Limits...
Dose-dependent protection on cisplatin-induced ototoxicity - an electrophysiological study on the effect of three antioxidants in the Sprague-Dawley rat animal model.

Lorito G, Hatzopoulos S, Laurell G, Campbell KC, Petruccelli J, Giordano P, Kochanek K, Sliwa L, Martini A, Skarzynski H - Med. Sci. Monit. (2011)

Bottom Line: At the post-treatment follow-up no significant threshold change at 8 kHz was found in the D-Met- and NAC-treated groups.All ebselen-treated animals presented significant threshold elevations.The ebselen-treated animals presented significant threshold shifts and showed the highest threshold elevations.

View Article: PubMed Central - PubMed

Affiliation: Department of Audiology, University of Ferrara, Ferrara, Italy.

ABSTRACT

Background: Sprague-Dawley rats were used as an acute cisplatin ototoxicity model to compare the chemo-protective efficacy of 2 sulphur-containing antioxidants (D-methionine, N-L-acetylcysteine) and 1 seleno-organic compound (ebselen). Each putative chemo-protective agent was tested at 3 different dosages in order to assess the influence of dose on auditory preservation.

Material/methods: A total of 40 Sprague-Dawley albino male rats were used in the study. Animals were divided into 10 groups, 3 groups of different doses for each protective agent and a cisplatin-treated control group. The animals were weight-matched before drug exposure to ensure similar weights in all groups. Auditory function was assessed with auditory brainstem responses and distortion product otoacoustic emissions at time zero and at 96 hours post-treatment.

Results: At the post-treatment follow-up no significant threshold change at 8 kHz was found in the D-Met- and NAC-treated groups. All ebselen-treated animals presented significant threshold elevations. At 12 and 16 kHz, only the groups treated with 300, 450 mg/kg of D-Met and 475 mg/kg of NAC presented thresholds comparable to the pre-treatment ABR data. The ebselen-treated animals presented significant threshold shifts and showed the highest threshold elevations. The DPOAE data analysis showed that only the animals from the 350 mg/kg D-met group presented lack of statistical differences between the pre and post recordings.

Conclusions: Considering the outcome from the ABR and DPOAE analyses together, only the 350 mg/kg D-met group presented a complete auditory preservation against the 14 mg/kg cisplatin administered i.v. Data from ebselen pre-treated Sprague-Dawley albino male rats demonstrate that ebselen dosages up to 12 mg/kg given by i.p. administration lack auditory preservation in this species.

Show MeSH

Related in: MedlinePlus

DP-Grams from untreated animals, animals treated with cisplatin (CDDP) and cisplatin plus D-met (d-met 350). The top curve (pre) represents the DPOAE responses from all tested animals. The vertical bars indicate standard error measurements. Significant differences are marked by an asterisk. The significant differences per frequency and per protector are reported in Table 2.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3539615&req=5

f5-medscimonit-17-8-br179: DP-Grams from untreated animals, animals treated with cisplatin (CDDP) and cisplatin plus D-met (d-met 350). The top curve (pre) represents the DPOAE responses from all tested animals. The vertical bars indicate standard error measurements. Significant differences are marked by an asterisk. The significant differences per frequency and per protector are reported in Table 2.

Mentions: The DPOAE analysis showed that cisplatin causes an average negative shift in the DPOAE amplitude in the order of 20 dB in the frequency span from 6.5 to 17 kHz. Figures 5 and 6 summarize the DP-Gram information from untreated and treated animals with cisplatin and otoprotectors. Only the animals from the group treated with 350 mg/kg of D-met presented lack of statistical differences between the pre and post DPOAE recordings. All other groups showed significant alterations in DPOAE amplitude, including groups 3 and 6 (400 mg/kg D-met and 475 mg/kg NAC). The 3 ebselen-treated groups showed statistical differences at all tested frequencies, and in a number of animals it was not possible to record a post-treatment DPOAE response. The DPOAE data are also summarized in Table 2. Table 3 shows the average weight loss of the experimental animals per treatment group. The data indicate that only the 375 mg NAC treatment provides partial protection against cisplatin-induced weight loss. Animals treated by 275 mg of NAC had a borderline (P=0.058) weight loss, whereas animals included in all the remaining treatment groups showed a significant CDDP-dependant weight loss.


