Dexrazoxane shows cytoprotective effects in zoledronic acid-treated human cells in vitro and in the rabbit tibia model in vivo

Draenert, G.F.; Huetzen, D.O.; Kämmerer, Peer W.; Palarie, Victor; Nacu, Viorel; Wagner, Wilfried

doi:10.1016/j.jcms.2012.01.028

Cited by 15 publications

(16 citation statements)

References 54 publications

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“…This dose dependent cytotoxicity of cisplatin in Saos‐2 cells was described earlier by Incesuz . The negative impact of zolendronic acid on both cell lines, as observed for every concentration in this study, has been described previously for human osteoblasts and for Saos‐2 cells as well .…”

Section: Discussionsupporting

confidence: 87%

The enhancing effect of a laser photochemotherapy with cisplatin or zolendronic acid in primary human osteoblasts and osteosarcoma cells in vitro

Heymann

Ziebart

Kämmerer

et al. 2016

J Oral Pathology Medicine

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Section: Discussionsupporting

confidence: 87%

The enhancing effect of a laser photochemotherapy with cisplatin or zolendronic acid in primary human osteoblasts and osteosarcoma cells in vitro

Heymann

Ziebart

Kämmerer

et al. 2016

J Oral Pathology Medicine

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“…Several local treatment options have been described starting with local application of antibiotics, surgical debridement or hyperbaric oxygen (HBO) therapy, and using growth and differentiation factors [31]. However, recently, using cytoprotectant agents as GGOH is a new and promising approach in MRONJ management [32].…”

Section: Discussionmentioning

confidence: 99%

Geranylgeraniol (GGOH) as a Mevalonate Pathway Activator in the Rescue of Bone Cells Treated with Zoledronic Acid: An In Vitro Study

Fliefel

Entekhabi

Ehrenfeld

et al. 2019

Stem Cells International

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Bisphosphonates (BPs) are the keystone to treat bone disorders. Despite the great benefits of BPs, medication-related osteonecrosis of the jaw (MRONJ) arouse as a potential side effect. Nitrogen-containing BPs (N-BPs) as zoledronate (ZA) act by the inhibition of specific enzymes of the mevalonate pathway resulting in altering protein prenylation which is required for the posttranslational maturation of the small GTP-binding proteins. Geranylgeraniol (GGOH) is an intermediate product in the mevalonate pathway having positive effects on different cell types treated with BPs by salvaging protein prenylation improving cell viability and proliferation in tissue regeneration, thus overcoming N-BP-induced apoptosis. Here, the effect of different concentrations of zoledronate (ZA) on the bone cells has been investigated by cell viability assay, live/dead staining, and western blot to understand if GGOH was able to rescue bone cells and levels of statistical significance were indicated at ∗P < 0.05, ∗∗P < 0.01, ∗∗∗P < 0.001, and ∗∗∗∗P < 0.0001. Although the high concentration of ZA had significantly decreased the cell viability in the bone cells, GGOH reversed the action of ZA on the cells while at very high concentration; it caused severe reduction in the cell viability. Rap1A, a member of the GTPases family, was expressed in the negative controls but was absent in cells treated with high concentrations of ZA. The addition of GGOH had increased the expression of Rap1A up to a certain limit. The experiments proved that ZA acts directly on the mevalonate pathway and protein prenylation and that GGOH could be applied as a future local therapy to MRONJ.

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“…The decrease in expression of all these factors can favor the occurrence of the side effects of N‐BPs. Interestingly, the cytoprotectant dexrazoxane was shown to protect osteoblasts from N‐BPs in vitro and in vivo (Draenert et al, ) and could have a place in the arsenal for limiting N‐BP side effects.…”

Section: Future Directions For Controlling the Side Effects Of N‐bpsmentioning

confidence: 99%

Paradoxical side effects of bisphosphonates on the skeleton: What do we know and what can we do?

Vargas-Franco

Castañeda

Rédini

et al. 2018

Journal Cellular Physiology

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Bisphosphonates are considered the most effective drugs for controlling adult and pediatric osteolytic diseases. Although they have been used successfully for many years, several side effects, such as osteonecrosis of the jaw, delayed dental eruption, atypical femoral fracture, and alterations to the bone growth system, have been described. After an overview of nitrogenous bisphosphonate, the purpose of this article is to describe their mechanisms of action and current applications, review the preclinical and clinical evidence of their side effects in the skeleton ("what we know"), and describe current recommendations for preventing and managing these effects ("what we can do"). Finally, promising future directions on how to limit the occurrence of these side effects will be presented.

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Dexrazoxane shows cytoprotective effects in zoledronic acid-treated human cells in vitro and in the rabbit tibia model in vivo

Cited by 15 publications

References 54 publications

The enhancing effect of a laser photochemotherapy with cisplatin or zolendronic acid in primary human osteoblasts and osteosarcoma cells in vitro

The enhancing effect of a laser photochemotherapy with cisplatin or zolendronic acid in primary human osteoblasts and osteosarcoma cells in vitro

Geranylgeraniol (GGOH) as a Mevalonate Pathway Activator in the Rescue of Bone Cells Treated with Zoledronic Acid: An In Vitro Study

Paradoxical side effects of bisphosphonates on the skeleton: What do we know and what can we do?

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