Reversing the Adverse Biochemical Effects in Lead-Intoxicated Rats by N,N`- bis[(1,2-didehydro-1-hydroxy-2-thioxopyrid-4-yl)-carbonyl]- L-lysine

J Trace Elem Med Biol. 2018 Dec;50:93-99. doi: 10.1016/j.jtemb.2018.06.008. Epub 2018 Jun 15.

Abstract

N,N`-Bis[(1,2-didehydro-1-hydroxy-2-thioxopyrid-4-yl)-carbonyl]- L-lysine (HTPL) is a novel newly synthesized compound intended to be used for the chelation of lead in intoxicated animals. Subchronic lead intoxication experiments were carried out on Wistar male rats; these rats were intoxicated with lead and then treated with HTPL. Results were compared with those obtained with known compounds used for lead chelation therapy, such as disodium ethylnediaminetetraacetic acid (CaNa2EDTA) and meso-2,3-dimercaptosuccininc acid (DMSA), using different routes of administration. Biological samples of whole blood and urine were collected and analyzed for urinary proporphyrins, δ-aminolevulinic acid dehydratase, and zinc protoporphyrin. Results revealed that HTPL can remarkably reverse the toxic effects of lead intoxication at biochemical levels. Additionally, results showed that this agent is as good or even more potent than calcium disodium ethylnediaminetetraacetic acid (CaNa2EDTA) and meso-2,3-dimercaptosuccininc acid (DMSA) in reversing the toxic effect of lead. More importantly, HTPL was found effective when administrated intraperitoneally and orally.

Keywords: Aminolevulinic acid dehydratase; Chelation therapy; Rats; Subchronic lead poisoning; Urinary proporphyrins; Zinc protoporphyrin.

MeSH terms

  • Animals
  • Chelating Agents / therapeutic use*
  • Chelation Therapy
  • Edetic Acid / therapeutic use
  • Lead / toxicity*
  • Lead Poisoning / drug therapy
  • Male
  • Porphobilinogen Synthase / metabolism
  • Protoporphyrins / therapeutic use
  • Rats
  • Rats, Wistar
  • Succimer / therapeutic use

Substances

  • Chelating Agents
  • Protoporphyrins
  • zinc protoporphyrin
  • Lead
  • Edetic Acid
  • Succimer
  • Porphobilinogen Synthase