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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Animals, Apoptosis, Cell Line, Tumor, Collagen, Connective Tissue Growth Factor, Drug Evaluation, Preclinical, Female, Fibrosis, HT29 Cells, HeLa Cells, Humans, Ileum, Immediate-Early Proteins, Intercellular Signaling Peptides and Proteins, Male, Mice, Mice, Nude, Pravastatin, Radiation Injuries, Experimental, Radiation-Protective Agents, Rats, Rats, Wistar.
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Is successful mitigation of delayed intestinal radiation injury using pravastatin associated with acute injury improvement or tumor protection? Context: To investigate whether pravastatin mitigates delayed radiation-induced enteropathy in rats, by focusing on the effects of pravastatin on acute cell death and fibrosis according to connective tissue growth factor (CTGF) expression and collagen inhibition. Mitigation of delayed radiation-induced enteropathy was investigated in rats using pravastatin administered in drinking water (30 mg/kg/day) 3 days before and 14 days after irradiation. The ileum was irradiated locally after surgical exteriorization (X-rays, 19 Gy). Acute apoptosis, acute and late histologic alterations, and late CTGF and collagen deposition were monitored by semiquantitative immunohistochemistry and colorimetric staining (6 h, 3 days, 14 days, 15 weeks, and 26 weeks after irradiation). Pravastatin antitumor action was studied in HT-29, HeLa, and PC-3 cells by clonogenic cell survival assays and tumor growth delay experiments. Pravastatin improved delayed radiation enteropathy in rats, whereas its benefit in acute and subacute injury remained limited (6 h, 3 days, and 14 days after irradiation). Delayed structural improvement was associated with decreased CTGF and collagen deposition but seemed unrelated to acute damage. Indeed, the early apoptotic index increased, and severe subacute structural damage occurred. Pravastatin elicited a differential effect, protecting normal intestine but not tumors from radiation injury.
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Pravastatin provides effective protection against delayed radiation enteropathy without interfering with the primary antitumor action of radiotherapy, suggesting that clinical transfer is feasible. Final Decision: no