Low-dose and repeated exposure to fluoxetine leads to eryptosis and hematological disorder in Wistar rats

Fluoxetine is an antidepressant that has multiple mechanisms of action and belongs to the group of selective serotonin reuptake inhibitors. The drug has been used for the management of severe mental depression and clinical trials for other indications, including obsessive–compulsive disorder and a wide profile of related disorders. Twenty male Wistar rats were treated with two different doses of fluoxetine: 1 mg/mL (lower dose, Fluox L) and 3 mg/mL (higher dose, Fluox H) for 1 week. After the treatment, the researcher analyzes hematological and behavioral changes. A lower dose causes a decrease in erythrocyte count (RBC) and an increase in hemoglobin (HB), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC). The high dose led to an increase in RBC and a decrease in HB, mean cell volume (MCV), MCH, and MCHC. Hematological changes indicate the development of eryptosis and possible anemia. Variations in leukocyte indicators, such as a significant decrease in leukocyte counts (WBC), lymphocytes, segmented neutrophils, and an increase in the number of monocytes, indicate altered immune response, the occurrence of neutropenia, and severe monocytosis. Behavioral patterns such as depression, disorientation, and aggressiveness are more frequent at high doses. The presence of hyperglycemia indicates the development of a stress reaction. Treatment with a lower dose of fluoxetine can cause hematological disorders in case of long-term use of the drug, and a high dose of the drug can cause acute hematological changes.