β-Caryophyllene may attenuate hyperoxaluria-induced kidney dysfunction in rats by regulating stress marker KIM-1/MCP-1 and NF-κB signaling pathway

J Biochem Mol Toxicol. 2021 Nov;35(11):e22891. doi: 10.1002/jbt.22891. Epub 2021 Aug 31.

Abstract

β-Caryophyllene (BCP), a bicyclic sesquiterpene, has proved to exhibit antioxidant and anti-inflammatory activities. The present study is carried out to investigate BCP impact on hyperoxaluria-induced kidney dysfunction in male Wistar rats. The animals were categorized into four groups, namely, Group I, control rats; Group II, ethylene glycol (inducer); Group III, inducer + BCP (100 µM/kg bw); Group IV, BCP alone. After the treatment period, the rate of creatinine clearance and the concentration of urea in urine and serum were assessed. Histopathology reports were conducted to study renal and liver tissues, while the reverse transcription-polymerase chain reaction studies were carried out for messenger RNA expression of inflammatory (nuclear factor kappa B) and endoplasmic reticulum (ER) stress (kidney dysfunction molecule-1, monocyte chemoattractant protein-1, glucose binding protein 78, CHOP, activating factor 4, and X-box binding protein-1) markers as well as antioxidant activity for the hyperoxaluric rats. Western blot was performed to investigate the level of protein expression by the treatment group on apoptotic (Bcl-2, Bax, caspase-3, and caspase-9) proteins. The results show BCP to possess a renoprotective effect under hyperoxaluric conditions by decreasing the level of the inflammatory and ER stress markers and restoring the enzymes' antioxidant activities. The histology reports depicted the satisfactory morphology of glomerulus in diseased rats. Furthermore, the results of Western blot suggested that BCP may possess inhibitory action on apoptosis by affecting the mitochondrial-dependent apoptotic pathway. Therefore, BCP can be considered as a potential candidate for the therapy of hyperoxaluric-induced kidney complications.

Keywords: ER/NF-κB signaling; apoptosis; hyperoxaluria; kidney injury; β-caryophyllene.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Biomarkers / metabolism
  • Cell Adhesion Molecules / metabolism*
  • Chemokine CCL2 / metabolism*
  • Endoplasmic Reticulum Stress / drug effects*
  • Hyperoxaluria / complications*
  • Kidney Diseases / etiology
  • Kidney Diseases / prevention & control*
  • Male
  • NF-kappa B / metabolism*
  • Polycyclic Sesquiterpenes / pharmacology*
  • Rats
  • Rats, Wistar

Substances

  • Biomarkers
  • Ccl2 protein, rat
  • Cell Adhesion Molecules
  • Chemokine CCL2
  • Havcr1protein, rat
  • NF-kappa B
  • Polycyclic Sesquiterpenes
  • caryophyllene