L-carnitine protects cardiac damage by reducing oxidative stress and inflammatory response via inhibition of tumor necrosis factor-alpha and interleukin-1beta against isoproterenol-induced myocardial infarction

Biomed Pharmacother. 2021 Nov:143:112139. doi: 10.1016/j.biopha.2021.112139. Epub 2021 Sep 7.

Abstract

Brief introduction: Myocardial infarction (MI) is a common manifestation of certain cardiac diseases where oxidative stress and fibrosis aggravate the condition markedly.

Main objective of the study: Investigation of L-carnitine's cardioprotective roles and mechanism of action in a rat model of MI.

Methods: To develop a MI animal model, Isoproterenol (ISO) was administered in male Long Evans rats where animals were divided into five groups (six rats/group). The oxidative stress and antioxidant enzyme activities were determined by different biochemical tests. The real-time PCR was performed to determine the expression of TNF-α and Il-1β. Histopathological observations by hematoxylin-eosin and Masson trichrome were made to observe the tissue damage and fibrosis in heart and kidney.

Significant findings from the study: The ISO-treated rats showed increased levels of troponin I and lipid peroxidation and lower antioxidant enzyme activity in heart and kidney tissues. The levels of TNF-α and IL-1β were also increased in ISO-rats. Co-administration of L-carnitine with ISO reversed all these parameters. The elevated levels of uric acid and creatinine kinase and ALP, AST and ALT activities in ISO-rats were also significantly reduced by L-carnitine administration. L-carnitine markedly decreased the infiltration of inflammatory cells and improved the tissue architecture in heart and kidney. Control animals did not show any appreciable response upon L-carnitine administration.

Relevant contribution to knowledge: These results suggest that L-carnitine plays a defensive role against cardiac and renal damage in ISO-treated MI rat model via suppressing oxidative stress and increasing antioxidant enzyme functions through inhibition of TNF-α and IL-1β.

Keywords: Cardiac fibrosis; Inflammation; Isoproterenol; L-carnitine; Oxidative stress.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Antioxidants / pharmacology*
  • Carnitine / pharmacology*
  • Disease Models, Animal
  • Fibrosis
  • Inflammation Mediators / metabolism*
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism*
  • Isoproterenol
  • Kidney / drug effects
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney Diseases / metabolism
  • Kidney Diseases / pathology
  • Kidney Diseases / prevention & control
  • Lipid Peroxidation
  • Male
  • Myocardial Infarction / chemically induced
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / pathology
  • Myocytes, Cardiac / drug effects*
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / pathology
  • Oxidative Stress / drug effects*
  • Rats
  • Rats, Long-Evans
  • Signal Transduction
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • Anti-Inflammatory Agents
  • Antioxidants
  • IL1B protein, rat
  • Inflammation Mediators
  • Interleukin-1beta
  • Tumor Necrosis Factor-alpha
  • Isoproterenol
  • Carnitine