Treatment with catalpol protects against cisplatin‑induced renal injury through Nrf2 and NF‑κB signaling pathways

Abstract

Cisplatin (CP) is one of the most widely used chemotherapy drugs for cancer treatment, but it often leads to nephrotoxicity. It is well known that catalpol exhibits antioxidant and anti-inflammatory functions, thus the present study aimed to investigate the potential protective effects of catalpol on CP-induced kidney injury in rats, in addition to determining the underlying mechanisms. Sprague-Dawley rats were treated with 25, 50 or 100 mg/kg catalpol for two days, injected with 20 mg/kg cisplatin and catalpol on day 3 and sacrificed on day 4. The histological analysis of isolated kidney tissues was performed using hematoxylin and eosin staining, cleaved caspase-3 expression levels were analyzed using western blotting and the expression levels of inflammatory cytokines in the tissues, including tumor necrosis factor α (TNF-α), interleukin (IL)-1β, IL-6, IL-8, IL-10 and inducible nitric oxide synthase (iNOS) were evaluated using ELISAs. Furthermore, the mRNA and protein expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), kelch-like ECH-associated protein 1 (Keap1), NF-κB and inhibitory κB (IκB) were determined using reverse transcription-quantitative PCR and western blotting, respectively. The results revealed that the treatment with catalpol prevented the histopathological injury and renal dysfunction caused by CP. In addition, catalpol significantly suppressed the CP-induced apoptosis of tubular cells, inhibited the CP-induced upregulation of TNF-α, IL-1β, IL-6, IL-8 and iNOS and promoted the production of the anti-inflammatory cytokine IL-10. Additionally, the mRNA and protein expression levels of Nrf2, HO-1 and IκB in the kidney tissues were increased, whereas the expression levels of Keap1 and NF-κB were significantly decreased following the treatment with catalpol. In conclusion, these results suggested that catalpol may inhibit CP-induced renal injury and suppress the associated inflammatory response through activating the Nrf2 and inhibiting the NF-κB signaling pathways, respectively.

Catalpol Alleviates Ang II-Induced Renal Injury Through NF‐κB Pathway and TGF-β1/Smads Pathway

“…A recent study about cisplatin-induced renal injury shows that catalpol inhibits cisplatin-induced upregulation of pro-inflammatory cytokine through activating the Nrf2 and inhibiting the NF-kB signaling pathways. 32 As expected, in our study, we found that catalpol significantly decreased proinflammatory cytokine and the expression of p-IKBa and p-65. Taken together, catalpol reduced Ang II-induced renal inflammation through NF-kB signaling pathway.…”

Catalpol ameliorates inflammation and oxidative stress via regulating Sirt1 and activating Nrf2/HO‐1 signaling against acute kidney injury

“…Liu et al demonstrated that Cat treatment ameliorated psoriatic‐like symptoms through upregulating Sirt1 via blocking NF‐κB, and MAPKs signaling 57 . A former research has implied that Cat may inhibit cisplatin‐induced renal injury and suppress the associated inflammatory response through activating the Nrf2/HO‐1 signaling 58 . Thus, it was assumed that Cat might exert renoprotective effects in SAKI via upregulating Sirt1 and activating Nrf2/HO‐1 signaling.…”

“…57 A former research has implied that Cat may inhibit cisplatininduced renal injury and suppress the associated inflammatory response through activating the Nrf2/HO-1 signaling. 58…”

Anti‐inflammatory effect and mechanism of catalpol in various inflammatory diseases

“…In vivo KI mice Inhibiting NF-κB pathway (Zhang et al [2020]) LPS-induced neurotoxicity (Jiang et al, 2008;Tian et al, 2006), suggesting that catalpol exerts a protective effect on dopaminergic neurons by inhibiting microglia activation and reducing the production of proinflammatory factors. Bi et al pretreated astrocytes with 0.1 mM and 0.5 mM catalpol for 1 h and significantly inhibited NO, ROS, iNOS production, and NF-κB activation in a dose-dependent manner.…”

“…Studies have shown that ischemia-reperfusion (IRI)(Gill et al, 2005), angiotensin II (Ang II)(Ruiz-Ortega et al, 2002), and the chemotherapeutic agent cisplatin (CP)(Holditch et al, 2019) can cause AKI. Zhu et al found that catalpol significantly reduced the activity of TNF-α, IL-1β, IL-6, and IL-10 in kidney IRI mice(Zhu et al, 2015).Zhang et al found that catalpol reduced the inflammatory response to kidney injury induced by Ang II and CP by inhibiting the NF-κB signaling pathway(Cong et al, 2022;Zhang et al, 2020). In summary, catalpol attenuates the inflammatory response in kidney injury by inhibiting the NF-κB signaling pathway.3.4.2 | Chronic kidney diseaseThe development of chronic kidney disease is associated with mechanisms such as inflammation and oxidative stress.…”