Researchers from China have suggested that Flumazenil, a selective GABAA receptor antagonist administered via injection, is a possible route to protecting the gut wall and microbiome from chemotherapy or radiotherapy damage.
One of the biggest concerns when having chemo or radiotherapy is the damage to the microbiome (and specifically the bacteria in the gut lining and gut wall). The gut lining is a major factor in the immune response; and damage leaves cancer patients with less of an attack system towards their cancer. Damage to the gut wall can cause gastrointestinal problems and nausea.
Worse, the chemoradiotherapy can also trigger DNA damage and induce P53-dependent apoptosis in the intestinal stem cells of the gut wall, because they are constantly dividing and replacing themselves.
Researchers from China may have found a solution having shown that a protein, the GABAA receptor, protects the gut lining from this toxicity. The team observed increases in the receptor levels, But when the researchers applied the receptor inhibitor, bicuculline, the damage ceased. The nearest drug to this is Flumazenil. Flumazenil is a selective GABAA receptor antagonist administered via injection,It was first marketed in 1987 by Hoffmann-La Roche under the trade name Anexate.
“Taken together, our data suggest that inhibiting the GABAA receptor is a promising strategy to specifically protect the intestine from chemoradiotherapy,” explained Dawei Chen, a researcher at Cheeloo College of Medicine, Shandong University in China in the press release. Next they will look at the human response rather than mice.
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References
- Inhibition of GABAA receptors in intestinal stem cells prevents chemoradiotherapy-induced intestinal toxicity; Journal of Experimental Medicine; Volume 219, Issue 12; 20 Sept 2022