1. Lorazepam induces acinar cells apoptosis of rat parotid glands
- Author
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Sérgio Aparecido Ignácio, Mariana Rinaldi, Ana Maria Trindade Grégio Hardy, Yusuf S. Althobaiti, Silvana da Silva Sapelli, Edvaldo Antonio Ribeiro Rosa, Patrícia Vida Cassi Bettega, Aline Cristina Batista Rodrigues Johann, and Luciana Reis Azevedo Alanis
- Subjects
medicine.medical_specialty ,medicine.drug_class ,lcsh:Medicine ,Physical dependence ,Apoptosis ,Anxiety ,Salivary glands ,Lorazepam ,030207 dermatology & venereal diseases ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,General Dentistry ,Depression (differential diagnoses) ,TUNEL assay ,business.industry ,Depression ,lcsh:R ,Muscle relaxant ,Acinar cells ,030206 dentistry ,lcsh:RK1-715 ,Endocrinology ,lcsh:Dentistry ,Midazolam ,Original Article ,medicine.symptom ,business ,medicine.drug - Abstract
The prevalence of insomnia, depression and anxiety have recently been increasing (Kessler et al., 2005) with approximately 18.4% of the Brazilian population having experienced depression at least once during their lifetimes. These data characterize Brazil as the developing country with the largest number of people suffering from this disease (WHO, 2018). Depression is commonly accompanied by anxiety disorders and chronic psychiatric conditions with an estimated prevalence of approximately 29% (Kessler et al., 2005), which results in functional impairment that is associated with significant social costs. Treatment of these conditions includes psychological therapy and antidepressants. These drugs, such as benzodiazepines (BZDs), have been widely studied since the 1960s (Llorente et al., 2000) (WHO, 2018). BZDs are used by 9–25% of the elderly population aged 65 years of age and over, mainly among women (15–21.7% in Brazil, 9.9% in the United States, 24% in Canada and 25% in Sweden) (Jorm et al., 2000, Alvarenga et al., 2008, Johnell and Fastbom, 2009, Leggett et al., 2015). BZDs can be divided into two categories, anxiolytics and hypnotics, and can be used as anticonvulsants due to their muscle relaxant effects (De Almeida et al., 2008). As with all central-acting drugs, BZDs have side effects, such as decreased psychomotor activity, memory loss, physical dependence on long-term treatments, (Longo et al., 2000, Uzun et al., 2010) and hyposalivation and/or xerostomia, which is one of the main adverse effects described in the literature (Guggenheimer and Moore, 2003, Lambrecht et al., 2013, Raghavan et al., 2014). BZDs are among the drugs with the highest rates of complaints by patients in dental offices (Smith and Burtner, 1994) where these drugs are prescribed to reduce anxiety related to dental treatments of non-cooperative patients (Zaclikevis et al., 2009). Among the licensed BZDs, Lorazepam is one of the most widely used drugs for both insomnia and anxiety (Amato et al., 2010), particularly among elderly individuals with anxiety disorders and related conditions (Pomara et al., 2015). Previous studies, by our research group, demonstrated the damage Lorazepam and midazolam, another BDZ commonly prescribed for anxiety, caused to the acinar cells of parotid glands (Rinaldi et al., 2015, Mattioli et al., 2016, Rinaldi et al., 2018). We observed that the chronic use of BZDs significantly decreased the number and proliferation of acinar cells, reduced salivary flow and increased cell volume. In light of this, we hypothesize that the reduction in the number of acinar cells caused by Lorazepam in the salivary glands is possibly due to an apoptotic effect on these cells of the parotid glands of rats caused by the chronic use of this drug. Apoptosis plays a fundamental role in the elimination of unwanted, damaged or infected cells in multicellular organisms and serves as an important biological process in cellular development, differentiation and proliferation (So et al., 2016). The terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick end-labeling (TUNEL) (Tilly, 1996) technique is the gold standard test employed to detect apoptotic cells (Burattini et al., 2009, Heisler-Taylor et al., 2018). Because of the its wide-spread use of TUNEL, there is no need to use another technique to detect apoptotic cells. The literature lacks studies demonstrating Lorazepam-induced apoptosis in acinar cells. The aim of this study was to evaluate the apoptotic action of a BZD on the acinar cells of the parotid glands of rats by quantification of the number of apoptotic cell nuclei (NCA), the number of acinar cells (N) and the immunoexpression of nuclear proliferation cell proliferation (PCNA) protein.
- Published
- 2019