Mechanisms of Chemotherapy-Induced Neurotoxicity

Waś, Halina; Borkowska, Agata; Bagüés, Ana; Tu, Longlong; Liu, Julia Y.H.; Lu, Zhonghua; Rudd, John A.; Nurgali, Kulmira; Abalo, Raquel

doi:10.3389/fphar.2022.750507

Cited by 78 publications

(54 citation statements)

References 363 publications

(449 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The risk of neurotoxicity may be increased by high doses or prolonged therapy. Neurotoxicity can occur days or weeks after starting treatment, with recovery usually weeks or months after stopping treatment [ 161 ]. Neurological effects are usually less common and severe than with vincristine.…”

Section: Therapeutic Limitationsmentioning

confidence: 99%

Anticancer potential of alkaloids: a key emphasis to colchicine, vinblastine, vincristine, vindesine, vinorelbine and vincamine

et al. 2022

View full text Add to dashboard Cite

Cancer, one of the leading illnesses, accounts for about 10 million deaths worldwide. The treatment of cancer includes surgery, chemotherapy, radiation therapy, and drug therapy, along with others, which not only put a tremendous economic effect on patients but also develop drug resistance in patients with time. A significant number of cancer cases can be prevented/treated by implementing evidence-based preventive strategies. Plant-based drugs have evolved as promising preventive chemo options both in developing and developed nations. The secondary plant metabolites such as alkaloids have proven efficacy and acceptability for cancer treatment. Apropos, this review deals with a spectrum of promising alkaloids such as colchicine, vinblastine, vincristine, vindesine, vinorelbine, and vincamine within different domains of comprehensive information on these molecules such as their medical applications (contemporary/traditional), mechanism of antitumor action, and potential scale-up biotechnological studies on an in-vitro scale. The comprehensive information provided in the review will be a valuable resource to develop an effective, affordable, and cost effective cancer management program using these alkaloids.

show abstract

Section: Therapeutic Limitationsmentioning

confidence: 99%

Anticancer potential of alkaloids: a key emphasis to colchicine, vinblastine, vincristine, vindesine, vinorelbine and vincamine

et al. 2022

View full text Add to dashboard Cite

show abstract

“…This results in an increase in ROS levels (reactive oxygen species) and oxidative stress. Consequently, a complex cascade of events leads to the degeneration of DRG neurons causing neuropathy (33)(34)(35). Moreover, studies showed that oxaliplatin increased the levels of chemokines, C-X3-C motif chemokine ligand 1 (CX3CL1) and C-X3-C motif chemokine ligand 12 (CXCL12), and their ligands, chemokine ligands (CCLs), in DRG neurons thus enhancing peripheral neuropathy.…”

Section: Mechanisms Of Chemotherapy-induced Peripheral Neuropathymentioning

confidence: 99%

Pathophysiology and Therapeutic Perspectives for Chemotherapy-induced Peripheral Neuropathy

et al. 2022

View full text Add to dashboard Cite

Chemotherapy-induced peripheral neuropathy (CIPN) develops as a challenging nerve-damaging adverse effect of anticancer drugs used in chemotherapy. The disorder may require a chemotherapy dose reduction and a cessation of administration of chemotherapeutic drugs. Its principal sensory symptoms include, tingling, and numbness in the hands and feet. Severe pain can be encompassed among clinical manifestations. CIPN affects dramatically the patient's quality of life (QoL). Pain and sensory symptoms may occur for months, or even years after the termination of chemotherapeutic drugs. Although many pharmacological and non-pharmacological therapeutic approaches have been tested to overcome these symptoms, there is currently no standardized treatment for CIPN. According to current guidelines, Duloxetine is the only recommended agent for painful neuropathic symptoms. Therefore, finding effective therapies for CIPN is mandatory. The aim of this review was to dissect CIPN, the target and immunotherapy-based approaches to this disorder, as well as to offer new insights for new therapeutic perspectives.Chemotherapy-induced peripheral neurotoxicity (CIPN) is a common side effect of cancer therapy, affecting approximately 40% of patients receiving active treatment (1). CIPN is mainly characterized by sensory symptoms in a typical distribution (i.e., 'stocking and glove') that first appear in the toes and fingers and then spread to the legs and arms. Patients suffering from a more severe form of CIPN, also show fatigue, pain, and gastrointestinal disorder. Interestingly, patient age, impaired renal function, exposure to other neurotoxic chemotherapeutic agents, or other disorders represent predisposing risk factors of CIPN (2). The pathophysiology of CIPN is very complex and relies on several processes depending on the type of chemotherapy used, although the underlying molecular mechanisms are still unknown (1-4). Many chemotherapy agents are associated with indirect or direct neurotoxicity and CIPN, including platinum derivates, taxanes, vinca alkaloids, proteasome inhibitors, Bortezomib, immunomodulatory agents and several classes of biological agents such as targeted therapies, multikinase inhibitors, immunotherapy, and antibody-drug conjugates (5). Moreover, cognitive impairment may arise from anticancer treatments.The most common clinical manifestation of CIPN is sensory axonal neuropathy with motor and autonomic involvement. Specifically, depression, anxiety, and cognitive disorder, represent typical central symptoms. CIPN is a peripheral neurotoxicity. Cognitive impairment, commonly termed chemo-brain, affects cancer patients treated with chemotherapy agents (CNS toxicity) (6). A significant role of neuroinflammation, blood-brain barrier disruption, defective neurogenesis, and oxidative stress has been postulated in causing cognitive deficits (7).Persistent CIPN symptoms are associated with an increased risk of falling, disability, and psychosocial distress (8). Moreover, as symptoms have been reported to be chemotherapy ...

