The response sensitivity to toxic substances is the most concerned performance of animal model in chemical risk assessment. Casper (mitfa w2/w2 ;mpv17 a9/a9 ) , a transparent zebrafish mutant, is a useful in vivo model for toxicological assessment. However, the ability of casper to respond to the toxicity of exogenous chemicals is unknown. In this study, zebrafish embryos were exposed to five environmental chemicals, chlorpyrifos, lindane, α-endosulfan, bisphenol A, tetrabromobisphenol A (TBBPA), and an antiepileptic drug valproic acid. The half-lethal concentration (LC 50 ) values of these chemicals in casper embryos were 62–87 % of that in the wild-type. After TBBPA exposure, the occurrence of developmental defects in the posterior blood island of casper embryos was increased by 67–77 % in relative to the wild-type, and the half-maximal effective concentration (EC 50 ) in casper was 73 % of that in the wild-type. Moreover, the casper genetic background significantly increased the hyperlocomotion caused by chlorpyrifos and lindane exposure compared with the wild-type. These results demonstrated that casper had greater susceptibility to toxicity than wild-type zebrafish in acute toxicity, developmental toxicity and neurobehavioral toxicity assessments. Our data will inform future toxicological studies in casper and accelerate the development of efficient approaches and strategies for toxicity assessment via the use of casper .
Cyclophosphamide (CY), targeting to fast dividing cells, results in bone marrow (BM) suppression, which is the most common side effect of cancer chemotherapy . Interleukin-1 receptor antagonist (IL-1Ra), activated by variety of chemotherapeutic drugs, is a natural inhibitor of interleukin-1 (IL-1) and blocks the functional IL-1 receptor signaling. Our previous studies showed the protective effect of recombinant murine IL-1Ra on hematopoiesis in mice after treatment with chemotherapeutic agent 5-fluorouracil. In this report, we demonstrate that the pretreatment use of recombinant human IL-1Ra (rhIL-1Ra) significantly alleviated chemotherapy-induced peripheral blood injury in mice, and reduced the incidence and severity of neutropenia in beagle dogs. Moreover, acute lethal toxicity in single and repeated CY treatment was markedly reduced by rhIL-1Ra administration. The chemoprotective role of rhIL-1Ra is attributed to the attenuated BM damage, accelerated recovery of BM cells , and enhanced survival of hematopoietic progenitor cells which expressed high level of aldehyde dehydrogenase and IL-1 receptor type I. Thus, our data strongly suggest that the prophylactic use of exogenous rhIL-1Ra renders BM primitive hematopoietic cells resistant to chemotherapy, which provides novel strategies to prevent BM suppression in clinical settings.
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