Effects of Citalopram and Ticagrelor on Reserpine-Associated Myocardial Alterations: Oxidative/Nitrosative Status, Protein Immunoreactivity, and Histopathology

Abstract

Background/Objectives: Reserpine depletes vesicular monoamine stores and can affect both monoaminergic neurotransmission and cardiovascular physiology. This study investigated the effects of citalopram and ticagrelor on myocardial oxidative/nitrosative status, cardiac injury biomarkers, histopathological alterations, and NF-κB/Nrf2- and apoptosis-related protein immunoreactivity in reserpine-treated rats. Methods: Forty-eight adult male Wistar albino rats were randomly assigned to six groups (n = 8/group): sham control (SH), reserpine (RES), ticagrelor (TIC), citalopram (CIT), reserpine + ticagrelor (RES + TIC), and reserpine + citalopram (RES + CIT). Reserpine (0.2 mg/kg/day, intraperitoneally) was administered for 14 days, while ticagrelor (30 mg/kg/day) and citalopram (10 mg/kg/day) were administered by oral gavage from days 5 to 14. Cardiac MDA, NOx, and GSH; serum CK-MB and cTnT; myocardial histopathology; and NF-κB, Nrf2, Bax, Bcl-2, and cleaved caspase-3 immunoreactivity were evaluated. Results: Reserpine increased cardiac MDA and NOx levels and decreased GSH levels compared with the SH group. Ticagrelor significantly reduced MDA levels, whereas citalopram did not. Both treatments significantly reduced NOx levels and increased GSH levels compared with the RES group. Reserpine increased serum CK-MB and cTnT levels compared with the SH group. Both citalopram and ticagrelor significantly reduced CK-MB levels relative to the RES group. In contrast, a significant reduction in cTnT was observed only in the RES + TIC group; however, cTnT levels in this group remained significantly higher than those in the SH group. Histopathological assessment revealed that both treatments significantly reduced interstitial edema and inflammatory cell infiltration, but not cardiomyocyte degeneration or vascular congestion. Both treatments significantly reduced NF-κB, Bax, and cleaved caspase-3 immunoreactivity compared with the RES group. Nrf2 immunoreactivity was significantly increased only in the RES + CIT group, whereas both treatments significantly increased Bcl-2 immunoreactivity. Conclusions: Reserpine exposure was associated with myocardial oxidative/nitrosative imbalance, increased circulating cardiac injury biomarkers, histopathological alterations, and changes in inflammatory, antioxidant, and apoptosis-associated protein immunoreactivity. Both citalopram and ticagrelor reduced CK-MB levels, whereas a significant reduction in cTnT was observed only with ticagrelor, and cTnT remained elevated relative to the sham control group. Treatment-associated responses also differed for MDA and Nrf2 immunoreactivity. These findings indicate that the two treatments were associated with distinct response patterns across the measured outcomes and do not establish equivalent effects on all myocardial injury markers or demonstrate the underlying mechanisms.

The authors' abstract, as published at the source. Biomedicines, 2026 · DOI ↗