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Objectives: Ovarian torsion is an important gynaecological emergency because it causes ischemia in ovary. Our aim is to research the effects of Hypericum perforatum on p53, TNF-α, CAT, SOD, GSH, PTEN and is haPI3K/Akt/mTOR pathway in ovarian of rats with ischemia reperfusion (I/R) injury. Materials and Methods: The study included 56 adult female rats which were allocated to 7 groups; control, ischemia, ischemia 300HP, ischemia 600HP, I/R, I/R 300HP and I/R 600HP. H. perforatum was applied to ischemia 300HP, ischemia 600HP, I/R 300HP and I/R 600HP groups at the dose of 300 mg/kg or 600 mg/kg by oral gavage. Collected ovarian tissues were examined by light microscopy, biochemical and real-time PCR techniques. Results: In histological examination, the least degeneration was seen in 600HP group among other groups, apart from control group. TUNEL results showed that apoptosis level of other groups was lower than that of ischemia and I/R groups. CAT and GSH levels of I/R 600HP group increased. The highest level of PTEN and mTOR was found in the ischemia group. The Akt level was lower in I/R and I/R 300HP groups but its level was close to that of control and I/R 600HP groups. TNF-α and p53 mRNA expressions in I/R group were increased. Conclusions: The result of the study showed that H. perforatum (600 mg/kg) had an effect on tissue degeneration, CAT and GSH levels, and also TNF-α and p53 mRNA expressions levels. We suggest that H. perforatum can be considered as an agent to protect against tissues damage during ischemia reperfusion. [ABSTRACT FROM AUTHOR]