Alterations in the testicular lipidome after tumor irradiation and their potential modulation by long-term losartan treatment

Irradiation of the testes can have adverse effects on their structure and function, potentially leading to infertility. Medications that can show antioxidant activity, such as losartan may mitigate the irradiation-related deleterious effects. The goal of this study was to evaluate the impact of irradiation on rat testes fatty acid (FA) and lipid profiles, as well as to assess the effectiveness of losartan in mitigating radiation-induced changes over 2-and 60-days.
Forty-six male Wistar rats were allocated into six groups: control (CTR2 and CTR60), irradiated (IR2 and IR60), and irradiated and treated with losartan (IRLOS2 and IRLOS60), euthanized 2- or 60-days post-irradiation to assess acute and late testicular effects. The FA and lipidome plasticity were evaluated by using gas chromatography-mass spectrometry and C18-liquid chromatography-mass spectrometry, respectively.
Groups irradiated after 60-days, without and with losartan, showed a significant decrease in testicular content in FA 16:0, FA 22:6 n-3 and FA 22:5 n-6. Changes in the testicular lipidome, particularly in lipid species belonging to triacylglycerols (TG) and phospholipid classes including phosphatidylcholine (PC), lysophosphatidylcholine (Lyso-PC), phosphatidylserine (PS), and cardiolipin (CL), were observed. TG species were downregulated in irradiated testicular samples, but losartan was able to prevent the downregulation of several TG species containing polyunsaturated fatty acids in testes irradiated after 60-days. After 60-days, several PC lipid species (vinyl-ether or ether-linked), endogenous antioxidants, were significantly increased in testicular tissues exposed to irradiation and losartan. However, the effect was less pronounced in the presence of losartan, suggesting the protective effect of the drug. Conversely, PS, lyso-PC, and CL levels were reduced in irradiated testes after 60-days but losartan could not mitigate those effects.
These lipidomic findings support previous morphological data indicating that losartan helps preserve testicular function, minimizing the effects of radiation.