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Updated: Aug 16, 2025
Culture and Co-Culture of Mouse Ovaries and Ovarian Follicles
Published on: March 17, 2015
Protective effect of gallic acid on doxorubicin-induced ovarian toxicity in mouse
Regina Lucia Dos Santos Silva1, Thae Lanne Barbosa Gama Lins1, Alane Pains Oliveira do Monte1
1Nucleus of Biotechnology Applied to Ovarian Follicle Development, Federal University of São Francisco Valley, Petrolina 56300-990, PE, Brazil.
Abstract:
The aims of the present study were to evaluate the protective effects of gallic acid against doxorubicin-induced ovarian toxicity in mice, and to verify the possible involvement of PI3K and mTOR signaling pathway members (PTEN, Akt, FOXO3a and rpS6) in the gallic acid protective actions. Mice were pretreated with NaCl (0.15 M, p.o.) (control and doxorubicin groups) or gallic acid (50, 100 or 200 mg/kg body weight, p.o.) once daily, for 5 days, and on the third day of treatment, after 1 h of treatment administration, the mice received saline solution (i.p.) (control group) or doxorubicin (10 mg/kg of body weight, i.p.). Next, the ovaries were harvested for histological (follicular morphology and activation), fluorescence (GSH and mitochondrial activity), and immunohistochemical (PCNA, cleaved caspase-3, TNF-α, p-PTEN, Akt, p-Akt, p-rpS6 and p-FOXO3a) analyses. The results showed that cotreatment with 50 mg/kg gallic acid plus doxorubicin preserved the percentage of normal follicles and cell proliferation, reduced the percentage of cleaved caspase-3 follicles, prevented inflammation, and increased GSH concentrations and mitochondrial activity compared to doxorubicin treatment alone. Furthermore, cotreatment 50 mg/kg gallic acid plus doxorrubicin increased expression of Akt, p-Akt, p-rpS6 and p-FOXO3a compared to the doxorubicin alone. In conclusion, 50 mg/kg gallic acid protects the mouse ovary against doxorubicin-induced damage by improving GSH concentrations and mitochondrial activity and cellular proliferation, inhibiting inflammation and apoptosis, and regulating PI3K and mTOR signaling pathway.
Insights
Gallic acid (50 mg/kg) protects mouse ovaries from doxorubicin toxicity by enhancing antioxidant levels, mitochondrial function, and cell proliferation while reducing inflammation and apoptosis, involving PI3K/mTOR pathways.
Area of Science:
- Reproductive Toxicology
- Pharmacology
- Cellular Biology
Background:
- Doxorubicin is a potent chemotherapy agent with known ovarian toxicity.
- Ovarian damage can lead to infertility and other reproductive health issues.
- Gallic acid, a natural phenolic compound, has demonstrated antioxidant and anti-inflammatory properties.
Purpose of the Study:
- To investigate the protective effects of gallic acid against doxorubicin-induced ovarian toxicity in mice.
- To elucidate the role of the PI3K/mTOR signaling pathway (PTEN, Akt, FOXO3a, rpS6) in gallic acid's protective mechanisms.
Main Methods:
- Mice were pretreated with gallic acid (50, 100, or 200 mg/kg) or NaCl for 5 days.
- Doxorubicin (10 mg/kg) was administered intraperitoneally on day 3.
- Ovaries were analyzed using histological, fluorescence, and immunohistochemical techniques.
Main Results:
- Gallic acid (50 mg/kg) preserved normal follicle morphology and cell proliferation.
- It reduced apoptosis (cleaved caspase-3), inflammation (TNF-α), and increased GSH and mitochondrial activity.
- Gallic acid upregulated Akt, p-Akt, p-rpS6, and p-FOXO3a expression, indicating PI3K/mTOR pathway activation.
Conclusions:
- Gallic acid (50 mg/kg) effectively protects against doxorubicin-induced ovarian damage.
- Protection is mediated by improved antioxidant status, mitochondrial function, and cell proliferation.
- The findings highlight the involvement of the PI3K/mTOR signaling pathway in gallic acid's protective effects.
