Translocator Protein Modulation by 4'-Chlorodiazepam and NO Synthase Inhibition Affect Cardiac Oxidative Stress, Cardiometabolic and Inflammatory Markers in Isoprenaline-Induced Rat Myocardial Infarction

Int J Mol Sci. 2021 Mar 11;22(6):2867. doi: 10.3390/ijms22062867.

Abstract

The possible cardioprotective effects of translocator protein (TSPO) modulation with its ligand 4'-Chlorodiazepam (4'-ClDzp) in isoprenaline (ISO)-induced rat myocardial infarction (MI) were evaluated, alone or in the presence of L-NAME. Wistar albino male rats (b.w. 200-250 g, age 6-8 weeks) were divided into 4 groups (10 per group, total number N = 40), and certain substances were applied: 1. ISO 85 mg/kg b.w. (twice), 2. ISO 85 mg/kg b.w. (twice) + L-NAME 50 mg/kg b.w., 3. ISO 85 mg/kg b.w. (twice) + 4'-ClDzp 0.5 mg/kg b.w., 4. ISO 85 mg/kg b.w. (twice) + 4'-ClDzp 0.5 mg/kg b.w. + L-NAME 50 mg/kg b.w. Blood and cardiac tissue were sampled for myocardial injury and other biochemical markers, cardiac oxidative stress, and for histopathological evaluation. The reduction of serum levels of high-sensitive cardiac troponin T hs cTnT and tumor necrosis factor alpha (TNF-α), then significantly decreased levels of serum homocysteine Hcy, urea, and creatinine, and decreased levels of myocardial injury enzymes activities superoxide dismutase (SOD) and glutathione peroxidase (GPx) as well as lower grades of cardiac ischemic changes were demonstrated in ISO-induced MI treated with 4'-ClDzp. It has been detected that co-treatment with 4'-ClDzp + L-NAME changed the number of registered parameters in comparison to 4'-ClDzp group, indicating that NO (nitric oxide) should be important in the effects of 4'-ClDzp.

Keywords: 4′-CIDzp; NO synthase inhibition; myocardial infarction; rat; translocator protein.

MeSH terms

  • Animals
  • Benzodiazepinones / pharmacology*
  • Biomarkers / blood
  • Biomarkers / metabolism
  • Carrier Proteins / metabolism*
  • Enzyme Inhibitors / pharmacology
  • Glutathione Peroxidase / metabolism
  • Homocysteine / blood
  • Isoproterenol
  • Male
  • Myocardial Infarction / chemically induced
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / prevention & control*
  • Myocardium / enzymology
  • NG-Nitroarginine Methyl Ester / pharmacology*
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / metabolism
  • Oxidative Stress / drug effects*
  • Rats
  • Rats, Wistar
  • Receptors, GABA-A / metabolism*
  • Superoxide Dismutase / metabolism
  • Troponin T / blood
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Benzodiazepinones
  • Biomarkers
  • Carrier Proteins
  • Enzyme Inhibitors
  • Receptors, GABA-A
  • Troponin T
  • Tumor Necrosis Factor-alpha
  • Homocysteine
  • Tspo protein, rat
  • 4'-chlorodiazepam
  • Glutathione Peroxidase
  • Nitric Oxide Synthase
  • Superoxide Dismutase
  • Isoproterenol
  • NG-Nitroarginine Methyl Ester