Delayed treatment with vitamin C and N-Acetyl-L-Cysteine (NAC) protects Schwann cells without compromising the anti-myeloma activity of bortezomib
– Source: International Journal of Hematology, online Apr 28, 2011
By Ayako Nakano, et al.
[Note: The cancer drug bortezomib causes peripheral neuropathy – damage to nerve cells in the extremities (e.g., feet), a condition associated with diabetes. Schwann cells protect (wrap themselves around) the long tails of the nerve cells (axons) which conduct electrical impulses in the nervous system. Thus, in protecting and bolstering the Schwann cells the supplemental vitamin C and NAC protected the integrity of the nerves.]
Bortezomib-induced peripheral neuropathy (BIPN) emerges as a disabling adverse effect. As rat models for BIPN have demonstrated damage in nerve Schwann cells, we screened for cytoprotective agents to devise a method of rescuing Schwann cells from the cytotoxic effects of bortezomib without compromising its anti-myeloma [anti-cancer] effects.
Schwann cells underwent macroautophagy along with cytoplasmic inclusion body and vacuole formation, and appeared much less susceptible to bortezomib-induced cytotoxicity than did myeloma cells.
Vitamin C or N-acetyl-L-cysteine (NAC) achieved near-complete rescue of Schwann cells treated with bortezomib at 30 nM or less, and these agents in combination are able to cooperatively inhibit the morphological changes and the cytotoxicity in Schwann cells with higher doses of bortezomib.
The delayed addition of vitamin C and/or NAC after the exposure to bortezomib alleviated the cytotoxicity in Schwann cells but not myeloma cells. These results suggest that delayed treatment with these agents may be instrumental in prophylaxis of [protection against] Bortezomib-induced peripheral neuropathy.
Source: International Journal of Hematology, Apr 28, 2011. Nakano A, Abe M, Oda A, Amou H, et al. Department of Medicine and Bioregulatory Sciences, University of Tokushima Graduate School of Medicine, Tokushima, Japan. [Email: email@example.com]