Astaxanthin- Enriched Fraction from the Microalga Haematococcus pluvialis Mitigates Kidney Injury via Modulation of Nrf2/Keap1 and MAPK/ERK Pathways in Rats

Abstract

Acute kidney injury is a complication of using gentamicin in high doses and is associated with severe morbidity and mortality. Astaxanthin, the red xanthophyll carotenoid pigment, has an antioxidant power higher than 100 times that of vitamin E and 10 times more than that of β-carotene, making it one of the strongest bioactive carotenoids. Haematococcus pluvialis, Haematococcaceae, microalga produces high amounts of astaxanthin in the form of astaxanthin esters besides adequate amounts of free astaxanthin. We attempted to explore the potential therapeutic effects of astaxanthin- and astaxanthin ester–enriched fractions from H. pluvialis against acute kidney injury induced by gentamicin and their mechanisms of action in rats. Adult male Wister albino rats were injected with gentamicin (100 mg/kg, i.p.) for seven consecutive days to induce acute kidney injury, and these rats were treated daily with astaxanthin ester–enriched fractions (30 mg/kg; p.o.) for 14 days. LC/ESI–MS analysis revealed the presence of different isomers of free astaxanthin, astaxanthin monoesters, and astaxanthin diesters in the astaxanthin- and astaxanthin ester–enriched fractions. Astaxanthin and its esters ameliorated kidney dysfunction, modulated nuclear factor erythroid 2 related factor 2/Kelch-like erythroid associated protein 1/hypoxia-inducible factor-alpha, and suppressed mitogen-activated protein kinases/extracellular signal-regulated kinases/renin-angiotensin system expression. Astaxanthin and its ester improved early acute kidney injury via modulation of the Nrf2/Keap1 antioxidant defense pathway and MAPK/ERK signaling cascade. Graphical Abstract: [Figure not available: see fulltext.].