Esculeoside A alleviates reproductive toxicity in streptozotocin-diabetic rats' s model by activating Nrf2 signaling

Jozaa Z AlTamimi; Nora A AlFaris; Ghedeir M Alshammari; Reham I Alagal; Dalal H Aljabryn; Mohammed Abdo Yahya

doi:10.1016/j.sjbs.2023.103780

Esculeoside A alleviates reproductive toxicity in streptozotocin-diabetic rats' s model by activating Nrf2 signaling

Saudi J Biol Sci. 2023 Sep;30(9):103780. doi: 10.1016/j.sjbs.2023.103780. Epub 2023 Aug 18.

Authors

Jozaa Z AlTamimi¹, Nora A AlFaris¹, Ghedeir M Alshammari², Reham I Alagal³, Dalal H Aljabryn¹, Mohammed Abdo Yahya²

Affiliations

¹ Department of Physical Sports Sciences, College of Education, Princess Nourah Bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia.
² Department of Food Science and Nutrition, College of Food and Agricultural Sciences, King Saud University, P.O. Box 84428, Riyadh 11451, Saudi Arabia.
³ Department of Health Sciences, College of Health and Rehabilitation Sciences, 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.

Keywords: Esculeoside A; Nrf2; Oxidative stress; Sperm; T1DM; Testis.