Indole-3-propionic acid mitigates chlorpyrifos-mediated neurotoxicity by modulating cholinergic and redox-regulatory systems, inflammatory stress, apoptotic responses and DNA damage in rats

• Published in: Environmental toxicology and pharmacology Vol. 89; p. 103786
• Main Authors: Owumi, Solomon E., Adedara, Isaac A., Oyelere, Adegboyega K.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.01.2022; Elsevier Science Ltd
• Subjects: 8-hydroxy-2′-deoxyguanosine; Acetylcholinesterase; Animal tissues; Animals; Antioxidants; Apoptosis; Apoptosis - drug effects; Behavior, Animal - drug effects; Body weight; Caspase-3; Cerebellum; Cerebrum; Chlorpyrifos; Chlorpyrifos - administration & dosage; Chlorpyrifos - toxicity; Cholinergics; Cytokines; Damage; Deoxyguanosine; Deoxyribonucleic acid; DNA; DNA damage; DNA Damage - drug effects; Exploratory behavior; Indole-3-propionic acid; Indoles - administration & dosage; Indoles - pharmacology; Inflammation; Inflammation - drug therapy; Insecticides - toxicity; Interleukin 10; Male; Neuromodulation; Neuroprotection; Neuroprotective Agents - pharmacology; Neurotoxicity; Oxidation-Reduction - drug effects; Pesticides; Propionates - administration & dosage; Propionates - pharmacology; Propionic acid; Rats; Rats, Wistar; Redox-regulatory systems; Reductases; Scientific visualization; Stress; Thioredoxin; Chlorpyrifos; Indole-3-propionic acid; Redox-regulatory systems; 8-hydroxy-2′-deoxyguanosine; Acetylcholinesterase
• ISSN: 1382-6689; 1872-7077
• DOI: 10.1016/j.etap.2021.103786

This study probed the neuroprotective influence of indole-3-propionic acid (IPA) in rats exposed to chlorpyrifos (CPF) alone at 5 mg/kg body weight or co-administered with IPA at 12.5 and 25 mg/kg for 14 days. Behavioral data indicated that IPA significantly (p < 0.05) abated CPF-mediated anxiogenic‐like behaviors with concomitant improvement in the locomotor and exploratory behaviors as substantiated by track plots and heat maps data. Also, IPA mitigated CPF-mediated diminution in cholinergic and antioxidant defense systems whereas it markedly improved thioredoxin level and thioredoxin reductase activity in cerebral and cerebellar tissues of the animals. Co-administration of IPA significantly enhanced anti-inflammatory cytokine, interleukin-10 but suppressed oxidative and inflammatory stress, caspase‐9 and caspase-3 activation with concomitant reduction in 8-hydroxy-2′-deoxyguanosine (8-OHdG) level and histological damage. Collectively, IPA‐mediated neuroprotection involves modulation of cholinergic and redox-regulatory systems, inflammatory stress, apoptotic responses and DNA damage in cerebrum and cerebellum of rats. •Influence of IPA on CPF-induced neurotoxicity was studied in rats.•IPA abated CPF-mediated aberrant behavior in rats.•IPA inhibited CPF-induced oxidative injury in brain structures.•IPA abated CPF-induced inflammation and caspase 3 activation.•IPA ameliorated CPF-induced DNA damage and histological lesions.