2-amino-4-hydroxy-6-formylpteridine and Disease-Models--Animal

Potentiation of noise-induced hearing loss (NIHL) by specific chemical contaminants and therapeutic drugs represents a distinct public health risk. Prediction of chemicals that yield such potentiation has not been successful because such agents differ markedly in structure. One mechanism for this potentiation that has garnered support is oxidative injury to the cochlea. Thus far, limited data have been published in support of this hypothesis. The current experiment was designed to further test this model using two antioxidant compounds, lipoic acid (LA) and 6-formylpterin (6-FP), and determine whether they would block potentiation of NIHL resulting from simultaneous exposures to carbon monoxide (CO) and noise in rats. Neither CO nor noise exposure at the intensity and duration selected produce persistent auditory impairment by themselves. Different groups of rats were exposed to noise alone centered at 8.0 kHz (105 dB) for 2 hours or to combined CO + noise treatment consisting of CO exposure for 1.5 hours and then exposure to CO + noise for 2 hours. Additional groups received either LA (100 mg/kg) or 6-FP (14 mg/kg) 30 minutes prior to the onset of CO + noise. Cochlear function was monitored using distortion product otoacoustic emissions, and auditory thresholds were assessed using compound action potentials recorded from the round window. Histopathological evaluation of the organ of Corti provided counts of missing hair cells in each treatment group. The CO + noise-exposure group replicated previous studies in demonstrating permanent impairment of cochlear function and associated outer hair cell loss that greatly exceeded the minimal losses observed in the group treated with noise alone. Both LA and 6-FP given 30 minutes prior to the onset of CO + noise exposure reduced cochlear impairment and loss of hair cells.

Topics: Animals; Carbon Monoxide; Disease Models, Animal; Hair Cells, Auditory; Hearing Loss, Noise-Induced; Male; Pterins; Rats; Thioctic Acid

Neuroprotective effects of 6-formylpterin (6FP) on transient retinal ischemia-reperfusion injury were evaluated in rats by means of counting the number of retinal ganglion cells, measuring the thicknesses of the inner plexiform and inner nuclear layers, and by immunohistochemical detection of apoptotic cells in the retina. Sixty-one Sprague-Dawley rats (12 weeks, male, 295-330 g) were subjected to transient retinal ischemia-reperfusion by elevated intra-ocular pressure (80 mmHg for 60 min). Intraperitoneal injection of 6FP (3.8 mg/kg) was performed before or after ischemia. The retina was histologically better preserved in rats with 6FP treatment than without 6FP treatment. 6FP showed more strong neuroprotective effects when it was administered before ischemia. The number of single-stranded DNA-positive cells in the retina also decreased remarkably in rats with 6FP treatment, especially when administered before ischemia. These results suggest that 6FP protects retinal neurons from transient ischemia-reperfusion injury, at least in part by inhibiting apoptotic cell death.

Topics: Animals; Apoptosis; Disease Models, Animal; Immunohistochemistry; Injections, Intraperitoneal; Neuroprotective Agents; Pterins; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Retinal Ganglion Cells; Time Factors