Efficacy assessment of co-treated alpha-ketoglutarate and N-acetyl cysteine against the subchronic toxicity of cyanide in rats

Abstract

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.

Aşiri Doz Keten Tohumu (Linum Usitatissimum L.) Tüketi̇mi̇ Ratlarda Karaci̇ğer Hasarina Neden Olur Mu?

“…Studies have shown that in rats treated with cadmium, the balance of prooxidant / antioxidant was disrupted, lipid peroxidation increased, and total antioxidant capacity decreased (28,29). Cyanide hepatotoxicity increases oxidation with a similar effect to cadmium while reducing the antioxidant parameters (33). It's known that while reactive oxygen species (ROS) are produced in metabolic and physiological processes, harmful oxidative reactions can occur in organisms that remove them through enzymatic and non-enzymatic antioxidative mechanisms (29-31).…”

Cyanide poisoning- an update

“…It also binds with nitric oxide (NO), restoring blood pressure in poisoned patients (50). There are substances under active research and future that can be developed as efficient antidotes such as Alpha-Ketoglutarate, Cobinamide, Dihydroxyacetone, Hydroxylamine, Salfanegen, and S.methyl Mthylthiosulfonate (MTSO) (53,54,55,56,57).…”

Superior Plants with Significant Amounts of Cyanide and Their Toxicological Implications

“…Treatment of poisoning from ingestion of cyanogenic sources is similar to treatment for CN poisoning (Barceloux, 2009;Houzé et al, 2018). Clinical signs of acute CN poisoning in humans may include vomiting, epigastric pain, diarrhea, rapid breathing, decreased blood pressure, rapid pulse, dizziness, headache, mental confusion, stupor, cyanosis with spasms, seizures, and respiratory paralysis (Bradberry and Vale, 2016;Satpute et al, 2019). Death from CN poisoning can occur when the cyanide level exceeds the limit that an individual is able to detoxify (Onojah and Odin, 2015).…”