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

Abstract

L-Theanine is the most abundant free amino acid present in tea. Several tea components have been studied for their impact on male fertility, but little is known about the effects of L-theanine. Cyclophosphamide (CP) is an antineoplastic and immunosuppressive agent that reduces fertility in males. In the present study, we evaluated the effect of L-theanine on CP-induced testicular toxicity in male mice. A single dosage of 50 mg/kg saline or CP was administered intraperitoneally over the course of 5 days. Mice were administered L-theanine (80 mg/kg) or saline by gavage for 30 days. Animals were euthanized 24 h after the last Ltheanine administration, and the testes were removed for histopathological and transmission electron microscopy analysis. Histological evaluation and transmission electron microscopy showed that administration of L-theanine alleviated CP-induced damage to the testicles, including spermatogonial cells, epithelial cells, seminiferous tubules, and basement membrane. An integrated proteomics and metabolomics investigation of testes revealed that L-theanine therapy substantially affected the quantity of 719 proteins (395 upregulated and 324 downregulated) and 196 metabolites (75 upregulated and 111 downregulated). The top three enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways for these proteins and metabolites were purine metabolism, choline metabolism in cancer, and arachidonic acid metabolism. This is the first study to reveal the protective effect of L-theanine on CP-induced testicular toxicity. L-Theanine could be a potential natural active substance for resistance to the testis toxicity induced by CP.

Protective effects of l-theanine and dihydromyricetin on reproductive function in male mice under heat stress

“…37–40 Additionally, chemotherapy-treated mice administered with LTA showed an increased body weight, testicular organ index, and serum testosterone levels. 44 This indicates that LTA may enhance testicular injury recovery and modulate reproductive function. However, the protective effects of LTA and DHM against reproductive function impairment induced by heat stress remain to be elucidated.…”

Benefits of l-theanine supplementation and its possible role in clinical use – review

“…5 days of pretreatment with the amino acid resulted in reduction of testicular damage concerning spermatogonial cells, epithelial cells, seminiferous tubules and basement membrane. [34]…”

Protective effect of coenzyme Q10 in cyclophosphamide-induced kidney damage in rats

“…Stankiewicz et al, reported that oxidative stress and elevated reactive oxygen species (ROS) could play an important role in cyclophosphamide-induced kidney damage 3 . Furthermore, prior studies demonstrated that cyclophosphamide could inhibit the activities of antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT) 4,5 . Other theories related to nephrotoxicity due to cyclophosphamide were imbalance of the oxidants-antioxidants system, increase of the inflammatory cytokines, and apoptosis 6 , although there is no consensus that, to prevent the toxicity due to cyclophosphamide, a potent antioxidant agent could be useful.…”