The role of adenosine triphosphate in the treatment of linezolid-induced ovarian damage and reproductive dysfunction in rats: An investigation into the pathogenesis

Linezolid is an oxazolidinone-derived antibacterial agent that inhibits bacterial protein synthesis by binding to the peptidyl transferase center of the 50S ribosomal subunit. This study investigated whether exogenously administered adenosine triphosphate (ATP) mitigates ovarian damage and reproductive dysfunction induced by linezolid in rats. Forty-eight female albino Wistar rats were randomly assigned to four groups (n = 12 each): healthy control (HG), ATP-only (ATPG), linezolid-only (LZDG), and ATP plus linezolid (ATLDG). ATPG and ATLDG received intraperitoneal ATP (4 mg/kg), whereas HG and LZDG received saline (0.9 % NaCl). One hour later, linezolid (125 mg/kg) was administered orally to LZDG and ATLDG, and the regimen was repeated twice daily for 28 consecutive days. At study end, six rats per group were euthanized for ovarian biochemical, histopathological, and immunohistochemical evaluations; prior to euthanasia (i.p. thiopental sodium, 50 mg/kg), blood was collected for serum prolactin and anti-Müllerian hormone (AMH) analysis. For fertility assessment, the remaining six females per group were co-housed with two proven fertile males for seven days and then monitored for pregnancy for one month. Linezolid exposure increased oxidative stress, caused ovarian tissue injury, decreased AMH, elevated prolactin, and resulted in a 66.7 % infertility rate. ATP co-treatment attenuated these alterations and reduced infertility to 33.3 %. These findings suggest that ATP may provide a protective therapeutic approach against linezolid-induced ovarian toxicity and reproductive dysfunction. © 2026 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.