Ameliorative effect of urolithin A on d-gal-induced liver and kidney damage in aging mice via its antioxidative, anti-inflammatory and antiapoptotic properties.

Urolithin A, a metabolite produced by human colon microflora from ellagic acid and related compounds, has been reported to have antioxidant, anti-inflammatory and antiapoptotic properties. The present study investigates the protective effects of urolithin A (Uro A) on d-galactose (d-gal)-induced liver and kidney injury and the possible mechanisms in mice. In this study, we first investigated the antioxidant ability of Uro A in vitro . Then mice were treated with d-gal subcutaneously (150 mg kg -1 d -1 ), followed by Uro A at different dosages (50, 100, 150 mg kg -1 d -1 , administered orally) for 8 weeks. The levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN) and creatinine (Cr) in the serum were tested. Histopathological features were assessed by hematoxylin and eosin (HE) staining followed by an assessment of the antioxidant and anti-inflammatory activities. Furthermore, we also evaluated the expression levels of the genes Bax, Bcl-2 and cleaved caspase-3 in the liver and kidney. The results showed that Uro A treatment obviously attenuated d-gal-induced liver and kidney damage. The beneficial effects of Uro A were accompanied by a decline in malondialdehyde (MDA) levels and a rise in the superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and total antioxidant capacity (T-AOC) activity in the liver and kidney and downregulation of the levels of inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6), in serum. Moreover, Uro A could modulate the expression of Bax, Bcl-2 and cleaved caspase-3 in the livers and kidneys of aging mice. These findings suggested that Uro A ameliorated d-gal-induced liver and kidney injury through attenuating oxidative stress, inflammatory responses and apoptosis.

Competing Interests: There are no conflicts to declare.

(This journal is © The Royal Society of Chemistry.)