Green tea compound EGCG shields brain and kidneys from last-resort antibiotic colistin's toxic side effects
In mice and neuron cultures, green tea's EGCG curbed colistin's kidney and brain damage by protecting mitochondria and cutting oxidative stress.
Summary
Colistin is a last-resort antibiotic for multidrug-resistant bacterial infections, but its kidney and nervous system toxicity limits its use. Researchers screened five antioxidant, mitochondria-protecting compounds in primary neuron cultures exposed to colistin. Epigallocatechin-3-gallate (EGCG), the major green tea catechin, performed best. In a mouse model of colistin toxicity, EGCG pretreatment prevented weight loss, kidney tubular cell death, and motor impairment while preserving muscle strength. In the brain, EGCG maintained dendritic spine density, lowered caspase-3 activity (an apoptosis marker), and reduced astrogliosis. In neurons, it lowered reactive oxygen species and preserved mitochondrial membrane potential. Behavioral tests showed better recognition memory and less anxiety- and depressive-like behavior. The authors suggest EGCG could be a safe adjuvant that widens the therapeutic window of polymyxin antibiotics, though this evidence is preclinical and has not been tested in patients.
Detailed Summary
Colistin, a polymyxin antibiotic, is often the last option against multidrug-resistant Gram-negative infections. Its use is constrained by kidney and nervous system toxicity, which is linked to oxidative stress and mitochondrial dysfunction. Few strategies exist to protect the central nervous system during treatment, so a protective co-therapy would be clinically valuable.
The team screened five natural bioactive molecules with antioxidant and mitochondria-stabilizing properties in primary neuronal cultures exposed to colistin. EGCG, the main polyphenol in green tea, was the most effective. They then tested it in a mouse model of colistin toxicity, using molecular, histopathological, and behavioral readouts.
EGCG pretreatment prevented colistin-induced weight loss, renal tubular apoptosis, and neuromotor impairment, and preserved muscle strength. In the central nervous system, it maintained dendritic spine density, reduced caspase-3 activity, and attenuated astrogliosis. In vitro, protection was associated with lower reactive oxygen species and preserved mitochondrial membrane potential. Behavioral testing showed improved recognition memory and reduced anxiety- and depressive-like behaviors.
The authors conclude that EGCG offers broad neuro- and nephroprotection and could serve as an adjuvant to extend the therapeutic window of polymyxins. The mitochondrial and antioxidant mechanism also fits broader interest in mitochondrial health and stress resilience.
Important caveats apply. The work is preclinical, based on neuron cultures and mice. Based on the abstract, EGCG was given as pretreatment, which may not reflect real clinical timing. The abstract does not report doses, sample sizes, or whether EGCG affects colistin's antibacterial activity, which is essential before any clinical use. The mechanistic data come from in vitro work, so causality in vivo remains inferred. Human trials would be needed, and people should not self-medicate with green tea extracts during antibiotic therapy.
Key Findings
- EGCG ranked best among five antioxidant, mitochondria-stabilizing compounds screened in colistin-exposed primary neurons.
- In mice, EGCG pretreatment prevented colistin-induced weight loss, renal tubular apoptosis, and neuromotor impairment while preserving muscle strength.
- EGCG maintained dendritic spine density, reduced caspase-3 activity, and attenuated astrogliosis in the central nervous system.
- In vitro, protection coincided with lower reactive oxygen species and preserved mitochondrial membrane potential.
- EGCG improved recognition memory and reduced anxiety- and depressive-like behaviors in colistin-treated mice.
Methodology
Five candidate compounds were screened in primary neuronal cultures exposed to colistin, and EGCG was then tested in a mouse model of colistin toxicity. Outcomes included molecular, histopathological, and behavioral assessments, plus in vitro measures of reactive oxygen species and mitochondrial membrane potential.
Study Limitations
The evidence is preclinical (cultured neurons and mice), and the abstract gives no doses, sample sizes, or statistics. It does not state whether EGCG preserves colistin's antibacterial efficacy, and pretreatment may not match real-world use. Mechanistic findings were from in vitro experiments, and only the abstract was available for this summary.
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