L-Theanine Ameliorates Doxorubicin-Induced Ovarian Toxicity by Reducing Endoplasmic Reticulum Stress

Doxorubicin (DOX) is an anthracycline antibiotic widely used as an antineoplastic agent. L-theanine (LTN) is a unique amino acid obtained from tea (Camellia sinensis) and a highly valuable nutraceutical additive in the food industry. The aim of this study was to investigate the effects of LTN on ovarian endoplasmic reticulum stress (ERS) in DOX-induced rats. The rats were divided into one of four groups: Control (saline), DOX (20 mg/kg DOX, i.p.), DOX + LTN200 (DOX + 200 mg/kg LTN) and DOX + LTN400 (DOX + 400 mg/kg LTN). DOX was administered on the first day, followed by three consecutive days of LTN via oral gavage. The levels of ERS (GRP78, IRE1, and CHOP), oxidative stress (TOS, OSI, and MDA), inflammation (TNF-α) and fertility (E2 and PGN) parameters were analyzed using ELISA or assay kits. In addition, morphological and apoptotic (DNA fragmentation) changes in ovarian tissues were examined histologically. The study found that both doses of LTN were effective in reversing DOX-induced ERS by lowering oxidative stress, inflammation, and apoptosis, and alleviating morphological changes. However, the 400 mg/kg LTN group exhibited more significant effects. LTN treatment thus has the potential to alleviate the adverse effects on ovarian tissue caused by DOX by modulating the endoplasmic reticulum (ER) stress response and associated conditions.