Abstract
Aging is an independent risk factor for the development of age-related progressive kidney injury. As a part of the aging process, kidney aging has been indicated to be associated with oxidative stress-induced damage. Ameliorating oxidative damage is therefore considered a promising strategy for delaying kidney aging. Alginate oligosaccharide (AOS) has been reported to have a wide range of biological and pharmacological activities. However, no studies have focused on the role of AOS in delaying the kidney aging process. In this study, we aimed to evaluate the potential effects of AOS on kidney aging and its possible mechanisms. Subcutaneous injection of D-galactose (D-gal) (200 mg·kg−1·d−1) in C57BL/6J mice for 8 weeks was used to establish the aging model. AOS (200 mg·kg−1·d−1) was administered via oral gavage for the last four weeks. As a result, AOS inhibited the D-gal-induced upregulation of aging markers and significantly improved the kidney index and kidney function of D-gal-induced mice. In addition, AOS ameliorated the degree of tissue damage and fibrosis in the aging kidney. To further explore the potential mechanisms by which AOS attenuates the kidney aging process, the associated oxidative stress-induced damage was analyzed in depth. The data showed that AOS upregulated the expression of Klotho and decreased malondialdehyde levels by increasing the expression of antioxidant enzymes. Furthermore, our results suggested that AOS activated the nuclear factor erythrogen-2 associated factor 2 (Nrf2) pathway by promoting Nrf2 nuclear translocation in aging mice and upregulated the downstream expression of heme oxygenase-1 (HO-1) and NADPH quinone oxidoreductase 1 (NQO1). In conclusion, the present study demonstrated that AOS is a promising agent for attenuating kidney aging, and the underlying molecular mechanisms are related to the activation of the Nrf2 signaling pathway.
Highlights
Aging is an extremely complex and unstoppable natural process [1]
According to the free radical aging theory that was first proposed by Hamann, oxidative stress damage caused by reactive oxygen species (ROS) and free radicals plays an important role in the aging process [3]
Alginate oligosaccharide (AOS) treatment had no significant effects on the expression of nuclear factor erythrogen-2 associated factor 2 (Nrf2) in the cytosolic fraction. These findings indicate that Nrf2 is associated with D-gal-induced kidney aging, and the protective effects of AOS on D-gal-induced aging kidney are related to promoting the translocation of Nrf2 protein from the cytoplasm to the nucleus
Summary
As a part of the aging process, kidney aging leads to the inevitable loss of kidney function [2]. According to the free radical aging theory that was first proposed by Hamann, oxidative stress damage caused by reactive oxygen species (ROS) and free radicals plays an important role in the aging process [3]. A noteworthy question is whether oxidative stress is involved in the normal process of kidney aging. Studies have shown that oxidative stress damage is a major contributor to the kidney aging process [4]. Excessive ROS in the aging kidney directly results in oxidative stress, which leads to an imbalance in oxidation-reduction reactions (REDOX), further contributing to the acceleration of kidney aging [5]. Resistance to oxidative stress may be a promising therapeutic strategy for delaying the kidney aging process [7]
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