Caffeic acid phenethyl ester protects the brain against hexavalent chromium toxicity by enhancing endogenous antioxidants and modulating the JAK/STAT signaling pathway.

Abstract

Hexavalent chromium [Cr(VI)] is commonly used in industry, and is a proven toxin and carcinogen. However, the information regarding its neurotoxic mechanism is not completely understood. The present study was designed to scrutinize the possible protective effects of caffeic acid phenethyl ester (CAPE), a bioactive phenolic of propolis extract, on Cr(VI)-induced brain injury in rats, with an emphasis on the JAK/STAT signaling pathway. Rats received 2mg/kgK2CrO4 and concurrently treated with 20mg/kg CAPE for 30 days. Cr(VI)-induced rats showed a significant increase in cerebral lipid peroxidation, nitric oxide and pro-inflammatory cytokines, with concomitantly declined antioxidants and acetylcholinesterase. CAPE attenuated oxidative stress and inflammation and enhanced antioxidant defenses in the cerebrum of rats. Cr(VI) significantly up-regulated JAK2, STAT3 and SOCS3, an effect that was reversed by CAPE. In conclusion, CAPE protects the brain against Cr(VI) toxicity through abrogation of oxidative stress, inflammation and down-regulation of JAK2/STAT3 signaling in a SOCS3-independent mechanism.

• Authors: Ayman M Mahmoud, Sanaa M Abd El-Twab
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 91 Pg. 303-311 (Jul 2017) ISSN: 1950-6007 [Electronic] France
• PMID: 28463793 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Chemical References

• Antioxidants
• Caffeic Acids
• Neuroprotective Agents
• RNA, Messenger
• STAT Transcription Factors
• Socs3 protein, rat
• Suppressor of Cytokine Signaling 3 Protein
• Chromium
• chromium hexavalent ion
• Nitric Oxide
• Glutathione Peroxidase
• Superoxide Dismutase
• Janus Kinases
• Acetylcholinesterase
• caffeic acid phenethyl ester
• Glutathione
• Phenylethyl Alcohol

Topics

• Acetylcholinesterase (metabolism)
• Animals
• Antioxidants (pharmacology)
• Caffeic Acids (chemistry, pharmacology)
• Cerebrum (drug effects, pathology)
• Chromium (toxicity)
• Down-Regulation (drug effects)
• Glutathione (metabolism)
• Glutathione Peroxidase (metabolism)
• Inflammation (pathology)
• Janus Kinases (metabolism)
• Lipid Peroxidation (drug effects)
• Male
• Neuroprotective Agents (pharmacology)
• Nitric Oxide (biosynthesis)
• Oxidative Stress (drug effects)
• Phenylethyl Alcohol (analogs & derivatives, chemistry, pharmacology)
• Phosphorylation (drug effects)
• RNA, Messenger (genetics, metabolism)
• Rats, Wistar
• STAT Transcription Factors (metabolism)
• Signal Transduction (drug effects)
• Superoxide Dismutase (metabolism)
• Suppressor of Cytokine Signaling 3 Protein (metabolism)