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Esculeoside A alleviates reproductive toxicity in streptozotocin-diabetic rats' s model by activating Nrf2 signaling
Jozaa Z AlTamimi1, Nora A AlFaris1, Ghedeir M Alshammari2
1Department of Physical Sports Sciences, College of Education, Princess Nourah Bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia.
Abstract:
This examination studied if Esculeoside A (ESA) alleviates reproductive toxicity in a type 1 diabetes mellitus (T1DM) rat model and if activating Nrf2 underlies this protection. T1DM was established by a single injection of STZ. Aged-matched adult control and STZ-DM rats were administered either the vehicle (5% carboxymethyl cellulose) or ESA (100 mg/kg). An additional group [STZ-DM + ESA (100 mg) + brusatol (2 m/kg] was added. All treatments were conducted for 16 weeks. ESA failed to attenuate weight loss, hyperglycemia, and hypoinsulinemia but significantly attenuated the associated dyslipidemia in STZ-DM rats. In parallel, ESA also enhanced total sperm count, motility, survival, reduced head and tail sperm abnormalities, increased circulatory concentrations of follicular stimulating hormone (FSH), testosterone, and Luteinizing hormone (LH), and stimulated the testicular expression of several steroidogenic enzymes (StAR, CYP11A1, CYP17A1, 3β-HSD1) in STZ-DM rats. These observations were associated with a higher testicular increase in the transcription, protein levels, and nuclear activities of Nrf2 that coincided with a reduction in the total levels of MDA and keap1 and a significant increase in the total levels of some antioxidants such as HO-1, SOD, and GSH. In concomitance, ESA reduced the testicular mRNA and nuclear concentrations of NF-κB and depressed the levels of TNF-α and IL-6. Brusatol prevented all these protective effects of ESA. In conclusion, activation of Nrf2 triggers the protective potential of ESA against reproductive toxicity in STZ-DM rats.
Insights
Esculeoside A (ESA) protects against reproductive toxicity in type 1 diabetes mellitus (T1DM) rat models by activating Nrf2. This antioxidant pathway improves sperm parameters and hormone levels, counteracting diabetes-induced damage.
Area of Science:
- Endocrinology
- Reproductive Biology
- Toxicology
Background:
- Type 1 diabetes mellitus (T1DM) is associated with male reproductive toxicity.
- Oxidative stress and inflammation play key roles in diabetes-induced reproductive dysfunction.
- Nrf2 signaling is a critical regulator of cellular defense against oxidative stress.
Purpose of the Study:
- To investigate the protective effects of Esculeoside A (ESA) against reproductive toxicity in a type 1 diabetes mellitus (T1DM) rat model.
- To determine if the activation of Nuclear factor erythroid 2-related factor 2 (Nrf2) mediates the protective effects of ESA.
Main Methods:
- T1DM was induced in rats using streptozotocin (STZ).
- Rats were treated with vehicle, ESA, or ESA plus brusatol (an Nrf2 inhibitor) for 16 weeks.
- Reproductive parameters, hormone levels, steroidogenic enzyme expression, oxidative stress markers, and inflammatory cytokines were assessed.
Main Results:
- ESA attenuated dyslipidemia, improved sperm count, motility, and morphology, and normalized FSH, LH, and testosterone levels in STZ-DM rats.
- ESA increased testicular Nrf2 activity, antioxidant enzyme levels (HO-1, SOD, GSH), and decreased oxidative stress markers (MDA).
- ESA reduced testicular NF-κB, TNF-α, and IL-6 levels, while brusatol blocked these protective effects.
Conclusions:
- Esculeoside A (ESA) ameliorates reproductive toxicity in a type 1 diabetes mellitus (T1DM) rat model.
- The protective effects of ESA are mediated through the activation of the Nrf2 antioxidant pathway.
- ESA demonstrates potential as a therapeutic agent for managing diabetes-related reproductive complications.
