Translocator protein (TSPO) regulates mitochondrial function, inflammation, and oxidative
stress; however, its role in acute myocardial injury (MI) remains incompletely understood.
While previous studies have examined TSPO ligands in cardiac injury, the interplay between TSPO modulation and nitric oxide (NO) signaling in AMI has not been systematically
investigated. The aim of this study was to investigate the effects of TSPO modulation by
PK11195, alone or in combination with nitric oxide synthase (NOS) inhibition by NωNitro-L-arginine methyl ester hydrochloride (L-NAME), on cardiometabolic, inflammatory,
oxidative stress, and histopathological parameters in an experimental model of isoprenalineinduced MI in rats. Male Wistar albino rats were divided into four groups: control (C);
isoprenaline + saline-treated (ISO); isoprenaline + PK11195-treated (IP); and isoprenaline
+ PK11195 + L-NAME-treated (IPLN) groups. Isoprenaline administration induced MI,
evidenced by elevated cardiac biomarkers, electrocardiographic (ECG) alterations, and
histopathological damage. PK11195 treatment significantly attenuated MI and reduced proinflammatory cytokine levels while increasing anti-inflammatory cytokine levels, indicating
protective effects. Nevertheless, TSPO modulation was associated with adverse metabolic
effects, notably elevated fibrinogen and plasma homocysteine levels. Co-administration of
L-NAME mechanistically demonstrated that NO availability is essential for PK11195 cardioprotective effects, as NOS inhibition partially abolished cardioprotection and modified oxidative stress parameters. Overall, TSPO modulation exerts complex actions in acute MI
through regulating mitochondrial function, inflammatory signaling, and NO pathways,
suggesting that TSPO is a potential, multifaceted therapeutic target.
