Biomedicine & pharmacotherapy = Biomédecine & pharmacothérapie
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Biomed. Pharmacother. · Feb 2020
Inhibition of CXCL1-CXCR2 axis ameliorates cisplatin-induced acute kidney injury by mediating inflammatory response.
One of the limiting side effects of cisplatin use in cancer chemotherapy is nephrotoxicity. Inflammation is now believed to play a major role in the pathogenesis of cisplatin-induced acute kidney injury (AKI), and the mediators of inflammation contribute to it. CXCL1 was recently reported to be involved in renal physiology and pathology in ischemia mouse model; however, its roles and mechanisms in cisplatin-induced AKI are completely unknown. ⋯ Furthermore, inhibition of CXCR2 by intragastric administration of repertaxin in mice with AKI reduces kidney injury associated with a reduction of inflammatory cytokines and neutrophils infiltration. Finally, we found that CXCL1/CXCR2 regulated cisplatin-induced inflammatory responses via the P38 and NF-κB signaling pathways in vitro and in vivo. In conclusion, our results indicate that CXCL1-CXCR2 signaling axis plays a crucial role in the pathogenesis of cisplatin-induced AKI through regulation of inflammatory response and maybe a novel therapeutic target for cisplatin-induced AKI.
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Biomed. Pharmacother. · Feb 2020
Jiawei Yanghe decoction ameliorates cartilage degradation in vitro and vivo via Wnt/β-catenin signaling pathway.
Jiawei Yanghe decoction (JWYHD) is a Traditional Chinese Medicine (TCM) formula for the treatment of osteoarthritis (OA), however the underlying mechanisms of action of JWYHD in OA are not fully explored. This study investigates how JWYHD protects cartilage from degradation via Wnt/β-catenin signaling pathway. The chondroprotective and anti-inflammatory effect of JWYHD on chondrocytes in vitro and on MIA-induced OA rat model in vivo were investigated. ⋯ It was also demonstrated that JWYHD decreased serum and synovium pro-inflammatory cytokines, IL-1β, IL-6 and TNF-α in MIA-induced OA rats and ameliorated the cartilage degradation. Histopathological staining, macroscopic observation and micro-CT scan with 3-dimension remodeling showed a cartilage protective effect of JWYHD. In conclusion, JWYHD possess multiple capabilities including preventing chondrocyte apoptosis, preserving integrity of extracellular matrix and anti-inflammatory effect in the treatment of OA both in vitro and in vivo.
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Biomed. Pharmacother. · Feb 2020
Flavonoid fisetin alleviates kidney inflammation and apoptosis via inhibiting Src-mediated NF-κB p65 and MAPK signaling pathways in septic AKI mice.
Sepsis is defined as end-organ dysfunction resulting from the host's inflammatory response to infection. One of the most common sepsis-injured organs is the kidneys, resulting in acute kidney injury (AKI) that contributes to the high morbidity and mortality, especially patients in the intensive care unit. Fisetin, a naturally occurring flavonoid, has been reported to protect against the rat of lipopolysaccharide (LPS)-induced acute lung injury. However, the effect of fisetin on septic AKI remains unknown. ⋯ Fisetin alleviated kidney inflammation and apoptosis to protect against LPS-induced septic AKI mice via inhibiting Src-mediated NF-κB p65 and MAPK signaling pathways.