# From Redox Imbalance to Tissue Injury: Insights Into Antidepressant Drug Amitriptyline Effects on Salivary Glands

**Authors:** Cristian dos Santos Pereira, Deiweson Souza‐Monteiro, Yago Gecy de Sousa Né, Jorddy Neves da Cruz, Vinicius Ruan Neves dos Santos, Everton Luiz Pompeu Varela, Sandro Percário, Leonardo Oliveira Bittencourt, Antonio Hernandes Chaves‐Neto, Rafael Rodrigues Lima

PMC · DOI: 10.1002/cbf.70189 · Cell Biochemistry and Function · 2026-03-01

## TL;DR

This study shows that amitriptyline, an antidepressant, can harm rat salivary glands by causing oxidative stress and changing saliva composition.

## Contribution

The study reveals new insights into how amitriptyline affects salivary glands through oxidative imbalance and morphological changes.

## Key findings

- Amitriptyline increased total protein in saliva but decreased amylase activity.
- The drug caused oxidative stress in salivary glands, indicated by reduced antioxidant capacity and increased lipid peroxidation.
- Morphometric analysis showed increased stromal area and decreased ductal and acinar areas in salivary glands.

## Abstract

This study aimed to investigate the effects of amitriptyline administration on the salivary glands and saliva of rats. Twenty‐eight male Wistar rats (60 days old) were divided into two groups (n = 14 per group): control and amitriptyline‐treated (10 mg/kg/day for 30 days). After the treatment period, saliva samples induced by pilocarpine were collected to analyze total protein concentration, amylase activity, and antioxidant capacity, while salivary glands were harvested for assessments of oxidative stress markers and morphological changes. Amitriptyline increased total protein and decreased amylase activity in saliva, with no change in the Trolox‐equivalent antioxidant capacity (TEAC). The drug triggered oxidative stress in both glands by the decrease in TEAC concentration and increased lipid peroxidation. Morphometric analysis showed that amitriptyline increased the total area of stroma and decreased the ductal area in both glands. In the submandibular gland, acinar area was reduced as well. These findings suggest that amitriptyline‐salivary gland dysfunction is associated with oxidative imbalance, morphometric, and alterations in saliva composition, contributing to a broader understanding of amitriptyline's adverse effects.

The study aimed to evaluate the effects of chronic amitriptyline administration on the salivary glands, given the doubts about its biochemical, morphological, and functional repercussions. Exposure to the drug reduced amylase activity, modulated salivary protein content, and induced oxidative stress in the submandibular and parotid glands, which also showed significant morphological changes. These findings highlight the physiological and histological effects of amitriptyline, contributing to the understanding of its adverse mechanisms. In addition, they provide a basis for future research on the systemic effects of the drug, the development of therapeutic strategies to reduce its harm, and the safer use of tricyclic antidepressants in clinical practice.

## Linked entities

- **Chemicals:** amitriptyline (PubChem CID 2160), pilocarpine (PubChem CID 4819), Trolox (PubChem CID 40634)

## Full-text entities

- **Genes:** CYCS (cytochrome c, somatic) [NCBI Gene 54205] {aka CYC, HCS, THC4}, Mapk8 (mitogen-activated protein kinase 8) [NCBI Gene 116554] {aka JNK}, Ddit3 (DNA-damage inducible transcript 3) [NCBI Gene 29467] {aka CHOP, CHOP-10, Chop10, Gadd153, RM4}, Atf6 (activating transcription factor 6) [NCBI Gene 304962]
- **Diseases:** confusion (MESH:D003221), Tachycardia (MESH:D013610), affective disorders (MESH:D019964), neuroendocrine dysfunction (MESH:D018358), Mitochondrial dysfunction (MESH:D028361), inflammation (MESH:D007249), atrophy (MESH:D001284), salivary hypofunction (MESH:D000309), psychiatric (MESH:D001523), constipation (MESH:D003248), TEAC (MESH:D064386), chronic pain (MESH:D059350), dry mouth (MESH:D014987), migraine (MESH:D008881), cytotoxic (MESH:D064420), diabetic neuropathy (MESH:D003929), fibromyalgia (MESH:D005356), coagulation (MESH:D001778)
- **Chemicals:** TBA (MESH:C029684), venlafaxine (MESH:D000069470), water (MESH:D014867), ethanol (MESH:D000431), 5,5-dithiobis-2-nitrobenzoic acid (MESH:D004228), HCl (MESH:D006851), noradrenaline (MESH:D009638), oxygen (MESH:D010100), phosphate (MESH:D010710), NaCl (MESH:D012965), Trolox (MESH:C010643), paraffin (MESH:D010232), xylazine hydrochloride (MESH:D014991), MDA (MESH:D015104), nitrogen (MESH:D009584), xylene (MESH:D014992), Amitriptyline (MESH:D000639), lipid (MESH:D008055), 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid (MESH:C002502), Glutathione (MESH:D005978), ketamine hydrochloride (MESH:D007649), isoproterenol (MESH:D007545), fluoxetine (MESH:D005473), benznidazole (MESH:C009999), calcium (MESH:D002118), ROS (MESH:D017382), peroxyl radical (MESH:C049375), formaldehyde (MESH:D005557), serotonin (MESH:D012701), TBARS (MESH:D017392), heparin (MESH:D006493), eosin (MESH:D004801), n-butyl alcohol (MESH:D020001), pilocarpine (MESH:D010862), Hematoxylin (MESH:D006416), sibutramine (MESH:C058254), Coomassie brilliant blue dye (-), K2S2O8 (MESH:C009007), nitrobenzoic acid (MESH:D009579), malondialdehyde (MESH:D008315), trichloroacetic acid (MESH:D014238)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116]

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12949951/full.md

## References

46 references — full list in the complete paper: https://tomesphere.com/paper/PMC12949951/full.md

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Source: https://tomesphere.com/paper/PMC12949951