Evaluation of SR-2508 induced neurotoxicity and myotoxicity in rats using brainstem auditory evoked potentials and the posterior auricular muscle response.

Brainstem auditory evoked potential (BAEPs) and a middle latency component attributed to the posterior auricular muscle response (PAMR) to an intense auditory stimulus were used to measure the onset of neurotoxic and myotoxic effects in rats after chronic exposure to the radiosensitizer SR-2508. The rats received intraperitoneal injections of SR-2508, 500 mg/kg, 5 days/week for 6 weeks. BAEP and PAMR were measured after 10, 20, and 30 injections and 4 weeks after the drug treatment was stopped. A significant neurotoxic effect was observed: After 10 injections of SR-2508, latency of the fourth positive (P4) component of the BAEP, which is thought to represent activity from the superior olivary nuclei, increased from baseline levels, and a further increase was measured after 30 injections. Four weeks after drug treatment was stopped, P4 latency had not returned to baseline levels, indicating permanent injury. PAMR latency was also increased after 10 injections of SR-2508, but increased no further during the drug treatment period. Four weeks after the last injection, PAMR latencies had returned to pretreatment levels, indicating that the myotoxic effects of SR-2508 were reversible.