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Melatonin Alleviates Atrazine-Induced Kidney Damage by Regulating RIPK3 to Inhibit Necroptosis
Qi-Qian Wang1, Mu-Zi Li1, Jing Lan1
1College of Veterinary Medicine, Northeast Agricultural University, 600 Changjiang Street Xiangfang District, Harbin 150030, P. R. China.
Journal of Agricultural and Food Chemistry
|May 12, 2026
Summary
Melatonin protects kidneys from the herbicide atrazine by inhibiting RIPK3-dependent necroptosis. This discovery offers a new therapeutic strategy for chemical-induced kidney damage.
Area of Science:
- Toxicology
- Molecular Biology
- Pharmacology
Background:
- Atrazine, a common herbicide, accumulates in kidney tissue, increasing nephrotoxicity risk.
- Melatonin, a hormone, shows potential renal protective effects, but its mechanisms are unclear.
Purpose of the Study:
- To investigate melatonin's protective role against atrazine-induced kidney injury.
- To elucidate the molecular mechanisms underlying melatonin's renoprotective effects.
Main Methods:
- Utilized in vivo and in vitro models to study atrazine-induced kidney damage.
- Employed molecular docking and dynamics simulations to explore melatonin-RIPK3 interactions.
- Performed RIPK3 knockdown experiments to validate its role.
Main Results:
- Atrazine exposure activates the RIPK1-RIPK3-MLKL pathway, causing renal cell necroptosis and inflammation.
- Melatonin treatment significantly reduced atrazine-induced kidney damage and inflammation.
- Melatonin potentially binds to RIPK3, inhibiting necroptosis signaling; RIPK3 is confirmed as a key mediator.
Conclusions:
- Melatonin mitigates atrazine-induced renal injury via RIPK3-dependent inhibition of necroptosis.
- This study reveals a novel mechanism for melatonin's renoprotective action.
- Melatonin shows promise as a therapeutic agent for chemical-induced nephrotoxicity.
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