Toxicities of Therapeutic Agents Used in Medicine
- Rentsendorj and colleagues reported a scientific paper that may have relevant implications for understanding the safety of haemoglobin-based products [1]. They examined in vivo the effects of the polymerized form of haemoglobin (HbG) on transcriptional regulation, activity, and expression of the renal antioxidant enzymes, to investigate its potential ability to promote oxidative tissue injury. Their findings provided evidence that renal exposure as well as central neurons exposure to HbG, (previously demonstrated), suppresses the function of the major antioxidant defence systems.
- Chiorazzi and co-workers reviewed current views in platinum-related drug mechanisms that cause peripheral neurotoxicity. Cisplatin, carboplatin, and oxaliplatin, the three most famous neurotoxic platinum-based chemotherapy agents employed for the treatment of several solid tumours, affected the Dorsal Root Ganglia neuron machinery preferentially damaging mitochondria, membrane potentials, and anti-oxidative protective systems [2].
- Callejo and colleagues examined in depth the state of art of cisplatin-induced ototoxicity. In addition to peripheral neurotoxicity, cisplatin produces a bilateral, progressive, irreversible neurosensory hearing loss due to the production of reactive oxygen species in the inner ear tissue. The authors reviewed the currently available preventive and protective strategies, discussing the problems related to the interfering effects of systemic administration and consequently promoting local injection strategies [3].
- Bernocchi and coworkers studied the effects of cisplatin on the immature brain, which appears to be more vulnerable to injury than the adult brain. Changes in the intracellular calcium homeostasis within the central nervous system architecture after cisplatin exposure demonstrates that the equilibrium and synergy between calcium proteins to limit neuroarchitecture damages [4] is essential.
- Argyriou discussed the important open issue of the availability of reliable biomarkers to allow prompt identification of patients at high risk of developing oxaliplatin-induced peripheral neuropathy. This review described the relationship between some peculiar genetic variants and the pathogenesis, clinical outcome, and management of peripheral neuropathy [5].
- As reported by Nicolini and colleagues, not only the Dorsal Root Ganglia sensory neurons, but also axonal transport can be perturbed by antineoplastic agents. Axonal bidirectional trafficking along peripheral nerves can be impaired by both “old” but widely employed, and by “young” but less studied, chemotherapy agents [6].
- Meregalli described some of the mechanisms related to bortezomib-induced peripheral neuropathy. Bortezomib is a proteasome inhibitor chemotherapy drug that was also recently considered to able to dysregulate tubulin disassembly and consequently alter axonal transport. However, other actors seem to also be involved in this story [7].
- Other widely studied antitubulinic chemotherapy drugs are taxanes. Velasco and Bruna reviewed some of the most updated knowledge on the real incidence, pathophysiology, clinical features, and predisposing factors related to the development of taxane-induced peripheral neuropathy [8].
- Not only taxanes, but also platinum compounds, vinka alkaloids, and proteasome inhibitors can induce a mitochondrial dysregulation in peripheral nervous systems during chemotherapy. Canta and collaborators reported that the dysfunction of calcium signalling pathways and the production of reactive oxygen species could determine abnormal membrane potentials and neuronal excitability. Genetic changes in mitochondrial DNA also lead to gradual neuronal energy failure [9].
- Last, but not least, Stansley and Yamamoto reported the latest findings on the safety of l-Dopa for the treatment of Parkinson’s Disease. Since dopamine is produced by l-dopa in part by serotonin neurons, an increase in dopamine seems to cause oxidative stress and damage serotonin neurons. l-dopa also caused deficits in serotonin neurotransmission controlling mood and cognition, warranting some severe side effects observed in Parkinsons’ patients [10].
References
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- Meregalli, C. An Overview of Bortezomib-Induced Neurotoxicity. Toxics 2015, 3, 294–303. [Google Scholar] [CrossRef]
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Carozzi, V.A.; Cavaletti, G. Toxicities of Therapeutic Agents Used in Medicine. Toxics 2016, 4, 14. https://doi.org/10.3390/toxics4030014
Carozzi VA, Cavaletti G. Toxicities of Therapeutic Agents Used in Medicine. Toxics. 2016; 4(3):14. https://doi.org/10.3390/toxics4030014
Chicago/Turabian StyleCarozzi, Valentina Alda, and Guido Cavaletti. 2016. "Toxicities of Therapeutic Agents Used in Medicine" Toxics 4, no. 3: 14. https://doi.org/10.3390/toxics4030014