Modulation of Antioxidant and Anti-Inflammatory Response in the Eyes of CKD Animals Supplemented with Larch Arabinogalactan

Abstract

Chronic kidney disease (CKD) is a systemic condition associated with inflammation and oxidative stress, affecting organs beyond the kidneys. Although rarely emphasized, the eyes may also be affected but underlying molecular mechanisms remain largely unexplored. The gut–kidney and gut–eye axes are emerging as therapeutic targets with prebiotics like ResistAid®-a Larch Arabinogalactan (LAG) supplement with antioxidant and immunomodulatory effects—showing promise through gut microbiota modulation. This study assessed ResistAid®’s effects on ocular gene expression in a CKD rat model. Twenty four Wistar rats were assigned to Sham (S), Sham + Treatment (ST), Nephrectomized (N), Nephrectomized + Treatment (NT) (n = 6 each). CKD was induced by 5/6 nephrectomy. The treatment was administered via gavage for 30 days at a dose of 5.35 mg/day, adapted from human recommendations. At day 30, blood and tissues were collected. Expression of antioxidant enzymes (Cat, Sod1, Gpx1, Gpx4) and other genes (Nfe2l2, Nfκb1, Timp3, Hif-1α, Kim1, Klotho) was analyzed by qPCR. Biochemical and well-being assessments were also conducted. Nephrectomy, regardless of treatment, increased Sod1 and Hif1ɑ expression in eye and blood; Specific to NT animals, ocular Gpx1, Gpx4 and Nfe2l2 expressions were markedly elevated when compared with N animals and blood Kim1 and ocular Nfκb1 expressions were not elevated, differing from N animals. No significant changes were observed between the S and ST groups. CKD induces systemic oxidative and inflammatory responses. ResistAid® partially mitigated these effects in blood and eye, suggesting systemic and local benefits, possibly via gut microbiota modulation.