# Translocator Protein Modulation by PK11195 and NO Synthase Inhibition Affect Cardiac Oxidative Stress and Cardiometabolic and Inflammatory Markers in Isoprenaline-Induced Rat Myocardial Injury

## TL;DR

This study explores how a protein called TSPO, when modulated with a drug called PK11195, affects heart injury in rats, and how nitric oxide signaling influences these effects.

## Contribution

The study reveals the complex interplay between TSPO modulation and nitric oxide signaling in acute myocardial injury, highlighting TSPO as a multifaceted therapeutic target.

## Key findings

- PK11195 treatment reduced inflammation and protected against heart injury in rats.
- TSPO modulation was linked to adverse metabolic effects like elevated fibrinogen and homocysteine.
- Nitric oxide availability is crucial for the protective effects of PK11195.

## Abstract

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 Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME), on cardiometabolic, inflammatory, oxidative stress, and histopathological parameters in an experimental model of isoprenaline-induced 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 pro-inflammatory 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.