Loganin Attenuates the Severity of Acute Kidney Injury Induced by Cisplatin through the Inhibition of ERK Activation in Mice

Abstract

Cisplatin is the most widely used chemotherapeutic agent. However, it often causes nephrotoxicity, which results in acute kidney injury (AKI). Therefore, we urgently need a drug that can reduce the nephrotoxicity induced by cisplatin. Loganin is a major iridoid glycoside isolated from Corni fructus that has been used as an anti-inflammatory agent in various pathological models. However, the renal protective activity of loganin remains unclear. In this study, to examine the protective effect of loganin on cisplatin-induced AKI, male C57BL/6 mice were orally administered with loganin (1, 10, and 20 mg/kg) 1 h before intraperitoneal injection of cisplatin (10 mg/kg) and sacrificed at three days after the injection. The administration of loganin inhibited the elevation of blood urea nitrogen (BUN) and creatinine (CREA) in serum, which are used as biomarkers of AKI. Moreover, histological kidney injury, proximal tubule damages, and renal cell death, such as apoptosis and ferroptosis, were reduced by loganin treatment. Also, pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, reduced by loganin treatment. Furthermore, loganin deactivated the extracellular signal-regulated kinases (ERK) 1 and 2 during AKI. Taken together, our results suggest that loganin may attenuate cisplatin-induced AKI through the inhibition of ERK1/2.

Polydatin Attenuates Cisplatin-Induced Acute Kidney Injury by Inhibiting Ferroptosis

“…As early as 30 years ago, researchers proposed that cisplatininduced free iron overload leads to lipid peroxidation in kidneys, but the link between ferroptosis and Cis-AKI has only recently been recognized. Denget al [5] confirmed that cisplatin induced free iron release, GSH depletion, a decrease in GPx4 activity and excessive lipid peroxidation in vivo and in vitro, which was subsequently verified by other groups of investigators [2][3][4]. Ferroptosis, officially named in 2012, is characterized by intracellular iron accumulation and lipid peroxidation apart from classical apoptosis, necrosis, and autophagy [44].…”

“…Several studies have shown that DNA damage, oxidative stress, inflammation, vascular dysfunction, and mitochondrial damage may be involved in the pathogenesis of Cis-AKI [1]. Recently, several studies [2][3][4][5][6] have suggested that cisplatin treatment leads to excessive lipid peroxidation, ferritinophagy-mediated free iron release, and a decrease in the activity of glutathione peroxidase-4 (GPx4), indicating the close link between ferroptosis and Cis-AKI. Hence, ferroptosis intervention may be an effective strategy to attenuate Cis-AKI; nevertheless, there have not been specific drugs against ferroptosis in clinical application to date.…”

C-phycocyanin alleviated cisplatin-induced oxidative stress and inflammation via gut microbiota—metabolites axis in mice

“…In our results, the GSH-based antioxidant system of the liver was comprehensively elevated after the intervention of C-phycocyanin. Cisplatin treatment (10 mg/mL same dose as us) has been found to cause Ferroptosis ( 32 ), and cisplatin-induced depletion of GSH and inactivation of GSH-Px play a central role in the mechanism of Ferroptosis ( 33 ). This means that different from the antioxidant effect on kidney, the antioxidant effect of C-phycocyanin on liver might be resisting Ferroptosis by the GSH pathway.…”

Ojeoksan Ameliorates Cisplatin-Induced Acute Kidney Injury in Mice by Downregulating MAPK and NF-κB Pathways

“…Renal inflammation also plays an important role in cisplatin-induced AKI progression [ 36 , 37 , 38 ]. Thus, the levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) are elevated in cisplatin-induced AKI [ 39 , 40 , 41 ]. The elevation of pro-inflammatory cytokine levels is mediated by the activation of signaling cascade, MAPKs and NF-κB, which are associated with various cell functions, including proliferation, division, stress response, inflammation, and apoptosis [ 42 , 43 ].…”