Dose-dependent protection on cisplatin-induced ototoxicity - an electrophysiological study on the effect of three antioxidants in the Sprague-Dawley rat animal model.

Lorito G, Hatzopoulos S, Laurell G, Campbell KC, Petruccelli J, Giordano P, Kochanek K, Sliwa L, Martini A, Skarzynski H - Med. Sci. Monit. (2011)

DP-Grams from untreated animals, animals treated with cisplatin (CDDP) and cisplatin plus D-met (d-met 350). The top curve (pre) represents the DPOAE responses from all tested animals. The vertical bars indicate standard error measurements. Significant differences are marked by an asterisk. The significant differences per frequency and per protector are reported in Table 2.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3539615&req=5

f5-medscimonit-17-8-br179: DP-Grams from untreated animals, animals treated with cisplatin (CDDP) and cisplatin plus D-met (d-met 350). The top curve (pre) represents the DPOAE responses from all tested animals. The vertical bars indicate standard error measurements. Significant differences are marked by an asterisk. The significant differences per frequency and per protector are reported in Table 2.
Mentions: The DPOAE analysis showed that cisplatin causes an average negative shift in the DPOAE amplitude in the order of 20 dB in the frequency span from 6.5 to 17 kHz. Figures 5 and 6 summarize the DP-Gram information from untreated and treated animals with cisplatin and otoprotectors. Only the animals from the group treated with 350 mg/kg of D-met presented lack of statistical differences between the pre and post DPOAE recordings. All other groups showed significant alterations in DPOAE amplitude, including groups 3 and 6 (400 mg/kg D-met and 475 mg/kg NAC). The 3 ebselen-treated groups showed statistical differences at all tested frequencies, and in a number of animals it was not possible to record a post-treatment DPOAE response. The DPOAE data are also summarized in Table 2. Table 3 shows the average weight loss of the experimental animals per treatment group. The data indicate that only the 375 mg NAC treatment provides partial protection against cisplatin-induced weight loss. Animals treated by 275 mg of NAC had a borderline (P=0.058) weight loss, whereas animals included in all the remaining treatment groups showed a significant CDDP-dependant weight loss.

Bottom Line: At the post-treatment follow-up no significant threshold change at 8 kHz was found in the D-Met- and NAC-treated groups.All ebselen-treated animals presented significant threshold elevations.The ebselen-treated animals presented significant threshold shifts and showed the highest threshold elevations.

View Article: PubMed Central - PubMed

Affiliation: Department of Audiology, University of Ferrara, Ferrara, Italy.

ABSTRACT

Background: Sprague-Dawley rats were used as an acute cisplatin ototoxicity model to compare the chemo-protective efficacy of 2 sulphur-containing antioxidants (D-methionine, N-L-acetylcysteine) and 1 seleno-organic compound (ebselen). Each putative chemo-protective agent was tested at 3 different dosages in order to assess the influence of dose on auditory preservation.

Material/methods: A total of 40 Sprague-Dawley albino male rats were used in the study. Animals were divided into 10 groups, 3 groups of different doses for each protective agent and a cisplatin-treated control group. The animals were weight-matched before drug exposure to ensure similar weights in all groups. Auditory function was assessed with auditory brainstem responses and distortion product otoacoustic emissions at time zero and at 96 hours post-treatment.

Results: At the post-treatment follow-up no significant threshold change at 8 kHz was found in the D-Met- and NAC-treated groups. All ebselen-treated animals presented significant threshold elevations. At 12 and 16 kHz, only the groups treated with 300, 450 mg/kg of D-Met and 475 mg/kg of NAC presented thresholds comparable to the pre-treatment ABR data. The ebselen-treated animals presented significant threshold shifts and showed the highest threshold elevations. The DPOAE data analysis showed that only the animals from the 350 mg/kg D-met group presented lack of statistical differences between the pre and post recordings.

Conclusions: Considering the outcome from the ABR and DPOAE analyses together, only the 350 mg/kg D-met group presented a complete auditory preservation against the 14 mg/kg cisplatin administered i.v. Data from ebselen pre-treated Sprague-Dawley albino male rats demonstrate that ebselen dosages up to 12 mg/kg given by i.p. administration lack auditory preservation in this species.

Show MeSH
Related in: MedlinePlus