Qilong capsule alleviates ponatinib-induced ischemic stroke in a zebrafish model by regulating coagulation, inflammation, and apoptosis

Abstract

Background: Qilong capsule (QLC) is a traditional Chinese medicine commonly used to treat ischemic stroke (IS). But the pharmacodynamic mechanism of QLC is not clear. Method: we used an existing zebrafish model to explore the protective mechanism of QLC on IS. We treated normally-developing zebrafish larvae with QLC and ponatinib 2 days post fertilization, and used the area of cerebral vascular thrombosis, red blood cell staining intensity, and brain cell apoptosis to quantitate QLC efficacy against IS. Real-time quantitative polymerase chain reaction (qPCR) was used to detect changes in the expression of genes involved in coagulation, inflammation, vascular endothelium, and apoptosis. Result: We found that QLC reduced the area affected by ponatinib-induced cerebral vascular embolism, erythrocyte staining intensity, and the number of apoptotic brain cells. qPCR showed that QLC inhibited the expression of genes related to coagulation, inflammation, and apoptosis. Conclusion: QLC had a significant protective efficacy in ponatinib-induced IS.

Endothelial function in patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors is not related to cardiovascular risk assessed by SCORE2 algorithm

“…Our results seem to indicate that in CML patients in our study eligible for SCORE2 and SCORE2-OP analysis, endothelial dysfunction was determined mainly by CML-specific factors not by classical risk factors of cardiovascular diseases. Given the emerging evidence from preclinical studies on the detrimental effects of TKIs on endothelial function [18][19][20][21][22][23], we tested whether endothelial function in CML patients might have been influenced by TKI treatment. The number of parameters of endothelial function measured using the FMD, RH-PAT, and FMSF methods correlated negatively with patients' age.…”

“…In several other studies, ponatinib-and other TKI-related effects, including demonstration of detrimental effects on cell permeability, migration, wound closure, tube formation, and cell viability on the endothelium, were reported [19]. Finally, although ponatinib inhibited platelet activation and aggregate formation under shear stress [20], this TKI induced prothrombotic angiopathy in mice [21] and stroke in zebrafish model [22]. Taken together, it appears that ponatinib and other TKIs induce arterial thrombosis through endothelial dysfunction [23].…”