BGP-15, a hydroximic acid derivative, protects against cisplatin- or taxol-induced peripheral neuropathy in rats

• Published in: Toxicology and applied pharmacology Vol. 190; no. 1; pp. 9 - 16
• Main Authors: Bárdos, G, Móricz, K, Jaszlits, L, Rabloczky, G, Tory, K, Rácz, I, Bernáth, S, Sümegi, B, Farkas, B, Literáti-Nagy, B, Literáti-Nagy, P
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 01.07.2003; Elsevier
• Subjects: Animals; Antineoplastic Agents - antagonists & inhibitors; Antineoplastic Agents - toxicity; Antineoplastic Agents, Phytogenic - antagonists & inhibitors; Antineoplastic Agents, Phytogenic - toxicity; BGP-15; Biological and medical sciences; Body Weight - drug effects; Cell Survival - drug effects; Cisplatin; Cisplatin - antagonists & inhibitors; Cisplatin - toxicity; Drug toxicity and drugs side effects treatment; Electrophysiology; Male; Medical sciences; Modulation of PARP activity; Motor Neurons - drug effects; Nerve conduction velocity; Neural Conduction - drug effects; Neurons, Afferent - drug effects; Oximes - pharmacology; Paclitaxel - antagonists & inhibitors; Paclitaxel - toxicity; Peripheral Nervous System Diseases - chemically induced; Peripheral Nervous System Diseases - prevention & control; Peripheral sensory neuropathy; Pharmacology. Drug treatments; Piperidines - pharmacology; Poly(ADP-ribose) polymerase (PARP) enzyme; Prevention of neuropathy; Rats; Taxol; Toxic effects of antitumor drugs; Toxicity: nervous system and muscle; Toxic effects of antitumor drugs; Poly(ADP-ribose) polymerase (PARP) enzyme; Taxol; Nerve conduction velocity; Prevention of neuropathy; BGP-15; Peripheral sensory neuropathy; Modulation of PARP activity; Cisplatin; Antineoplastic agent; Rat; Toxicity; Glycosyltransferases; Peripheral neuropathy; Prevention; ADP-ribosyltransferase; Peripheral nerve disease; Nervous system diseases; Enzyme; Transferases; Rodentia; Enzyme inhibitor; NAD; Vertebrata; Mammalia; Animal; Pentosyltransferases
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/S0041-008X(03)00155-8

The neuroprotective effect of BGP-15 against peripheral sensory neuropathy was studied in rats that were exposed to short-term cisplatin or taxol administration. The changes of nerve conduction velocity were determined in situ after treating the Wistar rats with BGP-15 (50, 100, and 200 mg/kg po daily doses throughout the experiment), cisplatin (1.5 mg/kg ip daily dose for 5 days), or taxol (5.0 mg/kg ip daily dose every other day in a 10-day interval) alone or giving the test compound in combination with cisplatin or taxol. Electrophysiological recordings were carried out in vivo by stimulating the sciatic nerve at both sciatic notch and ankle site. Neither motor nor sensory nerve conduction velocity was altered by any dose level of BGP-15 tested. Both anticancer drugs decreased the sensory nerve conduction velocity (SNCV). BGP-15 treatment prevented the impairment of SNCV either in part or totally in the cisplatin- or taxol-treated groups. This neuroprotective potential of BGP-15 could be well correlated with its recently described poly(ADP-ribose) polymerase- inhibitory effect and its ability to protect against the damages induced by the increased level of reactive oxygen species in response to anticancer treatment.