Histomorphometric Analysis of Salivary Gland in Wistar Rats Treated Chronically With Two Benzodiazepines

Abstract

Benzodiazepines (BZDs), the most commonly prescribed psychotropic drugs with anxiolytic action, may cause hyposalivation. Therefore, this study sought to quantify the acini (N) in parotid glands of Wistar rats treated chronically with two BZDs (Lorazepam and Midazolan) and to verify the action of the pilocarpine when administered with these drugs. Ninety male Wistar rats were distributed in 9 groups according to the administration of: a) S30 - saline solution for 30 days; b) S60 - saline solution for 60 days; c) P60 - pilocarpine for 60 days; d) L30 - Lorazepam for 30 days; e) M30 - Midozolam for 30 days; f) LS60 - Lorazepam for 60 days and, after this period, 30 more days of saline solution; g) MS60 - Midazolam for 30 days and, after this period, 30 more days of saline solution; h) LP60 - Lorazepam and Pilocarpine for 60 days; i) MP60 - Midazolam and Pilocarpine for 60 days. A surgery was performed on the animals to remove the glands. After this, histological cuts were stained by hematoxylin and eosin, from which the N was quantified. The ANOVA and Games-Howell tests were used for statistical analysis. The L30 and M30 groups presented less N than did the S30 group (p<0.05). The LS60, MS60, and LP60 groups presented less N than did the S60 and P60 groups (p<0.05). No differences could be observed between the MP60 and S60 groups. The chronic administration of Midazolam and Lorazepam reduced acini, which may well have collaborated in the reduction of salivary flow previously verified. The association of Midazolam with Pilocarpine led to the reestablishment of acinar cells, which may have favored the restoration of the salivary flow formerly shown.

Effects of Benzodiazepines on Acinar and Myoepithelial Cells

“…Rinaldi et al ( 2015 ) confirmed that chronic administration of midazolam and lorazepam reduced the number of acinar cells in the parotid glands of rats, which may have contributed to the reduction of salivary flow. The association of midazolam with pilocarpine led to the reestablishment of acinar cells, which may have favored the restoration of the salivary flow, as shown above.…”

“… δ Values obtained from findings reported by Rinaldi et al ( 2015 ); SSFR (mL/min), Stimulated salivary flow rate in millimeters per minute; CV, Cell volume in square micrometers; PCNA, Proliferating Cell Nuclear Antigen; C, Antibody against calponin antigen; X, average; SD, standard deviation;p, p-value of ANOVA;Similar letter represents statistically significant difference between the groups . …”

“…In addition to calponin and PCNA variables, this study also used the average values for the stimulated salivary flow rate (SSFR) and cellular volume (CV) as determined in a study by Rinaldi et al ( 2015 ). Because the present study investigated the same sample as was performed previously (Rinaldi et al, 2015 ), the SSFR and CV findings were compared to the immunohistochemical staining results for calponin and PCNA.…”

“…The level of significance for all statistical tests was set at 5% ( p < 0.05). The analyzed variables were calponin and PNCA, which were compared to the CV and SSFR variables (Rinaldi et al, 2015 ). See more details in Supplementary Materials about statistical analysis.…”