The apoptotic effect of midazolam on the salivary gland of rats and the reversal effect by pilocarpine.

To evaluate the apoptosis in parotid glands of rats treated with midazolam associated or not with pilocarpine, 60 Wistar rats were assigned to 6 groups: control groups received saline solution for 30 days (S30) and 60 days (S60) and the other groups received pilocarpine for 60 days (P60), midazolam for 30 days (M30), midazolam for 30 days and 30 days of saline (M30 + S30), and finally midazolam for 30 days and 30 days of midazolam and pilocarpine (M30 + MP30). Histological sections were subjected to the TdT-mediated dUTP-biotin nick and labeling technique. The number of positive and negative cells was quantified, calculating the apoptotic index. ANOVA at 2 criteria and Tukey's test were used. A greater apoptotic index was observed in the M30 (52.79 ± 9.01) and M30 + S30 (62.43 ± 8.52) groups when compared with the S30 (37.94 ± 5.94) and S60 (31.85 ± 9.18) groups, respectively (p < 0.05). There was no difference between M30 + MP30 (30.98 ± 6.19) and S60 (31.85 ± 9.18) groups regarding apoptotic index. Chronic administration of midazolam has been shown to increase the number of apoptotic cells in the parotid glands of rats. However, pilocarpine inhibited this effect, thus inhibiting the apoptosis.

Effects of Benzodiazepines on Acinar and Myoepithelial Cells.

BACKGROUND: Benzodiazepines (BZDs), the most commonly prescribed psychotropic drugs with anxiolytic action, may cause hyposalivation. It has been previously shown that BZDs can cause hypertrophy and decrease the acini cell number. In this study, we investigated the effects of BZDs and pilocarpine on rat parotid glands, specifically on acinar, ductal, and myoepithelial cells. METHODS: Ninety male Wistar rats were divided into nine groups. Control groups received a saline solution for 30 days (C30) and 60 days (C60), and pilocarpine (PILO) for 60 days. Experimental groups received lorazepam (L30) and midazolam (M30) for 30 days. Another group (LS60 or MS60) received lorazepam or midazolam for 30 days, respectively, and saline for additional 30 days. Finally, other groups (LP60 or MP60) received either lorazepam or midazolam for 30 days, respectively, and pilocarpine for additional 30 days. The expression of calponin in myoepithelial cells and the proliferating cell nuclear antigen (PCNA) in acinar and ductal cells were evaluated. RESULTS: Animals treated with lorazepam showed an increase in the number of positive staining cells for calponin as compared to control animals (p < 0.05). Midazolam administered with pilocarpine (MP60) induced an increase in the proliferation of acinar and ductal cells and a decrease in the positive staining cells for calponin as compared to midazolam administered with saline (MS60). CONCLUSION: We found that myoepithelial cells might be more sensitive to the effects of BZD than acinar and ductal cells in rat parotid glands.