Gd-DTPA-induced dynamic metabonomic changes in rat biofluids

Area of Science:

• Metabolomics
• Toxicology
• Nephrology

Background:

• Gadolinium-based contrast agents (GBCAs) like gadopentetate dimeglumine (Gd-DTPA) are widely used in medical imaging.
• Nephrogenic systemic fibrosis (NSF) is a serious condition associated with GBCAs, particularly in patients with renal impairment.
• Understanding the early metabolic disturbances caused by Gd-DTPA is crucial for elucidating NSF pathogenesis.

Purpose of the Study:

• To detect dynamic metabonomic changes induced by gadopentetate dimeglumine (Gd-DTPA) administration in rats.
• To investigate potential metabolic disturbances linked to the early pathogenesis of nephrogenic systemic fibrosis (NSF).

Main Methods:

• Utilized a nuclear magnetic resonance (NMR)-based metabolomics approach.
• Analyzed urinary and serum samples from rats following a single tail vein injection of Gd-DTPA (2 and 5 mmol/kg body weight).
• Collected samples on days 1, 2, and 7 post-injection to track dynamic changes.

Main Results:

• Gd-DTPA induced systematic metabolic changes affecting lipid, glucose, TCA cycle, amino acid metabolism, and gut microbiota functions.
• Metabolic recovery was observed in both dosage groups, but higher doses (5 mmol/kg) resulted in prolonged effects.
• Hyperlipidemia was noted post-injection, with nicotinate potentially aiding lipid metabolism recovery; tyrosine, glutamate, and gut microbiota disturbances may link to NSF progression.

Conclusions:

• The study provides essential insights into the metabolic alterations caused by Gd-DTPA.
• Findings are significant for understanding early-stage NSF pathogenesis.
• Observed recovery patterns in rats may have implications for treating early-stage NSF.