Baicalein and Αlpha-Tocopherol Inhibit Toll-like Receptor Pathways in Cisplatin-Induced Nephrotoxicity

Abstract

Cisplatin (CP) is a conventional chemotherapeutic agent with serious adverse effects. Its toxicity was linked to the stimulation of oxidative stress and inflammation. As a result, this study explored the protective effect of baicalein and alpha-tocopherol in nephrotoxicity induced by cisplatin. Until receiving an intraperitoneal injection of CP (3 mg/kg BW), rats were given baicalein orally 100 mg/kg for seven days or/and a single intraperitoneal injection of α-tocopherol 250 mg/kg. Renal function was tested to explore whether baicalein and α-tocopherol have any beneficial effects; blood urea nitrogen (BUN), serum creatinine, malondialdehyde (MDA) content, antioxidant activity biomarkers and histopathology of renal tissue, oxidative stress biomarkers, inflammatory response markers, and histopathological features of kidney architecture were measured. Cisplatin treatment resulted in extreme renal failure, as measured by high serum creatinine and BUN levels and severe renal changes. Cisplatin therapy resulted in increased lipid peroxidation and decreased glutathione and superoxide dismutase levels, reflecting oxidative stress. Upon treatment with α-tocopherol, baicalein, and combined therapy, there was augmentation in the antioxidant status as well as a reduction in IL-6, NF-κB, TNF, TLR2, and TLR4 and a significant increase in Keap-1 and NRF-2. The combined treatment was the most effective and the nearest to the normal status. These findings suggest that baicalein and α-tocopherol may be useful in preventing cisplatin-induced nephrotoxicity.

Pro-Inflammatory Signalling PRRopels Cisplatin-Induced Toxicity

“…Some studies have shown that depletion of TLR2 is associated with protection and subsequent reductions in pro-inflammatory IL-17A in CIN, and especially when there is simultaneous inhibition of TLR4 expression or activity. However, there are also studies that connote to the opposite [92,93]. Reports on its role in CITs are limited though and it poses an intriguing area for further investigation, particularly since it is not clear which heterodimer is more involved in this process-TLR2/TLR1 or TLR2/TLR6.…”

Regulation of Cell Signaling Pathways and Non-Coding RNAs by Baicalein in Different Cancers

“…Baicalein has a molecular weight of 270.24 g/mol. Baicalein has been shown to improve disease severity by regulation of different disease-related proteins [ 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ]. Therefore, before a comprehensive and mechanistic analysis of baicalein-mediated cancer chemopreventive properties, we present an overview of antibacterial, antiviral, and oxidative-stress-modulating activities of baicalein.…”

Based on network pharmacology and molecular docking to explore the protective effect of Epimedii Folium extract on cisplatin-induced intestinal injury in mice

“…Oxidative stress plays an essential role in the pathogenesis of cisplatin-induced cytotoxicity, which indicates that the application of antioxidants can effectively ameliorate cisplatin-induced toxicity ( Mansour et al, 2006 ). For this purpose, past studies have demonstrated that various active extracts or active components obtained from herbal medicines have a significant activity in antagonizing the side effects caused by cisplatin ( Awadalla et al, 2022 ; Gholampour et al, 2022 ; Pei et al, 2022 ). According to literature reports, flavonoids extracted from Epimedii Folium can effectively resist the toxicity caused by cisplatin ( Ma et al, 2015 ).…”