Embelin attenuates cisplatin‐induced nephrotoxicity: Involving inhibition of oxidative stress and inflammation in addition with activation of Nrf‐2/Ho‐1 pathway

Abstract

In kidneys, elevated levels of inflammatory cytokines and oxidative stress were observed in nephrotoxicity triggered by cisplatin. Embelin has the anti-inflammatory property. It also got anti-tumorigenic and antioxidant properties. In this research, we analyzed the actions of embelin on nephrotoxicity triggered by cisplatin and vital actions by which it increases antioxidant actions and corrects the inflammation after embelin administration during nephrotoxicity triggered by cisplatin. Kidney function markers including blood urea nitrogen; serum creatinine; the markers of oxidative stress like malondialdehyde (MDA), antioxidant systems like glutathione, superoxide dismutase, glutathione S-transferase, catalase, and glutathione reductase; inflammation markers like nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF-α), and interleukin-1 beta (IL-1β); and the extent of nuclear factor-erythroid-2 p45-related factor-2 (Nrf2) and heme oxygenase-1 (HO-1) were determined. Histopathology studies of kidneys were also used to analyze nephrotoxicity induced by cisplatin. Treatment with embelin (25 and 50 mg/kg) upgrades the function of kidneys, by elevating antioxidant levels and reducing the MDA level in cisplatin-administered rats. Embelin treatment demonstrated a significant curtailment of oxidative stress as well as increased the activities of antioxidant enzymes, endogenously. Cisplatin upregulates cytokines (i.e., TNF-α and IL-1β) and NF-κB, and downregulates Nrf2 and HO-1. Embelin treatment also reduced the infiltration of neutrophils in the renal tubules and thus reduced the level of histological impairment. The outcome of this study implements that the signaling pathway of Nrf2/HO-1 may be the principal mechanism of embelin for protection from nephrotoxicity triggered by cisplatin, and thus, embelin diminishes oxidative stress and inflammation by impeding NF-κB.

N6-2-hydroxyethyl-adenosine ameliorate cisplatin induced acute kidney injury in mice

“…Numerous studies have linked cisplatin-induced toxicity to a decrease in glomerular filtration rate and subsequently increased serum BUN and creatinine levels (Malik et al 2016;Boroja et al 2018). Our findings are consistent with previous studies showing CP-induced significant elevation of serum creatinine and BUN levels (Qin et al 2019;Sioud et al 2020). Our study also revealed an increase in serum BUN and creatinine levels in the CP model group suggesting kidney damage and HEA effectively attenuated cisplatin-induced kidney damages by reducing serum BUN and creatinine levels.…”

“…SOD, CAT and GSH-Px antioxidant enzymes offers protection against oxidative insults in the cells and the reduction in their activities makes the target cells and organs vulnerable to oxidative damages (Hassan et al 2017;Meng et al 2017). Our results indicated that cisplatin impaired the activities of SOD, CAT and GSH-Px and increased the content of MDA in the kidney which was consistent with results from other studies (Adeoye et al 2019;Kandemir et al 2019;Qin et al 2019). Treatment with HEA improved the activities of CAT, SOD and GSH-Px in the kidney.…”

Nephroprotective activity of natural products against chemical toxicants: The role of Nrf2/ARE signaling pathway

“…Nrf2 stimulated the synthesis of a series of antioxidant proteins such as HO‐1, GSH, GR, GST, CAT, and SOD and by affecting these inflammatory pathways, regulating the production of inflammatory mediators such as NF‐κB, TNF‐α, and IL‐1β. These changes have been shown to reduce the level of tissue damage markers and to improve kidney function tests such as creatinine clearance and blood nitrogen levels (Qin et al., 2019).…”

Sodium tanshinone IIA sulfonate attenuates tumor oxidative stress and enhances apoptosis in an intermittent hypoxia mouse model

“…As a transcription factor, Nrf2 is downregulated under oxidative stress environment. Numerous antioxidant therapies have the function to activate Nrf2-related signaling pathways [38][39][40]. Evidence has shown the lower expression of Nrf2 in OSA patients or the IH animal models [41,42].…”