L-carnitine and Co Q10 ameliorate potassium dichromate -induced acute brain injury in rats targeting AMPK/AKT/NF-κβ

Abstract

Adenosine monophosphate-activated protein kinase (AMPK) has a crucial role in neuroprotection. It phosphorylates serine/threonine kinase (Akt) Substrate inhibiting the inflammatory responses induced by the nuclear factor-κB (NF-κB). Exposure to chromium VI dust among workers has been reported and induced brain injury, as the absorption of chromium through the nasal membrane has been found to deliver it directly to the brain. The study aimed to investigate the influence of administration of L-carnitine or/and Co Q10 as theraputic agents against potassium dichromate (PD)-induced brain injury via AMPK/AKT/NF-κβ signaling pathway. Brain injury was induced by PD intranasally as a single dose of 2 mg/kg, 24 h latter rats received L-carnitine (100 mg/kg; orally), Co Q10 (50 mg/kg; orally) and L-carnitine (50 mg/kg; orally) + Co Q10 (25 mg/kg; orally) respectively for 3 days. Locomotor activity was assessed before and at the end of the experiment, then, biochemical and histopathological investigations were assessed in brain homogenate. The exposure of rats to PD promoted oxidative stress and inflammation via an increase in MDA and a decrease in GSH brain contents with an increase in brain contents of TNF-α, IL-6, and NF-kβ and reduced AMPK and AKT brain contents as compared to the control group. Treatment with L-carnitine + Co Q10 ameliorated cognitive impairment and oxidative stress, decreased the brain contents of inflammatory mediators; TNF-α, IL-6, and NF-κβ elevated AMPK and AKT, as compared to each drug. Also, L-carnitine + Co Q10 administration restored morphological changes as degenerated neurons and necrosis. L-carnitine + Co Q10 play important role in AMPK/AKT/NF-κβ pathway that responsible for their antioxidant and anti-inflammatory effects against PD-induced brain injury in rats.