Cisplatin exposure impairs ionocytes and hair cells in the skin of zebrafish embryos

Hung, Giun Yi; Wu, Ciao Ling; Chou, Yi Ling; Chien, Chiang Ting; Horng, Jiun Lin; Li, Lin

doi:10.1016/j.aquatox.2019.02.006

Cited by 29 publications

(13 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, further long-term investigation is required to confirm adverse effect on bone biomarkers. Moreover, we addressed potential toxicity of Pt released from Pt-BP compounds in a zebrafish model, since this model provides a 500-fold higher sensitivity for early assessment of toxic effects caused by Pt-based chemotherapeutics 48,49 . As such, the zebrafish model is a highly valuable model for initial ototoxicity screening.…”

Section: Discussionmentioning

confidence: 99%

Targeting of radioactive platinum-bisphosphonate anticancer drugs to bone of high metabolic activity

Nadar

Farbod

Schilden

et al. 2020

Sci Rep

View full text Add to dashboard Cite

platinum-based chemotherapeutics exhibit excellent antitumor properties. However, these drugs cause severe side effects including toxicity, drug resistance, and lack of tumor selectivity. Tumor-targeted drug delivery has demonstrated great potential to overcome these drawbacks. Herein, we aimed to design radioactive bisphosphonate-functionalized platinum (195m Pt-BP) complexes to confirm preferential accumulation of these pt-based drugs in metabolically active bone. In vitro nMR studies revealed that release of pt from pt Bp complexes increased with decreasing pH. Upon systemic administration to mice, Pt-BP exhibited a 4.5-fold higher affinity to bone compared to platinum complexes lacking the bone-seeking bisphosphonate moiety. these pt-Bp complexes formed less pt-DnA adducts compared to bisphosphonate-free platinum complexes, indicating that in vivo release of pt from pt-Bp complexes proceeded relatively slow. Subsequently, radioactive 195m pt-Bp complexes were synthesized using 195m pt(no 3) 2 (en) as precursor and injected intravenously into mice. Specific accumulation of 195m pt-Bp was observed at skeletal sites with high metabolic activity using micro-Spect/ct imaging. Furthermore, laser ablation-ICP-MS imaging of proximal tibia sections confirmed that 195m pt Bp colocalized with calcium in the trabeculae of mice tibia. Most types of tumors, i.e. breast, prostate, lung, kidney, and thyroid, metastasize to bone since its physiological environment facilitates the formation and growth of cancer cells 1,2. These metastases affect healthy bone, which then become the primary cause of mortality 3. Distant metastases are the leading cause of death for both breast and prostate cancer patients, with 65-75% and 90% of these patients developing bone metastases in advanced stages, respectively 4,5. Bone metastases are often associated with accelerated bone resorption leading to complications such as skeletal-related events (SREs), bone pain or hypercalcemia 6,7. Unfortunately, current treatments for bone metastases are limited. Bisphosphonates (BP) and denosumab are most commonly used for palliative treatment to prevent or limit SREs 8. Although such treatments inhibit osteoclast activity and prevent the progression of metastases, they do not kill cancer cells effectively and do not improve the quality of life of patients substantially 9. Consequently, the development of effective therapies to treat bone metastases remains a major clinical challenge.

show abstract

Section: Discussionmentioning

confidence: 99%

Targeting of radioactive platinum-bisphosphonate anticancer drugs to bone of high metabolic activity

Nadar

Farbod

Schilden

et al. 2020

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Zebrafish are a well-established vertebrate system for toxicological studies and preclinical drug assessment. , The rapid cell division of early embryos is an effective experimental model to evaluate chemotherapies and other compounds in the context of nontransformed cells in vivo. − Cisplatin has been shown to effectively kill the hair cells of zebrafish lateral line, − zebrafish have been used to examine cisplatin, and other metal-based chemotherapies cause cell death …”

