Abstract
Polyneuropathy is defined as a simultaneous malfunction of several peripheral nerves, which could be a side effect of cancer therapy; however, this is reported to occur rarely and difficult to prove. The purpose of the study was to introduce for the first time the calorimetry in the diagnosis of neuropathy in an experimental animal model. The study was inspired by the forensic investigation of a 53-year-old cancer survival female patient, in whose case the development of polyneuropathy could have been caused by cyclophosphamide therapy. Adult guinea pigs were injected intraperitoneally with the dose of cyclophosphamide that comparable to the human dosage. Animals were euthanized; nerve and muscle samples were analyzed by a SETARAM Micro calorimeter. The denaturation temperatures were measured and the calorimetric enthalpies were calculated based on the areas under thermal absorption curves. The thermal denaturation of the samples decreased and the calorimetric enthalpy increased, depending on the therapeutic cyclophosphamide doses. The nerves were more sensitive to chemotherapy, compared to the muscles. The toxic effects of cyclophosphamide on peripheral nerves and muscles can be measured and analyzed by calorimetry, which effects were found dose dependent.
This is a preview of subscription content, log in via an institution to check access.
References
Singleton JR, Smith AG. The diabetic neuropathies: practical and rational therapy. Semin Neurol. 2012;32:96–203.
Chopra K, Tiwari V. Alcoholic neuropathy: possible mechanisms and future treatment possibilities. Br J Clin Pharmacol. 2012;73:348–62.
Manji H. Toxic neuropathy. Curr Opin Neurol. 2011;24:484–90.
Rudnicki SA, Dalmau J. Paraneoplastic syndromes of the peripheral nerves. Curr Opin Neurol. 2005;18:598–603.
Koike H, Tanaka F, Sobue G. Paraneoplastic neuropathy: wide-ranging clinico-pathological manifestations. Curr Opin Neurol. 2011;24:504–10.
Rosenfeld MR, Dalmau J. Update on paraneoplastic neurologic disorders. Oncologist. 2010;15:603–17.
Leitch MM, Sherman WH, Brannagan TH. Distal acquired demyelinating symmetric polyneuropathy progressing to classic chronic inflammatory demyelinating polyneuropathy and response to fludarabine and cyclophosphamide. Muscle Nerve. 2012. doi:10.1002/mus.23629.
Kemler P. Neuropatiák. New York: Springer; 1996 (in Hungarian).
Wiegand N, Vámhidy L, Patczai B, Dömse E, Than P, Kereskai L, Lőrinczy D. Differential scanning calorimetric examination of transverse carpal ligament in carpal tunnel disease. J Thermal Anal Calorim. 2009;95:793–6.
Wiegand N, Vámhidy L, Patczai B, Dömse E, Than P, Kereskai L, Lőrinczy D. Differential scanning calorimetric examination of the degenerated human palmar aponeurosis in Dupuytren disease. J Thermal Anal Calorim. 2009;95:797–800.
Bálint G, Than P, Domán I, Wiegand N, Horváth G, Lőrinczy D. Calorimetric examination of the human meniscus. J Thermal Anal Calorim. 2009;95:759–61.
Wiegand N, Vámhidy L, Lőrinczy D. Differential scanning calorimetric examination of ruptured lower limb tendons in human. J Thermal Anal Calorim. 2010;101:487–92.
Wiegand N, Vámhidy L, Kereskai L, Lőrinczy D. Differential scanning calorimetric examination of the ruptured achilles tendon in human. Thermochim Acta. 2010;498:7–10.
Naumov I, Wiegand N, Patczai B, et al. Differential scanning calorimetric examination of the human hyaline cartilage of the femoral head after femoral neck fracture. J Thermal Anal Calorim. 2011;102:1–7.
Naumov I, Lőrinczy D, Vámhidy L, Than P, Wiegand N. Differential scanning calorimetric examination of the interfacial membrane in failed hip joint replacements. J Thermal Anal Calorim. 2012;109:783–7.
Fürst ZS. Gyógyszertan. Emilia-Romagna: Medicina; 1998 (in Hungarian).
Lőrinczy D, Belágyi J. Effects of nucleotide on skeletal muscle myosin unfolding in myofibrils by DSC. Biochem Biophys Res Commun. 1995;217:592–8.
Belágyi J, Lőrinczy D. Internal motions in the catalytic domain of myosin heads in muscle fibres effects of ADP and ATP. Biochem Biophys Res Commun. 1996;219:936–40.
Lőrinczy D, Belágyi J. Comparative study of myosins in solutions and supramolecular complexes. Effect of nucleotides. Thermochim Acta. 1997;296:161–8.
Lőrinczy D, Hartvig N, Belágyi J. Nucleotide analogue induces global and local changes in muscle fibres. J Thermal Anal Calorim. 2001;64:651–8.
Dergez T, Könczöl F, Farkas N, Belagyi J, Lőrinczy D. DSC study of glycerol-extracted muscle fibers in intermediate states of ATP hydrolysis. J Thermal Anal Calorim. 2005;80:445–9.
Lőrinczy D, Belagyi J. Intermediate states of myosin head during ATP hydrolysis cycle in psoas muscle fibres by EPR and DSC (a review). J Thermal Anal Calorim. 2007;90:611–21.
Dergez T, Lőrinczy D, Könczöl F, Farkas N, Belagyi J. Differential scanning calorimetry study of glycerinated rabbit psoas muscle fibres in intermediate state of ATP hydrolysis. BMC Struct Biol. 2007;7:41–50.
Gazsó I, Kránicz J, Bellyei Á, Lőrinczy D. DSC analysis of the abnormalities of human leg skeletal muscles: a preliminary study. Thermochim Acta. 2003;402:117–22.
Wiegand N, Vámhidy L, Patczai B, Dömse E, Kereskai L, Lőrinczy D. Differential scanning calorimetric examination of the human skeletal muscle in a compartment syndrome of the lower extremities. J Thermal Anal Calorim. 2009;98:177–82.
Acknowledgments
This study was supported by Grant OTKA C272 (for D. L.).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Könczöl, F., Wiegand, N., Nöt, L.G. et al. Examination of the cyclophosphamide-induced polyneuropathy on guinea pig sciatic nerve and gastrocnemius muscle with differential scanning calorimetry. J Therm Anal Calorim 115, 2239–2243 (2014). https://doi.org/10.1007/s10973-013-3179-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10973-013-3179-z