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Free Radic Res. 2017 Jul-Aug;51(7-8):669-683. doi: 10.1080/10715762.2017.1361532. Epub 2017 Aug 11.

Renoprotective mechanisms of Astragaloside IV in cisplatin-induced acute kidney injury.

Author information

1
a Department of Nephrology, Molecular Cell Laboratory for Kidney Disease , Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai , China.
2
b Transplantation Center of Ren Ji Hospital, School of Medicine , Shanghai Jiao Tong University , Shanghai , China.

Abstract

Nephrotoxicity remains a serious adverse effect of cisplatin chemotherapy, limiting its clinical usage. Numerous studies show that oxidative stress and inflammation are closely associated with cisplatin-induced renal damage. Astragaloside IV (AS-IV) has been found to possess antioxidant and anti-inflammation functions. Therefore, we investigated the potential curative effects of AS-IV against cisplatin-induced renal injury and the possible cellular mechanism for activity, both in vitro and in vivo. We found that pretreatment of HK-2 cells with AS-IV could mitigate cisplatin-induced cell damage caused by oxygen-free radicals and the inflammatory response, as evidenced by reduced formation of reactive oxygen species (ROS) and inflammatory cytokines. AS-IV improved cisplatin-induced renal dysfunction and histopathological injury in mice. Additionally, AS-IV enhanced the activities of total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), and catalase (CAT). It also inhibited cisplatin-induced overproduction of kidney injury molecule-1 (KIM-1), malondialdehyde (MDA), tumour necrosis factor-α (TNF - α), and interleukin-1β (IL-1β) in kidney tissues. We found that the protective effects of AS-IV occurred via activation of the nuclear factor-erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) proteins and inhibition of nuclear factor-κappaB (NF-κB) activation. Further, small interfering RNA (siRNA) knockdown of Nrf2 abrogated the protective effects of AS-IV against cisplatin-induced oxidative stress and blocked the inhibitory effects of AS-IV on cisplatin-induced NF-κB activation and inflammatory cytokine production. In conclusion, our data suggested that AS-IV attenuated cisplatin-mediated renal injury, and these protective effects might be due to inhibition of both oxidative damage and inflammatory response via activation of Nrf2 system and suppression of NF-κB activation.

KEYWORDS:

Astragaloside IV; KIM-1; Nrf2; acute kidney injury (AKI); cisplatin

PMID:
28750561
DOI:
10.1080/10715762.2017.1361532
[Indexed for MEDLINE]

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