Cyanide is an important industrial
pollutant, major occupational hazard, and a potential
chemical warfare agent. Its intentional or accidental exposure to humans is a big clinical problem because of its rapid mode of action. Certain plant origin foods also contain substantial amount of
cyanide and cause chronic toxicity. This study explores the protective efficacy of co-treatment of
alpha-ketoglutarate (AKG) and an
antioxidant N-acetyl
cysteine (NAC) against toxicity of subchronically exposed
cyanide in rats. We explore the effect of AKG + NAC co-treatment on oxidative stress,
inflammation, and histological changes induced due to long-term sublethal
cyanide exposure.
Cyanide induces oxidative stress by inhibiting metalloenzymes (
catalase and
superoxide dismutase) causing increase in lipid peroxidation (
malondialdehyde) and decrease in
reduced glutathione (GSH). It also increases the activity of
cyclo-oxygenase enzymes causing oxidative stress-mediated
inflammation in the brain.
Cyanide exposure also causes degenerative changes in the brain as shown in histology. It also causes pathology in liver and kidney. AKG is known to form cyanohydrins with
cyanide reducing the free
cyanide levels, and its combination with NAC showed overall improvement in by reducing the oxidative stress and subsequent
neuroinflammation. Their combination was also found to improve the histological outcome of vital tissues. AKG, an over-the-counter sport medicine, and the
antioxidant NAC per se did not show any detrimental effects in any tested parameter. Hence, oral treatment with AKG and NAC can be beneficial for the treatment of chronic
cyanide poisoning.