# Evaluation of Ototoxic Effects of Cisplatin in a Rat Model: A Dose-Response Study
## 3 Results
### Morphological Damage to Cochlear Structures  
Upon examining the histological sections stained with hematoxylin-eosin, it was evident that the organ of Corti (ODC) of the NT group present in the three regions of the cochlea was well preserved: the three rows of outer hair cells (OHCs) and the row of inner hair cells (IHCs) have been clearly detected (Figure 4, NT group). In both groups, 1-IP and 3-IP, hair cells were lost in the middle and basal regions of the ODC, while in the apical region results appeared similar to the NT group (Figure 4). Furthermore, it appeared that the cisplatin treatments have had a greater impact on OHCs than IHCs (Figure 4, medial and basal regions).  
The cell count results have confirmed that cisplatin treatment causes, compared to the NT group, a highly significant reduction (\(p<0.001\)) in the number of cells present in the middle cochlear region (the average number of cells decreased by 36.46% for 1-IP and 4.85% for 3-IP) and an even greater and significant reduction in the basal region (68.32% for 1-IP and 25.65% for 3-IP) (Figure 5a). It can be concluded that CDDP injections, single or repeated, can cause cell damage, mainly at the base of the cochlea (\(p<0.001\)), without  
Figure 3: For each treatment group, weight loss from day 1 to 5 (**a**) and ABR threshold shifts (TS) (**b**) were reported according to the frequency range. The mean and standard deviation of the weight change reported for each group were expressed as percentages. One-way analysis of variance (ANOVA) and [PERSON]’s multiple comparison test were used to analyze differences in weight loss among groups. The median and quartile intervals of TS reported for each group according to the frequency ranges were expressed in decibels (dB SPL). Kruskal–Wallis and Dunn multiple comparison tests were used to analyze differences in ABR TS between treatment groups. NT: control group; 1-IP: group with one cisplatin bolus (14 mg/kg); 3-IP: group with three consecutive doses of cisplatin (4.6 mg/kg); *** = \(p\)-value \(<0.001\).  
significant differences between the two treatment methods (Figure 5a). In detail, it has been confirmed that OHCs were the cells that were more affected by cisplatin treatment, especially in the basal region of the cochlea. Again, the 1-IP group had significantly fewer OHCs (\(p<0.001\)) than the 3-IP group in the medial and basal regions (Figure 5b). Despite the significant damages (\(p<0.01\)) detected in the basal region of the cochlea, the IHC count did not show significant differences between the two cisplatin treatments (Figure 5b).  
The investigation of neuronal density and the area and thickness of the stria vascularis did not show significant differences among the three experimental groups (Tables 1 and 2).  
\begin{table}
\begin{tabular}{c c c c} \hline  & **NT** & **1-IP** & **3-IP** \\ \hline Apical region & 19.3 \(\pm\) 4.1 & 16.4 \(\pm\) 5.5 & 18.8 \(\pm\) 4.0 \\ Medial region & 17.7 \(\pm\) 3.3 & 18.7 \(\pm\) 2.1 & 17.8 \(\pm\) 2.8 \\ Basal region & 12.8 \(\pm\) 2.0 & 15.1 \(\pm\) 5.8 & 12.7 \(\pm\) 2.4 \\ \hline \end{tabular} Data are expressed in terms of mean \(\pm\) standard deviation. No differences on neuronal density were detected among groups by using one-way ANOVA and [PERSON]’s multiple comparison test.  
\end{table}
Table 1: Neuronal density. Data were obtained by multiplying the ratio of neuronal nuclei to ganglia area by 10,000 for each treatment group and cochlear region.  
Figure 4: Histological investigation of hair cell damage. Sections of the organ of Corti stained with hematoxylin-eosin in NT group, 1-IP group, and 3-IP group, respectively, at the apical, medial, and basal region of the cochlea. Black arrowheads indicate outer hair cells (OHCs), and clear arrowheads indicate inner hair cells (IHCs). Bar = 50 μm. Magnification 200X.