Back to Search
Start Over
Docetaxel-induced peripheral neuropathy: protective effects of dihydroprogesterone and progesterone in an experimental model.
- Source :
-
Journal of the peripheral nervous system : JPNS [J Peripher Nerv Syst] 2009 Mar; Vol. 14 (1), pp. 36-44. - Publication Year :
- 2009
-
Abstract
- Peripheral neurotoxicity is a frequent complication limiting docetaxel chemotherapy in patients with cancer. We developed an experimental model that closely mimics the course of neuropathy in patients, aiming to investigate both the mechanisms of neurotoxicity at biochemical, functional and morphological levels and the potential neuroprotective role of neuroactive steroids. We demonstrated that treatment with dihydroprogesterone (DHP) or progesterone (P) counteracts docetaxel-induced neuropathy, preventing nerve conduction and thermal threshold changes, and degeneration of skin nerves in the foodpad. Neuroactive steroids also counteract the changes in gene expression of several myelin proteins and calcitonin gene-related peptide induced by docetaxel in sciatic nerve and lumbar spinal cord, respectively. Most nerve abnormalities observed during the treatment with docetaxel spontaneously recovered after drug withdrawal, similarly to what occurs in patients. However, results of midterm follow-up experiments indicated that animals cotreated with DHP or P have a faster recovery of the neuropathy compared with docetaxel-treated rats. Our study confirmed that neuroactive steroids exert a protective effect on peripheral nerves at different levels, suggesting that they might represent a new therapeutic frontier for patients with chemotherapy-induced neuropathy.
- Subjects :
- Analysis of Variance
Animals
Body Weight drug effects
Disease Models, Animal
Docetaxel
Male
Myelin Basic Protein genetics
Myelin Basic Protein metabolism
Myelin P0 Protein genetics
Myelin P0 Protein metabolism
Myelin Proteins genetics
Myelin Proteins metabolism
Nerve Fibers pathology
Neural Conduction physiology
Pain Threshold drug effects
Peripheral Nervous System Diseases physiopathology
Rats
Rats, Inbred F344
Sciatic Nerve pathology
Taxoids pharmacology
20-alpha-Dihydroprogesterone pharmacology
Gene Expression Regulation drug effects
Neural Conduction drug effects
Neuroprotective Agents pharmacology
Peripheral Nervous System Diseases chemically induced
Peripheral Nervous System Diseases prevention & control
Progesterone pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1529-8027
- Volume :
- 14
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of the peripheral nervous system : JPNS
- Publication Type :
- Academic Journal
- Accession number :
- 19335538
- Full Text :
- https://doi.org/10.1111/j.1529-8027.2009.00204.x