Pravastatin Attenuates Acute Radiation-Induced Enteropathy and Improves Epithelial Cell Function

Area of Science:

• Gastroenterology
• Radiation Oncology
• Pharmacology

Background:

• Radiation-induced enteropathy is a significant complication of abdominal radiation therapy, characterized by intestinal epithelial damage and impaired barrier function.
• Oxidative stress and inflammation are key contributors to the pathogenesis of radiation-induced enteropathy.
• Pravastatin, a statin drug, possesses known anti-inflammatory properties that may offer therapeutic benefits.

Purpose of the Study:

• To investigate the therapeutic efficacy of pravastatin in mitigating radiation-induced enteropathy.
• To evaluate the effects of pravastatin on intestinal epithelial cell proliferation, oxidative damage, and inflammatory responses in vitro and in vivo.

Main Methods:

• Utilized an irradiated human intestinal epithelial cell line (InEpC) to assess proliferation, senescence, oxidative damage, and cytokine expression.
• Employed a mouse model of radiation-induced enteropathy for histological analysis, bacterial translocation assays, intestinal permeability tests, and inflammatory cytokine assessment.
• Administered pravastatin to assess its protective and therapeutic effects on radiation-damaged intestinal tissues.

Main Results:

• Pravastatin treatment attenuated histological damage in irradiated mice, including villi shortening and crypt dysfunction, and normalized epithelial cell differentiation.
• In vitro and in vivo studies demonstrated that pravastatin enhanced intestinal epithelial cell proliferation and reduced radiation-induced oxidative damage.
• Pravastatin significantly inhibited pro-inflammatory cytokines (IL-6, IL-1β, TNF-α) in irradiated cells and rescued intestinal barrier dysfunction in mice via anti-inflammatory mechanisms.

Conclusions:

• Pravastatin exhibits significant therapeutic effects on intestinal lesions caused by radiation.
• The drug attenuates radiation-induced epithelial damage by effectively suppressing oxidative stress and inflammatory responses.
• Pravastatin represents a potential therapeutic agent for managing radiation-induced enteropathy.