show abstract

“…Almost all chemotherapy agents, despite their disparate chemical structures, can induce nausea and vomiting, suggesting a generalized neuronal action [ 14 ]. Among them, vincristine is known for its autonomic and gastrointestinal side effects [ 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Ginger Constituent 6-Shogaol Attenuates Vincristine-Induced Activation of Mouse Gastroesophageal Vagal Afferent C-Fibers

Patil

Huang

et al. 2022

Molecules

View full text Add to dashboard Cite

Chemotherapeutic agent-induced nausea and vomiting are the severe adverse effects that are induced by their stimulations on the peripheral and/or central emetic nerve pathways. Even though ginger has been widely used as an herbal medicine to treat emesis, mechanisms underlying its neuronal actions are still less clear. The present study aimed to determine the chemotherapeutic agent vincristine-induced effect on gastroesophageal vagal afferent nerve endings and the potential inhibitory role of ginger constituent 6-shogaol on such response. Two-photon neuron imaging studies were performed in ex vivo gastroesophageal-vagal preparations from Pirt-GCaMP6 transgenic mice. Vincristine was applied to the gastroesophageal vagal afferent nerve endings, and the evoked calcium influxes in their intact nodose ganglion neuron somas were recorded. The responsive nodose neuron population was first characterized, and the inhibitory effects of 5-HT3 antagonist palonosetron, TRPA1 antagonist HC-030031, and ginger constituent 6-shogaol were then determined. Vincristine application at gastroesophageal vagal afferent nerve endings elicited intensive calcium influxes in a sub-population of vagal ganglion neurons. These neurons were characterized by their positive responses to P2X2/3 receptor agonist α,β-methylene ATP and TRPA1 agonist cinnamaldehyde, suggesting their nociceptive placodal nodose C-fiber neuron lineages. Pretreatment with TRPA1 selective blocker HC-030031 inhibited vincristine-induced calcium influxes in gastroesophageal nodose C-fiber neurons, indicating that TRPA1 played a functional role in mediating vincristine-induced activation response. Such inhibitory effect was comparable to that from 5-HT3 receptor antagonist palonosetron. Alternatively, pretreatment with ginger constituent 6-shogaol significantly attenuated vincristine-induced activation response. The present study provides new evidence that chemotherapeutic agent vincristine directly activates vagal nodose nociceptive C-fiber neurons at their peripheral nerve endings in the upper gastrointestinal tract. This activation response requires both TRPA1 and 5-HT3 receptors and can be attenuated by ginger constituent 6-shogaol.

show abstract

Mechanisms of Chemotherapy-Induced Neurotoxicity

Cited by 78 publications

References 363 publications

Anticancer potential of alkaloids: a key emphasis to colchicine, vinblastine, vincristine, vindesine, vinorelbine and vincamine

Anticancer potential of alkaloids: a key emphasis to colchicine, vinblastine, vincristine, vindesine, vinorelbine and vincamine

Pathophysiology and Therapeutic Perspectives for Chemotherapy-induced Peripheral Neuropathy

Ginger Constituent 6-Shogaol Attenuates Vincristine-Induced Activation of Mouse Gastroesophageal Vagal Afferent C-Fibers

Contact Info

Product

Resources

About