Astaxanthin-Rich Algal Hepatic Modulation in D-Galactose-Induced Aging in Rats: Role of Nrf2.

Aging is associated with hepatic morphological and physiological deterioration due to the accumulation of endogenous and exogenous free radicals and the resultant oxidative stress. The present study aims to investigate the effect of Haematococcus pluvialis microalgae on hepatic changes associated with D-galactose (D-Gal)-induced aging in rats. Aging was induced in rats by daily intraperitoneal injection of D-Gal (200 mg/kg/day) for eight consecutive weeks. D-Gal-injected rats were treated by astaxanthin (ATX)-rich H. pluvialis biomass, its carotenoid and polar fractions for two weeks. Twenty four hours after the last dose, blood samples were collected and the liver tissues were isolated for further biochemical and histopathological examinations. D-Gal induced aging was associated with an elevation in serum liver function parameters, hepatic oxidative stress biomarkers viz., catalase (CAT), glutathione transferase (GST) and myeloperoxidase (MPO), as well as decreased expression of nuclear factor like-2 (Nrf2). Moreover, induction of aging exhibited an elevation of hepatic inflammatory cytokine; interleukin-6 (IL-6) and its modulator; nuclear factor Kappa B (NF-KB). However, treatment of D-Gal injected rats with ATX-rich H. pluvialis restored the serum liver function parameters as well as hepatic CAT, GST and MPO levels with an elevated expression of Nrf2. Treatment with ATX-rich H. pluvialis was also accompanied with a decrease in hepatic levels of NF-KB and IL-6. Histopathological examination emphasized all the previous results. Similarly, all trans-astaxanthin showed high affinity towards Nrf2 with -7.93 kcal/mol estimated free energy of binding as well as moderate affinities towards IL-6 and NF-KB through a docking study. ATX-rich H. pluvialis showed beneficial effects by ameliorating the hepatic changes associated with D-Gal induced aging in rats due to its modulatory role of the Nrf2/Keap pathway.