the kidney, malic acid was significantly higher when comparing the Y and O groups, whereas 3-hydroxybutyric acid was significantly higher when comparing the O and OCR groups. In the liver, four metabolites (phenylacetic acid, valine, isoleucine, and tyrosine) were significantly evaluated as potential biomarker when comparing the Y and O groups, whereas 3-hydroxybutyric acid was significantly increased when comparing the O and OCR groups. Metabolomics results indicate that aging leads to mitochondrial dysfunction, phenylalanine metabolism disorders, and kidney dysfunction, whereas CR may regulate renal aging by reducing oxidative stress, inflammation, and lipid accumulation, while improving energy metabolism and resistance to oxidative stress in the liver. This result may explain some changes in the metabolism of aged kidney and liver during aging and CR.