Protective Effect of l-Theanine on Cyclophosphamide-Induced Testicular Toxicity in Mice

l-Theanine is the most abundantfree amino acid presentin tea. Several tea components have been studied for their impacton male fertility, but little is known about the effects of l-theanine. Cyclophosphamide (CP) is an antineoplastic and immunosuppressiveagent that reduces fertility in males. In the present study, we evaluatedthe effect of l-theanine on CP-induced testicular toxicityin male mice. A single dosage of 50 mg/kg saline or CP was administeredintraperitoneally over the course of 5 days. Mice were administered l-theanine (80 mg/kg) or saline by gavage for 30 days. Animalswere euthanized 24 h after the last l-theanine administration,and the testes were removed for histopathological and transmissionelectron microscopy analysis. Histological evaluation and transmissionelectron microscopy showed that administration of l-theaninealleviated CP-induced damage to the testicles, including spermatogonialcells, epithelial cells, seminiferous tubules, and basement membrane.An integrated proteomics and metabolomics investigation of testesrevealed that l-theanine therapy substantially affected thequantity of 719 proteins (395 upregulated and 324 downregulated) and196 metabolites (75 upregulated and 111 downregulated). The top threeenriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways forthese proteins and metabolites were purine metabolism, choline metabolismin cancer, and arachidonic acid metabolism. This is the first studyto reveal the protective effect of l-theanine on CP-inducedtesticular toxicity. l-Theanine could be a potential naturalactive substance for resistance to the testis toxicity induced byCP.

Automated summary

This study evaluated the effects of the main amino acid theanine in tea on cyclophosphamide-induced testicular toxicity in male mice. The results showed that theanine could alleviate the damage to the testicles caused by cyclophosphamide and have impacts on multiple metabolic pathways and protein production.