The protective role of L-carnitine on oxidative stress, neurotransmitter perturbations, astrogliosis, and apoptosis induced by thiamethoxam in the brains of male rats

Naunyn Schmiedebergs Arch Pharmacol. 2024 Jun;397(6):4365-4379. doi: 10.1007/s00210-023-02887-7. Epub 2023 Dec 15.

Abstract

Synthetic organic insecticides such as pyrethroids, organophosphates, neonicotinoids, and others have the potential to disrupt ecosystems and are often toxic to humans. Thiamethoxam (TMX), a neonicotinoid insecticide , is a widely used insecticide with neurotoxic potential. L-Carnitine (LC) is regarded as the "gatekeeper" in charge of allowing long-chain fatty acids into cell mitochondria. LC is an endogenous chemical that is renowned for its prospective biological activity in addition to its role in energy metabolism. This study investigated the protective effects of LC against TMX-induced neurotoxicity in male Wistar rats. For 28 days, animals were divided into four groups and treated daily with either LC (300 mg/kg), TMX (100 mg/kg), or both at the aforementioned doses. Our results revealed marked serum lipid profile and electrolyte changes, declines in brain antioxidants and neurotransmitters (acetylcholine, dopamine, and serotonin levels) with elevations in thiobarbituric acid reactive substances and proinflammatory cytokine levels, as well as acetylcholinesterase and monoamine oxidase brain activity in TMX-treated rats. TMX also increased the expression of caspase-3 and glial fibrillary acidic protein. In contrast, pretreatment with LC attenuated TMX-induced brain injury by suppressing oxidative stress and proinflammatory cytokines and modulating neurotransmitter levels. It also ameliorated the expression of apoptotic and astrogliosis markers. It could be concluded that LC has antioxidant, anti-inflammatory, anti-astrogliosis, and anti-apoptotic potential against TMX neurotoxicity.

Keywords: l-Carnitine; Apoptosis; Astrogliosis; Oxidative stress; Thiamethoxam; Wistar rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / metabolism
  • Animals
  • Antioxidants / pharmacology
  • Apoptosis* / drug effects
  • Brain* / drug effects
  • Brain* / metabolism
  • Brain* / pathology
  • Carnitine* / pharmacology
  • Caspase 3 / metabolism
  • Cytokines / metabolism
  • Gliosis / chemically induced
  • Gliosis / pathology
  • Gliosis / prevention & control
  • Insecticides* / toxicity
  • Male
  • Monoamine Oxidase / metabolism
  • Neuroprotective Agents* / pharmacology
  • Neurotoxicity Syndromes / drug therapy
  • Neurotoxicity Syndromes / etiology
  • Neurotoxicity Syndromes / metabolism
  • Neurotoxicity Syndromes / pathology
  • Neurotoxicity Syndromes / prevention & control
  • Neurotransmitter Agents / metabolism
  • Oxidative Stress* / drug effects
  • Rats
  • Rats, Wistar*
  • Thiamethoxam* / pharmacology
  • Thiamethoxam* / toxicity