# Evaluation of Ototoxic Effects of Cisplatin in a Rat Model: A Dose-Response Study
## 3 Results
### Morphological Changes in Renal Structures  
In the NT group, it was possible to appreciate the normal morphology of the kidney, with clearly identifiable cortical and medulla regions, normal glomeruli, intact proximal convoluted tubules (PCTs), and distal convoluted tubules (DCTs) and Henle's loop (Figure 6, NT group). In the 1-IP group, the damaged areas extend to almost all of the cortex and part of the medulla. The tissue in the areas of necrosis and damage is less compact and is evidenced by a lower hematoxylin-eosin stain (Figure 6, 1-IP group, cortex, and medulla). Damages included glomerular atrophy (Figure 6, cortical region), necrosis of the PCT epithelium with extensive infiltration of inflammatory cells (Figure 6, cortex/medulla), and the presence of hyaline casts in the DCT of the medulla (Figure 6, medulla region). In the 3-IP group, necrotic areas are less extended and restricted to the boundary between the cortex and the medulla (Figure 6, 3-IP group) compared to 1-IP rats. Dilation of the DCT in the medulla and the presence of few inflammatory cells in the DCT lumen (Figure 6, medulla region) were also observed. It should be noted that the identification of inflammatory cells was based on H&E staining, which is not definitive without specific inflammatory markers. On the contrary, although cisplatin treatment caused a significant reduction in the glomerular area compared to the NT group (17%), no significant differences were observed between the two treated groups, and no significant variations were detected among all groups in terms of glomerular density (Figure 7a,b). The study of DCT and PCT lumen \begin{table}
\begin{tabular}{c c c c} \hline  & **NT** & **1-IP** & **3-IP** \\ \hline Area & 100 \(\pm\) 22.73 & 105.2 \(\pm\) 2.73 & 105.7 \(\pm\) 349 \\ Thickness & 97 (77.6; 105) & 106 (93; 114) & 97 (91.4; 106.9) \\ Basal region & 12.8 \(\pm\) 2.0 & 15.1 \(\pm\) 5.8 & 12.7 \(\pm\) 2.4 \\ \hline \end{tabular} Stria vascularis area values are expressed in terms of mean \(\pm\) standard error of the mean, and differences were measured among groups by using one-way ANOVA (F (2, 34) = 0.4617, \(p\)-value = 0.634). Stria vascularis thickness values are expressed in terms of the median (1 st percentile; 3 rd percentile), and differences were measured among groups by using the Kruskal–Wallis test (H = 4.699, \(p\)-value = 0.095).  
\end{table} 
Table 2: Stria vascularis. Data were obtained by multiplying the ratio of neuronal nuclei to ganglia area by 10,000 for each treatment group and cochlear region. Figure 5: Hair cells count. (**a**) Number of hair cells in the three experimental groups according to the cochlear regions, respectively, the basal region (dark gray color), the medial region (light gray color), and the apical region (white color). (**b**) The percentage of hair cells present in the basal and medial regions of the cochlea in the three experimental groups was reported based on the type of hair cells. The median and quartile intervals of hair cells (HCs) reported for each group were expressed as a percentage. Kruskal–Wallis and [PERSON]’s multiple comparison tests were used to analyze differences in % of HCs among the treatment groups. NT: not-treated animals; 1-IP: animals treated with one cisplatin bolus; 3-IP: animals treated with three consecutive cisplatin doses (IHCs: inner hair cells; OHCs: outer hair cells; *: \(p\) \(<\) 0.05; *: \(p\) \(<\) 0.01; ***: \(p\) \(<\) 0.001.  
thickness revealed significant dilatation for both tubules in both CDDP treatments, with comparable results (Figure 7c,d). Figure 6: Sections of kidney stained with hematoxylin-eosin in NT group, 1-IP group, and 3-IP group, respectively. The first line shows images of the entire area from the cortex to the (bars = 200 \(\upmu\)m; magnification 100X. The following lines detail: glomeruli (*) and proximal convoluted tubules (PCTs) in the cortical region; boundary between cortex and medulla; distal convoluted tubules (DCTs) and loops of Henle in the medulla. Arrowheads indicate immunity cells.