ABSTRACT
We investigated full-field ERGs in beagle dogs using a contact lens electrode with built-in LED. Experiment 1 was performed to determine the appropriate conditions for stimulus intensity and background illumination. We found that full-field ERGs could be recorded under the following conditions: stimulus intensity: -2.5logcd*s/m(2) in rod responses (RRs), 1.2logcd*s/m(2) in maximal responses (MRs), oscillatory potentials (OPs), cone responses (CRs), 30-Hz flicker responses (FRs), and background illumination: more than 25cd/m(2) in CRs and FRs. Experiment 2 was performed to apply full-field ERGs in beagle dogs to the detection of retinal toxicities. A dog was given one 30mg/kg dose of sodium iodate (NaIO(3)) intravenously. ERGs were recorded before administration and 1, 3, 5, 8, 24h, 7 and 14 days after administration of NaIO(3). The RRs disappeared completely at 1h when MRs and OPs decreased. On the other hand, CRs and FRs were recorded even at 8h. All responses disappeared at 24h. These findings indicate that retinal toxicity by NaIO(3) is first expressed in rods, followed by cones. These results suggest that full-field ERGs in beagle dogs using an LED contact lens can be used to evaluate toxic effects on rods and cones separately, with the potential to prove more useful than conventional methods for toxicological assessments of developing pharmaceuticals, and can be applied to it.
Subject(s)
Contact Lenses , Electroretinography/instrumentation , Light , Toxicity Tests/instrumentation , Animals , Dogs , Drug-Related Side Effects and Adverse Reactions , Electrodes , Electroretinography/methods , Iodates/adverse effects , Male , Toxicity Tests/methodsABSTRACT
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.
Subject(s)
Drug-Related Side Effects and Adverse Reactions , Ethambutol/toxicity , Evoked Potentials, Visual/drug effects , Visual Cortex/drug effects , Animals , Antitubercular Agents/toxicity , Dose-Response Relationship, Radiation , Drug Administration Schedule , Evoked Potentials, Visual/radiation effects , Male , Photic Stimulation/methods , Rats , Rats, Long-Evans , Reaction Time/drug effects , Reaction Time/radiation effects , Space Perception/drug effects , Space Perception/radiation effects , Time Factors , Visual Cortex/radiation effectsABSTRACT
We determined whether visually evoked cortical potentials obtained using checker patterns (P-VECPs) and albino rats would reveal visual damage induced by ethambutol (EB). Findings were compared in cases of detection of visual damage between by P-VECPs and by flash visually evoked cortical potentials (F-VECPs). Twelve adult albino male Crj:CD(SD)IGS rats were grouped into four, three per group: control, 250PS, 500PS, and 500SC groups. In the 250PS and 500PS groups, rats were administered EB orally for the first 2 weeks and then subcutaneously for the second 2 weeks to 250 and 500 mg/kg, respectively. In the 500SC group, rats were given 500 mg/kg of EB subcutaneously for 4 weeks. Rats in the control group were given the vehicle orally for the first 2 weeks and then subcutaneouly for the second 2 weeks. P-VECPs and F-VECPs were carried out prior to initiation of drug administration and at the 1st, 2nd, 3rd, and 4th weeks of the administration. Prolongation of P1 latency in the P-VECPs was evident in both the 500PS and the 500SC groups at the 4th week, while no marked changes were observed in the F-VECPs. Thus, P-VECPs in albino rats can detect visual damage induced by EB even when F-VECPs cannot do so. These studies suggest that P-VECPs are useful for evaluating the visual toxicity of drugs.