Nitrous oxide abuse in the emergency practice, and Review of toxicity mechanisms and potential markers. (April 2022)

• Record Type: Journal Article
• Authors: Joncquel Chevalier-Curt, Marie; Grzych, Guillaume; Tard, Céline; Lannoy, Julien; Deheul, Sylvie; Hanafi, Riyad; Douillard, Claire; Vamecq, Joseph
• Is Part Of: Food and chemical toxicology. Volume 162(2022)
• Publication Date: 2022-04
• Subjects: Nitrous oxide abuse -- Cobalamins -- Vitamin B12 -- Methionine synthase -- Methylmalonyl-CoA mutase -- Methylation cycle -- Folate cycle -- Homocysteine -- Biological markers; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2022.112894
• Languages: English
• ISSNs: 0278-6915

Abstract

Abstract: Nitrous oxide (N2 O) toxicity is a concern common to several medical fields. Here, retrospective study of four N2 O abuses with neurological signs in the emergency practice provides a preliminary basis for a metabolic Discussion/Review. This latter highlights N2 O abuse as pathology of DNA/RNA/protein methylations, for instance consistent with impairments of protein arginine methyltransferases involved in myelinogenesis and myelopathy in patients. Basically, pathogenesis starts with oxidation by N2 O of coordinated cobalamine cobalt ions at enzyme sites with impairments of vitamin-B12-dependent pathways. Methionine synthase (methylcobalamine) and methymalonyl-CoA mutase (adenosylcobalamine) are inactivated and cofactor-depleted, respectively. The number of impacted pathways (folate cycle, methylation cycle, S -adenosylmethionine-dependent methyltransferases, transulfuration pathway, Krebs cycle fueling by methylmalonyl-CoA, glutathione synthesis) explains the variety of potential research/laboratory markers, and may provide new clues and future angles to explore N2 O toxicity. Overall, homocysteine measurements obviously help diagnosis of N2 O abuses. Additional markers may include vitamin-B12, methionine, methylmalonate, dimethylglycine, sarcosine, S -adenosylmethionine to S -adenosylhomocysteine ratio, various S -adenosylamino acids, S -adenosylmethionine-dependent cellular methylations, and additional analytes (propionylcarnitine, propionylglycine, cystathionine and derived metabolites, methylated amino acids [eg arginine], betaine). Highlights: Recreational use of N2 O can reach 100 to 300 cartridges/day, and cause neurological deterioration. N2 O by oxidising the coordinated cobalt ion disrupts cobalamin (vitamin B12)-dependent pathways. N2 O disrupts folate, methylation cycles; DNA, RNA, protein methylations; glutathione synthesis. Laboratory markers include increased plasma homocysteine and numerous metabolites reviewed. Treatment of abuse is cessation of N2 O consumption and supplementation with vitamins B12 and B6.