Mancozeb induces nephrotoxicity by impairing the oxidative phosphorylation pathway: A transcriptome study

Area of Science:

• Toxicology
• Molecular Biology
• Biochemistry

Background:

• Mancozeb (MCZ) is a widely used fungicide.
• Understanding the molecular mechanisms of MCZ-induced kidney toxicity is crucial for risk assessment.

Purpose of the Study:

• To elucidate the underlying mechanism of mancozeb (MCZ)-induced kidney injury.
• To investigate the effects of MCZ exposure on kidney function, gene expression, and metabolic pathways in mice.

Main Methods:

• Mice were exposed to MCZ (100 mg/kg) or control (deionized water) for 30 days.
• Kidney function indicators, oxidative stress markers, transcriptome, and metabolome were analyzed.
• Gene expression was verified using PCR.

Main Results:

• MCZ exposure damaged kidney structure and significantly increased creatinine and uric acid levels.
• MCZ induced oxidative stress by increasing reactive oxygen species (ROS) and MDA, while decreasing SOD and GSH-PX.
• Transcriptome analysis revealed enrichment in the oxidative phosphorylation pathway, with specific gene expression changes (e.g., up-regulation of ndufs1, ndufab1; down-regulation of cox5b, ndufa5, ndufa6).
• Metabolomic analysis identified the cGMP-PKG signaling pathway and altered levels of Guanosine monophosphate and Adenosine 5'-monophosphate.

Conclusions:

• MCZ impairs kidney function in mice primarily by obstructing the oxidative phosphorylation pathway.
• This obstruction leads to increased oxidative stress and subsequent kidney injury.
• The findings provide insights into the molecular pathogenesis of MCZ nephrotoxicity.