Key result
Pretreatment with dabigatran significantly improved kidney function and decreased oxidative stress and apoptotic markers in an animal model of cisplatin-induced nephrotoxicity.
Why the study?
Cisplatin nephrotoxicity is a major complication limiting its cancer use, and this study investigated the role of thrombin and the preventive effect of dabigatran.
Does dabigatran prevent cisplatin-mediated nephrotoxicity in an animal model?
Does dabigatran prevent cisplatin-mediated nephrotoxicity in an animal model?
Dabigatran mitigates cisplatin-induced nephrotoxicity in an animal model by downregulating the thrombin pathway and reducing oxidative stress and apoptosis.
Supports exploration of dabigatran for cisplatin nephrotoxicity; leaves open clinical translation pending human studies.
INTRODUCTION: Cisplatin (CDDP) nephrotoxicity is one of the most significant complications limiting its use in cancer therapy. OBJECTIVES: This study investigated the pivotal role played by thrombin in CDDP-mediated nephrotoxicity. This work also aimed to clarify the possible preventive effect of Dabigatran (Dab), a direct thrombin inhibitor, on CDDP nephrotoxicity. METHODS: Animals were grouped as follow; normal control group, CDDP nephrotoxicity group, CDDP + Dab 15, and CDDP + Dab 25 groups. Four days following CDDP administration, blood and urine samples were collected to evaluate renal function. Moreover, tissue samples were collected from the kidney to determine apoptosis markers, oxidative stress and histopathological evaluation. An immunofluorescence analysis of tissue factor (TF), thrombin, protease-activated receptor-2 (PAR2), fibrin, pERK1/2 and P53 proteins expression was also performed. RESULTS: Thrombin, pERK, cleaved caspase-3, and oxidative stress markers were significantly elevated in CDDP-treated group. However, pretreatment of animals with either low or high doses of Dab significantly improved kidney function and decreased oxidative stress and apoptotic markers. CONCLUSION: We conclude that thrombin is an important factor in the pathogenesis of CDDP kidney toxicity via activation of ERK1/2, P53 and caspase-3 pathway, which can be effectively blocked by Dab.
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Ewees et al. (2021) studied Cisplatin-mediated nephrotoxicity. Dabigatran vs. Cisplatin alone (CDDP nephrotoxicity group) was evaluated on Kidney function, oxidative stress, and apoptotic markers. Pretreatment with dabigatran significantly improved kidney function and decreased oxidative stress and apoptotic markers in an animal model of cisplatin-induced nephrotoxicity.
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