Section: Discussionmentioning

confidence: 99%

Supercritical CO₂ Processing Generates Aqueous Cisplatin Solutions with Enhanced Cancer Specificity

et al. 2020

View full text Add to dashboard Cite

Cisplatin is a highly toxic material used clinically as a potent chemotherapeutic. While effective against some cancers, toxicity limits widespread use and low solubility confounds delivery. To formulate a better tolerated and more water-soluble form of cisplatin, we designed a rapid expansion of supercritical solutions (RESS) technique with supercritical carbon dioxide (sc-CO2) to collect nanoclusters of cisplatin embedded in dry ice, in a dual-stage collection vessel cooled to liquid nitrogen temperature. These nanoclusters were solubilized in deionized water and further concentrated (up to 51.3 mM) by a Rotovap process, yielding stable cisplatin solutions with solubility up to 15 × (w/w) greater than that of normal cisplatin. Extensive material characterizations of the solutions were carried out to determine any chemical and/or structural changes of the RESS-processed cisplatin. In vitro cytotoxicity studies of these aqueous solutions showed increased cell viability and early apoptosis compared to equivalent concentrations of standard cisplatin solutions. In vivo studies using zebrafish embryos revealed that standard cisplatin solutions were acutely toxic and caused death of rapidly proliferating cells compared to RESS-processed cisplatin, which were better tolerated with reduced general cell death. Increased water solubility and matched chemical identity of RESS-processed aqueous cisplatin solutions indicate the potential to open up novel drug-delivery routes, which is beneficial for new pharmaceutical design and development.

show abstract

“…By means of "scanning ion-selective electrode technique" (SIET) the in vivo functional alteration of zebrafish hair cells/ionocytes induced by cisplatin was investigated [105]. This method resulted much more sensitive than survival studies in detecting alterations in aquatic animals due to exposure of cisplatin.…”

Section: Ecotoxicological Potencymentioning

confidence: 99%

The Dark Side of Platinum Based Cytostatic Drugs: From Detection to Removal

et al. 2021

View full text Add to dashboard Cite

The uncontrolled release of pharmaceutical drugs into the environment raised serious concerns in the last decades as they can potentially exert adverse effects on living organisms even at the low concentrations at which they are typically found. Among them, platinum based cytostatic drugs (Pt CDs) are among the most used drugs in cancer treatments which are administered via intravenous infusion and released partially intact or as transformation products. In this review, the studies on environmental occurrence, transformation, potential ecotoxicity, and possible treatment for the removal of platinum cytostatic compounds are revised. The analysis of the literature highlighted the generally low total platinum concentration values (from a few tens of ng L−1 to a few hundred μg L−1) found in hospital effluents. Additionally, several studies highlighted how hospitals are sources of a minor fraction of the total Pt CDs found in the environment due to the slow excretion rate which is longer than the usual treatment durations. Only some data about the impact of the exposure to low levels of Pt CDs on the health of flora and fauna are present in literature. In some cases, adverse effects have been shown to occur in living organisms, even at low concentrations. Further ecotoxicity data are needed to support or exclude their chronic effects on the ecosystem. Finally, fundamental understanding is required on the platinum drugs removal by MBR, AOPs, technologies, and adsorption.

show abstract

Cisplatin exposure impairs ionocytes and hair cells in the skin of zebrafish embryos

Cited by 29 publications

References 57 publications

Targeting of radioactive platinum-bisphosphonate anticancer drugs to bone of high metabolic activity

Targeting of radioactive platinum-bisphosphonate anticancer drugs to bone of high metabolic activity

Supercritical CO₂ Processing Generates Aqueous Cisplatin Solutions with Enhanced Cancer Specificity

The Dark Side of Platinum Based Cytostatic Drugs: From Detection to Removal

Contact Info

Product

Resources

About

Cisplatin exposure impairs ionocytes and hair cells in the skin of zebrafish embryos

Cited by 29 publications

References 57 publications

Targeting of radioactive platinum-bisphosphonate anticancer drugs to bone of high metabolic activity

Targeting of radioactive platinum-bisphosphonate anticancer drugs to bone of high metabolic activity

Supercritical CO2 Processing Generates Aqueous Cisplatin Solutions with Enhanced Cancer Specificity

The Dark Side of Platinum Based Cytostatic Drugs: From Detection to Removal

Contact Info

Product

Resources

About

Supercritical CO₂ Processing Generates Aqueous Cisplatin Solutions with Enhanced Cancer Specificity