Dopamine-modified hyaluronic acid (DA-HA) as a novel dopamine-mimetics with minimal autoxidation and cytotoxicity

Redox Biol. 2024 Oct:76:103320. doi: 10.1016/j.redox.2024.103320. Epub 2024 Aug 20.

Abstract

Dopamine-modified hyaluronic acid (DA-HA) has been initially developed as an efficient coating and adhesion material for industrial uses. However, the biological activity and safety of DA-HA in the brain have not been explored yet. Here, we report a series of evidence that DA-HA exhibits similar functionality as dopamine (DA), but with much lower toxicity arising from autoxidation. DA-HA shows very little autoxidation even after 48-h incubation. This is profoundly different from DA and its derivatives including l-DOPA, which all induce severe neuronal death after pre-autoxidation, indicating that autoxidation is the cause of neuronal death. Furthermore, in vivo injection of DA-HA induces significantly lower toxicity compared to 6-OHDA, a well-known oxidized and toxic form of DA, and alleviates the apomorphine-induced rotational behavior in the 6-OHDA animal model of Parkinson's disease. Our study proposes that DA-HA with DA-like functionalities and minimal toxicity has a great potential to treat DA-related disease.

Keywords: And a 6-OHDA-Induced mouse model of Parkinson's disease; Autoxidation; DA-Induced cytotoxicity; Dopamine (DA); Dopamine-modified hyaluronic acid (DA-HA).

MeSH terms

  • Animals
  • Disease Models, Animal
  • Dopamine* / metabolism
  • Dopamine* / pharmacology
  • Humans
  • Hyaluronic Acid* / chemistry
  • Hyaluronic Acid* / pharmacology
  • Male
  • Mice
  • Neurons / drug effects
  • Neurons / metabolism
  • Oxidation-Reduction*
  • Oxidopamine*
  • Parkinson Disease / drug therapy
  • Parkinson Disease / metabolism
  • Rats

Substances

  • Hyaluronic Acid
  • Dopamine
  • Oxidopamine