Spirulina sp. attenuates doxorubicin-induced uterine injury in female rats: Histological and molecular evaluation

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Background Doxorubicin (DOX) is an effective anthracycline chemotherapeutic agent; however, its use may cause reproductive tissue toxicity. This study investigated the protective effects of Spirulina sp. (SP) against DOX-induced uterine injury in female rats. Methods Female Wistar albino rats (n=24) were divided into control, DOX, DOX+SP, and SP groups. DOX was administered intraperitoneally at 2 mg/kg every three days for six, while SP was given orally at 500 mg/kg/day for 21 days. Uterine histology and HIF-1α/GSK-3β immunoreactivity were evaluated, oxidative stress was assessed using MDA, SOD, and GPx, and BAX, BCL2, and CASP3 expression was analyzed by qRT-PCR. Results DOX caused marked uterine histopathological damage and reduced uterine wall thickness from 540.6±109.4 to 258.32±80.2 µm (p=0.001), whereas SP co-treatment increased it to 384±88.6 µm (p=0.002 vs. DOX). DOX increased MDA and reduced SOD and GPx activities, while SP attenuated these oxidative alterations. DOX also increased BAX and CASP3 and decreased BCL2 expression, whereas SP shifted the apoptotic profile toward control levels. Increased HIF-1α and reduced GSK-3β immunoreactivity following DOX were also ameliorated by SP. Bioinformatics predictions highlighted oxidative stress, apoptosis, hypoxia-related signaling, and PI3K/AKT/GSK-3β-associated pathways. Conclusions Collectively, these findings suggest that Spirulina sp. administration may attenuate DOX-associated uterine tissue alterations, potentially through modulation of oxidative stress, apoptosis, and hypoxia-related signaling. However, the present findings do not establish a direct protective effect of Spirulina sp. on the uterus, and further studies are warranted to clarify the underlying mechanisms and determine whether these effects translate into functional reproductive benefits.