Ivermectin mitigates 7,12-dimethylbenz(a) anthracene-induced reproductive toxicity in female wistar rats: An...

7,12-dimethylbenz(a)anthracene (DMBA) is a pervasive environmental polycyclic aromatic hydrocarbon that exerts genotoxic and endocrine-disrupting effects in female reproductive tissues, largely through oxidative stress and induction of apoptosis. Ivermectin, a food and drug administration-approved antiparasitic agent, has emerging anti-inflammatory and antioxidant properties.

We evaluated whether Ivermectin could protect the ovarian and uterine tissues against DMBA-induced injury.

In this experimental study, 20 female Wistar rats (8 wk, 210 $\pm$ 5 gr) were divided into 4 groups (n = 5/each): control, Ivermectin (1 mg/kg), DMBA (single 80 mg/kg dose), and DMBA + Ivermectin (same dosage). After 8 wk, sex hormones (estradiol, progesterone, testosterone) were measured by enzyme-linked immunosorbent assay. Oxidative stress markers (malondialdehyde, superoxide dismutase activity, and total antioxidant capacity) were assayed. Ovarian tissue was analyzed for apoptosis-related gene expression (Bax, Bcl-2, Caspase-3, p53), and uterine and ovarian tissues were evaluated for histopathological changes by hematoxylin and eosin staining.

Our findings showed that DMBA induced significant oxidative stress and tissue damage, along with hormone disruption and upregulation of pro-apoptotic genes. In contrast, Ivermectin co-treatment largely reversed these changes, such as reducing the serum malondialdehyde and increasing superoxide dismutase and total antioxidant capacity. Moreover, the hormone level balance significantly shifted toward control values. Histopathological examination showed DMBA-induced ovarian damage and uterine epithelial degeneration, which were attenuated by Ivermectin.

Ivermectin significantly ameliorated DMBA-induced oxidative damage, endocrine disruption, and apoptotic signaling in female rats. These findings suggest Ivermectin's potential for protecting the reproductive tissues from environmental toxin injury.