Table 1.
Distribution of Guinea pigs into various study groups.
Fig 1.
Diagram showing the lead shield that was used in order to protect the sedated guinea pigs. A 4x¾ “opening was drilled, so that the ear/auricle region of the guinea was exposed to radiation. Guinea pigs were irradiated with a Cs-137 irradiator. Sedated guinea pigs were placed on an elevated stage at the second position of the irradiator, behind the lead shield.
Fig 2.
Auditory brainstem response (ABR) thresholds of irradiated adult guinea pigs treated by intra-peritoneal or intra-tympanic injection of PrC-210.
(A) Total average thresholds at day 0, week 1 and week 2. Radiation: animals received 3000 cGy in each ear. Non-treated animals (red bars), animals treated with intra-peritoneal injection of PrC-210 (blue bars), animals treated with intra-tympanic injection of PrC-210 (yellow bars). (B) Hearing thresholds shift for the left and right ears of irradiated adult guinea pigs not treated with PrC-210 (Red) and treated by intra-peritoneal injection of PrC-210 (Blue). Total average hearing loss in dB at week 1 (light blue and light red bars) and week 2 (dark blue and dark red bars). (C) ABR pure tone thresholds of irradiated adult guinea pigs treated by an intra-peritoneal or intra-tympanic injection of PrC-210. Average pure tone thresholds at day 0, week 1 and week 2 measured at 8kHz, 16kHz and 32kHz. Radiation (Rad): animals received 3000 cGy in each ear. IP: intra-peritoneal injection of PrC-210 (blue triangles), IT: intra-tympanic injection of PrC-210 (inverted yellow triangles). Non-treated animals are indicated with red squares. Decibels (dB), *, p< = 0.05; **, p< = 0.01; ***, p< = 0.001, n.s., non significant.
Fig 3.
Cochlear sensory hair cell death in irradiated adult guinea pigs treated by an intra-peritoneal injection of PrC-210.
(A) Cochleae from irradiated adult guinea pigs that were treated by an intra-peritoneal (IP) injection of PrC-210 were dissected at week 2. Cochleae were immunostained with Myosin VIIa antibody (Green), a hair cell marker and phalloidin (Red, Grey scale), an actin marker. Scale bar = 100 μm. Dead hair cells are labeled with a star (*) (B) The dead sensory hair cells were quantified and compared to the control group. n.s., non significant.
Fig 4.
The aminothiol PrC-210 prevents the inflammation and the degeneration of the spiral ganglion induced by the radiation.
Hematoxylin and Eosin staining of paraffin section of guinea pig cochleae treated by intra-peritoneal or intratympanic injection of PrC-210 before receiving a 3000 cGy radiation dose. Guinea pig cochleae from radiation only and PrC-210 IP groups were harvest one or two weeks after being irradiated and compared to a non-irradiated animal. Arrowheads indicate the sensory hair cells in the organ of Corti. Arrows indicate the inflammation spots in the degenerative spiral ganglion neurons. Scale bar: 100μm.
Fig 5.
The aminothiol PrC-210 prevents the inflammation and the degeneration of the apical part of the spiral ganglion induced by the radiation.
Hematoxylin and Eosin staining of paraffin section of guinea pig cochleae untreated and treated by intra-peritoneal injection of PrC-210 before receiving a 3000 cGy radiation dose. Guinea pig cochleae from radiation only and PrC-210 IP groups were harvest at two weeks after being irradiated. Arrowheads indicate the sensory hair cells in the organ of Corti. Scale bar: 100μm.