Ferric-Induced Pancreatic Injury Involves Exacerbation of Cholinergic and Proteolytic Activities, and Dysregulation of Metabolic Pathways: Protective Effect of Caffeic Acid
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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.
KeywordsAntioxidant Caffeic acid Functional chemistry Metabolomics
Fourier transform infrared
Liquid chromatography-mass spectroscopy
Type 1 diabetes
Type 2 diabetes
Kyoto Encyclopedia of Genes and Genomes
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.
Compliance with Ethical Standards
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).
Conflict of Interest
The authors declare that they have no conflict of interest.
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