FDA-approved antidepressants can relieve common side effects of cancer treatments

Researchers in China discovered that inhibiting a protein called GABAa The receptors can protect intestinal stem cells from the toxic effects of chemotherapy and radiotherapy. The study, published on September 20 in Journal of Experimental Medicine (JEM), indicates that the FDA-approved analgesic drug flumazenil, which targets GABAa Receptor, it can relieve some common gastrointestinal side effects, such as diarrhea and vomiting, caused by many cancer treatments.

Because they have to constantly multiply and replace cells lining the intestinal wall, intestinal stem cells are very sensitive to chemotherapy and radiotherapy. These therapies destroy the DNA of the intestinal stem cells and cause them to die, resulting in infection of the intestine and a variety of painful gastrointestinal symptoms. These toxic side effects, which can persist long after treatment ends, limit the dose of medication or radiation that can be given to cancer patients and lead to a deterioration in their quality of life.

A research team led by Dawei Chen and Jingxin Li at Qilu Medical School, Shandong University, discovered that levels of a protein called GABRA1 increase in the intestinal stem cells of mice treated with either radiation or chemotherapy drugs. GABRA1 is a component of GABAa The receptor, which is best known for its role in the nervous system, binds to the neurotransmitter g-aminobutyric acid (GABA). But Gabba and Gabbaa The receptors are also found in other tissues throughout the body.

The researchers found that inhibition of GABAa The receptor protects mice from the toxic side effects of chemotherapy or radiation, reducing the amount of DNA damage and increasing the survival of intestinal stem cells. This enabled the mice to maintain their normal intestinal lining and survive with lethal doses of radiotherapy or chemotherapy drugs.

Chen and colleagues found that inhibition of GABAa The receptor protects intestinal stem cells from DNA damage by limiting the formation of free radicals in response to radiochemotherapy. Crucially, however, researchers have determined that inhibition of GABAa The receptors do not prevent radiation therapy or chemotherapy drugs from killing cancer cells.

cheap flumazenil GABAa FDA-approved receptor blockers for the treatment of benzodiazepine overdoses and reversible sedation. Chen and colleagues found that flumazenil was also able to protect the intestines of mice from the toxic effects of radiochemotherapy. Furthermore, flumazenil also protects human colonic organoids-; miniature organs grown in the lab from stem cells of the human colon; From chemotherapy drugs and irradiation.

Taken together, our data indicate inhibition of GABAa The future is a promising strategy to specifically protect the intestine from radiochemotherapy. Future studies are needed to investigate the pharmacodynamics and tolerability of flumazenil in cancer patients undergoing treatment in the clinic.”

Dawei Chen, Qilu Medical College, Shandong University

source:

Journal reference:

Chang, C., et al. (2022) Inhibition of GABAA receptors in chemotherapy-induced enterotoxigenic dendritic cells. Journal of Experimental Medicine. doi.org/10.1084/jem.20220541.