title: P-VECP can reveal visual toxicity in pigmented rats of repeated doses of ethambutol.
abstract: We determined if pattern visually evoked cortical potentials (P-VECPs) in pigmented rats would reveal visual toxicity induced by a drug even when in cases of repeated doses. We obtained appropriate conditions of P-VECPs measurement; the spatial frequency, 0.16 cycle/degree; the mean stimulation luminance, 25 cd/m(2); and the stimulation frequency, 2 Hz. Twelve adult male pigmented rats (Iar: Long-Evans), weighing 210-301 g, were grouped into two (six per group): the control and the ethambutol (EB) 500 mg/kg administered groups. In the EB 500 mg/kg group, the rats were administered EB subcutaneously once daily for 6 weeks. Rats in the control group were given the vehicle subcutaneously once daily for 6 weeks. P-VECPs were carried out prior to initiation of drug administration and at the first, second, third, fourth, and sixth week of the administration. Prolongation of P1 latency in the P-VECPs was evident in the EB 500 mg/kg at fourth and sixth weeks, and there were no marked changes in the control group and no marked changes in P1N1 amplitude in either group. These findings suggest that P-VECPs in pigmented rats can detect chemically induced visual toxicity even in cases of repeated dosing of a drug. This approach is useful for evaluating the visual toxicity of drugs given repeatedly.
authors.affiliation: Toxicology Laboratory, Medicinal Laboratories, Taisho Pharmaceutical Company, Limited, 403 Yoshino-cho 1, Kita-ku, Saitama-shi, Saitama 331-9530, Japan. shoji.sasaki@po.rd.taisho.co.jp
authors.forename: Shoji
authors.initials: S
authors.lastname: Sasaki
authors.forename: Kumiko
authors.initials: K
authors.lastname: Yagi
authors.forename: Hiroto
authors.initials: H
authors.lastname: Miyata
authors.forename: Isamu
authors.initials: I
authors.lastname: Nakamura
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Iwaki
authors.forename: Masaaki
authors.initials: M
authors.lastname: Kimura
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000633:toxicity; D004307:Dose-Response Relationship, Radiation; D004334:Drug Administration Schedule; D064420:Drug-Related Side Effects and Adverse Reactions; D004977:Ethambutol / Q000633:toxicity*; D005074:Evoked Potentials, Visual / Q000187:drug effects* / Q000528:radiation effects; D008297:Male; D010775:Photic Stimulation / Q000379:methods; D051381:Rats; D020318:Rats, Long-Evans; D011930:Reaction Time / Q000187:drug effects / Q000528:radiation effects; D013028:Space Perception / Q000187:drug effects / Q000528:radiation effects; D013997:Time Factors; D014793:Visual Cortex / Q000187:drug effects* / Q000528:radiation effects
chemical_list: D000995:Antitubercular Agents; D004977:Ethambutol