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Cytotoxic Effects of Intranasal Midazolam on Nasal Mucosal Tissue

Ozbay, I MD*; Kucur, C MD*; Değer, A MD; Ital, I MD; Kasim, Cayci M; Oghan, F MD*

doi: 10.1097/SCS.0000000000001965
Brief Clinical Studies

The aim of this experimental study was to investigate the cytotoxic effects of intranasal midazolam on nasal mucosal tissue in rats. Forty healthy rats were randomly divided into 5 groups. Group 1 (n = 8) was the control group, group 2 (n = 8) received intranasal saline, group 3 (n = 8) received intranasal midazolam, group 4 (n = 8) received intraperitoneal saline, and group 5 received intraperitoneal midazolam (n = 8). Midazolam and saline were administered via intraperitoneal and intranasal routes at doses of 200 μg/kg. Nasal septal mucosal stripe tissues were removed at the 6th hour. All materials were evaluated according to Ki67 and p53 staining to evaluate proliferation and apoptosis, respectively, and hemotoxylin and eosin staining was performed for histopathology evaluation. Ki67 values and inflammation in group 3 were statistically higher compared to group 1, group 2, and group 4. P53 values in group 3 were statistically higher compared to group 1. Assessment of subepithelial edema between group 3 and the other groups revealed no statistically significant differences. Assessment of cilia loss between group 3 and group 1, group 2, and group 4 revealed no statistically significant difference. The evaluation of goblet cell loss between group 3 and group 1 revealed a statistically significant difference. Intranasal midazolam had adverse effects on nasal mucosa. However, intranasal midazolam is as safe as systemic midazolam administration with respect to nasal mucosa.

*Department of ORL, Dumlupinar University, Kutahya, Turkey

Department of Pathology, Dumlupinar University, Kutahya, Turkey

Department of Anesthesiology and Reanimation, Dumlupinar University, Kutahya, Turkey

§Department of Biology, Dumlupinar University, Kutahya, Turkey.

Address correspondence and reprint requests to Isa Ozbay, Department of Otolaryngology, Faculty of Medicine, Dumlupinar University, Kutahya, Turkey; E-mail:

Received 14 February, 2015

Accepted 1 May, 2015

The abstract of manuscript was submitted to 3rd Congress of European ORL-HNS (7-11 June 2015, Prague, Czech Republic) for oral presentation.

This article was supported by Coordinator of Scientific Research and Project, Dumlupinar University.

The authors report no conflicts of interest.

© 2015 by Mutaz B. Habal, MD.