Aflatoxin B1-induced redox imbalance in the hippocampus and cerebral cortex of male Wistar rats is accompanied by altered cholinergic, indoleaminergic, and purinergic pathways: Abatement by dietary rutin

Toxicon. 2024 Feb 23:239:107595. doi: 10.1016/j.toxicon.2024.107595. Epub 2024 Jan 10.

Abstract

The neurotoxic impact of dietary exposure to aflatoxin B1 (AFB1) is well documented in experimental studies. Rutin is a phytochemical with prominent anti-inflammatory and antioxidant activities. There is an information gap on the influence of rutin on AFB1-induced neurotoxicity. This study investigated the influence of rutin on neurobehavioral and biochemical abnormalities in male Wistar rats (six weeks old) orally treated with AFB1 (0.75, and 1.5 mg/kg body weight) or co-administered with rutin (50 mg/kg) for 30 uninterrupted days. Results indicate that AFB1-induced depression-like behavior by Tail Suspension Test (TST) and cognitive impairment by Y-maze was abated following rutin co-administration. Abatement of AFB1-induced decreases in acetylcholinesterase (AChE) activity, and increased antioxidant status, by rutin was accompanied by a marked reduction in oxidative stress markers and increased hydrolysis of the purinergic molecules in the cerebral cortex and hippocampus of rats. Additionally, rutin co-treatment abrogated AFB1-mediated elevation of interleukin-6 (IL-6), nitric oxide (NO) levels, and activity of myeloperoxidase (MPO). Correspondingly, rutin co-treatment lowered the activity and immunocontent of immunosuppressive indoleamine 2, 3-dioxygenase (IDO). Further, rutin co-treatment prevented histological injuries in the cerebral cortex and hippocampus. In conclusion, abatement of AFB1-induced neurobehavioral abnormalities by rutin involves the mechanisms of anti-inflammatory, antioxidant, and regulation of cholinergic, purinergic, and indoleaminergic pathways in rats.

Keywords: Dietary flavonoids; Kynurenine; Mycotoxins; Neurotoxin; Oxido-inflammatory stress.

MeSH terms

  • Acetylcholinesterase
  • Aflatoxin B1* / toxicity
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Antioxidants* / metabolism
  • Antioxidants* / pharmacology
  • Cerebral Cortex / metabolism
  • Cholinergic Agents / metabolism
  • Cholinergic Agents / pharmacology
  • Hippocampus
  • Male
  • Oxidation-Reduction
  • Oxidative Stress
  • Rats
  • Rats, Wistar
  • Rutin / pharmacology

Substances

  • Aflatoxin B1
  • Antioxidants
  • Rutin
  • Acetylcholinesterase
  • Cholinergic Agents
  • Anti-Inflammatory Agents