Bortezomib-induced peripheral neurotoxicity: A neurophysiological and pathological study in the rat

Cavaletti, Guido; Gilardini, Alessandra; Canta, A; Rigamonti, L; Rodriguez-Menendez, Virginia; Ceresa, C; Marmiroli, P; Bossi, M; Oggioni, N; D’Incalci, Maurizio; Coster, R. De

doi:10.1016/j.expneurol.2006.11.010

Cited by 238 publications

(242 citation statements)

References 30 publications

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“…Second, we observed a mild impairment of neuromuscular transmission in the 4w-Bz control group (but not in the 8w-Bz Control group) in comparison with the saline-treated control group. This effect possibly indicates transient nerve damage similar to the bortezomib-induced polyneuropathy (26,40). Arguably, the weight loss in control animals was caused by an effect of proteasome inhibition on the gastrointestinal tract, which has been seen in patients (41).…”

Section: Discussionmentioning

confidence: 98%

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Proteasome Inhibition with Bortezomib Depletes Plasma Cells and Autoantibodies in Experimental Autoimmune Myasthenia Gravis

Gomez

Vrolix

Martínez‐Martínez

et al. 2011

The Journal of Immunology

124

100

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Bortezomib, an inhibitor of proteasomes, has been reported to reduce autoantibody titers and to improve clinical condition in mice suffering from lupus-like disease. Bortezomib depletes both short- and long-lived plasma cells; the latter normally survive the standard immunosuppressant treatments targeting T and B cells. These findings encouraged us to test whether bortezomib is effective for alleviating the symptoms in the experimental autoimmune myasthenia gravis (EAMG) model for myasthenia gravis, a disease that is characterized by autoantibodies against the acetylcholine receptor (AChR) of skeletal muscle. Lewis rats were immunized with saline (control, n = 36) or Torpedo AChR (EAMG, n = 54) in CFA in the first week of an experimental period of 8 wk. After immunization, rats received twice a week s.c. injections of bortezomib (0.2 mg/kg in saline) or saline injections. Bortezomib induced apoptosis in bone marrow cells and reduced the amount of plasma cells in the bone marrow by up to 81%. In the EAMG animals, bortezomib efficiently reduced the rise of anti-AChR autoantibody titers, prevented ultrastructural damage of the postsynaptic membrane, improved neuromuscular transmission, and decreased myasthenic symptoms. This study thus underscores the potential of the therapeutic use of proteasome inhibitors to target plasma cells in Ab-mediated autoimmune diseases.

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Section: Discussionmentioning

confidence: 98%

“…Two weekly doses of 0.2 mg/kg bortezomib solution were administered s.c., which is considered the highest dose to use without having increased mortality rates or severe side effects in rats (10,25,26). Control and EAMG groups were subdivided into three treatment regimes each (Table I).…”

Section: Experimental Design and Administration Of Drugsmentioning

confidence: 99%

Proteasome Inhibition with Bortezomib Depletes Plasma Cells and Autoantibodies in Experimental Autoimmune Myasthenia Gravis

Gomez

Vrolix

Martínez‐Martínez

et al. 2011

The Journal of Immunology

124

100

View full text Add to dashboard Cite

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“…A multifactorial pathogenesis for BiPN seems likely, with suggested mechanisms including blockade of nerve-growthfactor-mediated neuronal survival through inhibition of the activation of nuclear factor κB (NFκB), 5 damage to mitochondria and the endoplasmic reticulum through activation of apoptosis, 6 dysregulation of mitochondrial calcium homoeostasis, 7 autoimmune factors, interference with mRNA processing, and translation 8 and inflammation. [9][10] A number of studies, including a report by our own group, have looked at the pharmacogenetic characterization of BiPN.…”

Section: Introductionmentioning

confidence: 99%

Genetic factors underlying the risk of bortezomib induced peripheral neuropathy in multiple myeloma patients

Corthals¹,

Kuiper²,

Johnson³

et al. 2011

Haematologica

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“…In accordance with this observation, calcium chelating agents are able to reverse paclitaxel-evoked pain [21], and acetyl-l-carnitine, which prevents mPTP opening [22], reduces the development of paclitaxel-induced neuropathic pain [23]. Administration of bortezomib leads to intracytoplasmatic vacuolization in dorsal root ganglia (DRG) satellite cells, probably due to mitochondrial and endoplasmic reticulum enlargement [24]. All these intracellular modifications are probably related to the ability of bortezomib to activate mitochondrial-based apoptotic pathways, including activation of caspases [25] and dysregulation of calcium homeostasis [26].…”

Section: Introductionmentioning

confidence: 70%

Transient Receptor Potential Channels in Chemotherapy-Induced Neuropathy

Nassini¹,

Benemei²,

Fusi³

et al. 2013

TOPAINJ

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Chemotherapy-Induced Peripheral Neuropathy (CIPN) is a common dose-limiting side effect of many chemotherapeutic drugs, including platinum-based compounds (e.g., cisplatin and oxaliplatin), taxanes (e.g., paclitaxel), vinca alkaloids (e.g., vincristine), and the first-in-class proteasome inhibitor, bortezomib. Among the various sensory symptoms of CIPN, paresthesia, dysesthesia, spontaneous pain, and mechanical and thermal hypersensitivity are prominent. Inflammation, oxidative stress, loss of intraepidermal nerve fibers, modifications of mitochondria, and various ion channels alterations are part of the several mechanisms contributing to CIPN. Because attempts to mitigate chemotherapeutic-induced acute neuronal hyperexcitability and the subsequent peripheral neuropathy have yielded unsatisfactory results, a more in-depth understanding of the mechanism(s) responsible for the neurotoxic action of anticancer drugs is required.Some members of the transient receptor potential (TRP) family of channels, as the TRPV1 and TRPV4 (vanilloid), TRPA1 (ankyrin) and TRPM8 (melastatin) are expressed on the plasma membrane of primary sensory neurons (nociceptors), where they are activated by an unprecedented series of physical and chemical stimuli. There is evidence that TRPV1, TRPV4, TRPA1 and TRPM8 are prominent contributors of mechanical and thermal hypersensitivity in models of CIPN. In particular, in vitro and in vivo studies have pointed out the unique role of TRPA1 and oxidative stress in the mechanism responsible for cold and mechanical hyperalgesia in rodent models of CIPN.

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Bortezomib-induced peripheral neurotoxicity: A neurophysiological and pathological study in the rat

Cited by 238 publications

References 30 publications

Proteasome Inhibition with Bortezomib Depletes Plasma Cells and Autoantibodies in Experimental Autoimmune Myasthenia Gravis

Proteasome Inhibition with Bortezomib Depletes Plasma Cells and Autoantibodies in Experimental Autoimmune Myasthenia Gravis

Genetic factors underlying the risk of bortezomib induced peripheral neuropathy in multiple myeloma patients

Transient Receptor Potential Channels in Chemotherapy-Induced Neuropathy

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