Co-administration of Spirulina and L-carnitine preserves ovarian reserve in a rat model of premature ovarian insufficiency via SIRT1 regulation of oxidative stress, inflammation, and apoptosis

Abstract

Abstract This study aimed to assess the possible consequences of spirulina (SP) and/or L-carnitine (L-car) on the prevention of primordial follicular reserve depletion and the preservation of ovarian follicular structure and function in a rat model of premature ovarian insufficiency (POI). Forty healthy adult female Sprague-Dawley albino rats were randomly assigned into five equal-sized groups (n = 8): normal control, DOX group (2.5 mg/kg i.p.), SP group (500 mg/kg intragastric), L-car group (250 mg/kg i.p.), and SP + L-car group in the same previous doses. In comparison to the DOX group, administration of either SP or L-car significantly increased serum E2 and AMH levels along with a significant decrease in the FSH and LH levels (p < 0.05). The oxidative stress was significantly reduced. Ovarian expressions of NF-κB, iNOS, FOXO1, P53, and caspase-3 decreased significantly, while SIRT1, STAR, CYP17A1, HSD17B3, Nrf2, and mtDNA increased significantly. Histology revealed histoarchitecture improvement as the mean % of atretic follicles and degenerated corpora lutea was significantly reduced (p < 0.05). The combined treatments synergistically improved the parameters studied more than either treatment alone. The molecular docking results revealed the ability of both n-hexadecanoic acid and L-carnitine to activate SIRT1 and subsequent antioxidant, anti-inflammatory, and anti-apoptotic pathways. This ovoprotective effect is suggested to be mediated through activation of different SIRT1-mediated protective signaling pathways that remodel ovarian redox status, inflammation, and apoptosis, which may strengthen the potential role of SP and L-car as a chemotherapy adjuvant, reducing the negative health effects of early menopause after cancer therapy.