Ferric-Induced Pancreatic Injury Involves Exacerbation of Cholinergic and Proteolytic Activities, and Dysregulation of Metabolic Pathways: Protective Effect of Caffeic Acid

Abstract

The protective effect of caffeic acid on ferric-induced pancreatic injury was investigated using ex vivo and in silico models. Incubation of pancreatic tissues with Fe2+ led to significant depleted levels of glutathione (GSH) and SOD and catalase activities, with concomitant elevated levels of malondialdehyde (MDA) and nitric oxide (NO) and acetylcholinesterase and α-chymotrypsin activities. Treatment with caffeic acid led to significant reversion of these levels and activities. Molecular docking revealed a higher binding affinity of caffeic acid with acetylcholinesterase via hydrogen bonding, Pi-Pi stacking, and Van der Waals interactions. FTIR spectroscopy of pancreatic metabolite revealed little or no effect by caffeic acid on functional groups in ferric-induced injured pancreas. The LC-MS analysis of the metabolites revealed Fe2+ caused a 20% depletion of the normal metabolites, with concomitant generation of glyceraldehyde and 3,4-dihydroxymandelaldehyde. Treatment with caffeic acid led to the restoration of TG(22:4(7Z,10Z,13Z,16Z)/24:0/22:5(7Z,10Z,13Z,16Z,19Z)) and dTDP-d-glucose, while depleting glyceraldehyde as well as activating gluconeogenesis. These results indicate the ability of caffeic acid to protect against ferric toxicity by exacerbating antioxidative activities, with concomitant inhibition of MDA and NO levels while deactivating metabolic pathways linked to oxidative stress.

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Abbreviations

GSH:

Reduced glutathione

SOD:

Superoxide dismutase

MDA:

Malondialdehyde

NO:

Nitric oxide

FTIR:

Fourier transform infrared

LC-MS:

Liquid chromatography-mass spectroscopy

FeSO4 :

Iron(II) sulfate

DM:

Diabetes mellitus

T1D:

Type 1 diabetes

T2D:

Type 2 diabetes

NaCl:

Sodium chloride

KEGG:

Kyoto Encyclopedia of Genes and Genomes

O2•− :

Superoxide anion

OOH:

Perhydroxyl radical

ONOO :

Peroxynitrite

H2O2 :

Hydrogen peroxide

•OH:

Hydroxyl radicals

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Funding

This work was supported by funding from the Research Office, University of KwaZulu-Natal, Durban, and the National Research Foundation-the World Academy of Science (NRF-TWAS), Pretoria, South Africa.

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Correspondence to Md. Shahidul Islam.

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The study was carried out in accordance with the approved guidelines of the Animal Ethics Committee of the University of KwaZulu-Natal, Durban, South Africa (protocol approval number: AREC/020/017D).

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Salau, V.F., Erukainure, O.L., Ibeji, C.U. et al. Ferric-Induced Pancreatic Injury Involves Exacerbation of Cholinergic and Proteolytic Activities, and Dysregulation of Metabolic Pathways: Protective Effect of Caffeic Acid. Biol Trace Elem Res 196, 517–527 (2020). https://doi.org/10.1007/s12011-019-01937-7

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Keywords

  • Antioxidant
  • Caffeic acid
  • Functional chemistry
  • Metabolomics