3-Aminobenzamide protects against cerebral artery injury and inflammation in rats with intracranial aneurysms

Pharmazie. 2019 Mar 1;74(3):142-146. doi: 10.1691/ph.2019.8911.

Abstract

This study aimed to investigate the treatment effects and molecular mechanism of 3-aminobenzamide (3-AB) on intracranial aneurysms (IA). The IA model was established in male Sprague-Dawley (SD) rats and sham group was set up without ligation. The rats were intraperitoneally injected with normal saline in sham and model control groups and 10 mg/kg, 20 mg/kg and 40 mg/kg 3-AB for low, middle and high 3-AB groups for 3 months, respectively. The rates in and blood pressures of caudal artery were measured and anterior cerebral artery and olfactory artery were stained with hematoxylin and eosin (HE) for morphology observation. Besides, the effects of 3-AB on inflammatory cells, macrophages, neutrophils and T cells, were evaluated using immunohistochemistry. Gene expressions of TNF-α, MMP-9, MMP-2, iNOS, TLR4, PARP-1 and p65 were measured using qRT-PCR and the protein levels of TLR4, PARP-1 and p-p65 were evaluated using western blotting. Blood pressures of rats in 3-AB treatment groups were decreased in a dose-dependent manner. The damage of cerebral artery wall was alleviated and the inflammatory cells (macrophages, neutrophils and T cells) were reduced to some extent in 3-AB high-dose groups. The gene expression of TNF-α, MMP-9, MMP-2, iNOS, TLR4, PARP-1 and p65, as well as the protein expression of TLR4, PARP-1 and p-p65 in 3-AB treatment groups were decreased in a dose-dependent manner (P < 0.01).3-AB exhibited therapeutic effects on IA through inhibiting the secretions of inflammatory cytokines and MMPs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • Arterial Pressure
  • Benzamides / pharmacology*
  • Cerebral Arterial Diseases / drug therapy*
  • Cerebral Arterial Diseases / metabolism
  • Cerebral Arterial Diseases / pathology
  • Cerebral Arterial Diseases / prevention & control
  • Inflammation / drug therapy
  • Inflammation / prevention & control
  • Intracranial Aneurysm / drug therapy*
  • Intracranial Aneurysm / metabolism
  • Intracranial Aneurysm / pathology
  • Male
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • NF-kappa B / metabolism
  • Neoplasm Proteins / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Nucleocytoplasmic Transport Proteins / metabolism
  • Poly (ADP-Ribose) Polymerase-1 / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction
  • Toll-Like Receptor 4 / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antigens, CD
  • Benzamides
  • NF-kappa B
  • Neoplasm Proteins
  • Nucleocytoplasmic Transport Proteins
  • Tlr4 protein, rat
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor-alpha
  • p65 oncofetal mRNA transport protein, rat
  • 3-aminobenzamide
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat
  • Parp1 protein, rat
  • Poly (ADP-Ribose) Polymerase-1
  • Matrix Metalloproteinase 2
  • Mmp2 protein, rat
  • Matrix Metalloproteinase 9
  • Mmp9 protein, rat