Does ozone administration have a protective or therapeutic effect against radiotherapy‑induced testicular injury?

Background

Radiotherapy is a core treatment for many pelvic and abdominal cancers, but scattered radiation can reach nearby healthy tissue, including the testes. This can trigger oxidative stress - an imbalance between damaging free radicals and the body's natural antioxidant defences - leading to reduced sperm production and testicular tissue damage. Researchers investigated whether ozone therapy, already studied for its antioxidant-modulating effects, could protect against or help repair this type of radiation-induced testicular injury.

Study design

The study used 30 healthy adult male rats, divided evenly into five groups of six. One group received oxygen only (control), one received ozone therapy alone, one received radiotherapy alone, one received radiotherapy followed by ozone therapy, and one received ozone therapy followed by radiotherapy. Radiation was delivered to the scrotal region using a Cobalt-60 source, given as daily fractions over five days to a total dose of 20 Gray. Ozone therapy consisted of an ozone-oxygen gas mixture injected into the abdominal cavity once daily for three consecutive days, timed either before or after the radiation course depending on the group. Researchers then assessed testicular weight, a histological spermatogenesis score (the Johnsen score, based on tissue samples from each testis), and several biochemical markers of oxidative stress and antioxidant activity in blood and tissue samples.

Findings

Radiotherapy alone significantly reduced testicular weight and spermatogenesis scores compared with the control group, and significantly raised markers of oxidative damage while lowering the body's antioxidant enzyme levels. In contrast, the groups that received ozone therapy - whether before or after radiation - showed testicular weight, spermatogenesis scores, and oxidative stress markers that were close to those of the untreated control group, and significantly better than the radiotherapy-only group. The order in which ozone was given relative to radiation did not appear to change the outcome meaningfully.

What the authors concluded

The study authors concluded that ozone therapy appeared to be both protective and therapeutic against radiation-induced testicular damage in this rat model, and suggested it may hold potential benefit for patients undergoing radiotherapy. They noted that further research would be needed before moving from animal studies to human clinical trials.

Limitations of this study

This was a small preclinical study using only six animals per group, which limits how confidently the results can be generalised. The authors themselves noted that tissue damage was not evaluated as thoroughly as it could have been, and that the underlying molecular mechanism by which ozone might protect or repair radiation-induced testicular damage has not yet been established in the scientific literature. The radiation and ozone dosing schedules used were fixed experimental protocols that may not directly reflect real-world clinical radiotherapy regimens, and no long-term fertility or reproductive outcomes were measured. This study concerns radiotherapy-induced testicular injury in an animal model. It does not establish ozone as a treatment or cure for cancer itself. Ozone therapy is a complementary approach and should always be discussed with your oncology team.