Cysteine-induced hypoglycemic brain damage: an alternative mechanism to excitotoxicity

V Gazit1, R Ben-Abraham, R Coleman

  • 1Laboratory for Anesthesia, Pain and Neural Research, The Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.

Amino Acids
|March 26, 2004
PubMed

Insights

L-cysteine (L-Cys) causes neurotoxicity and severe hypoglycemia in mice. This neural damage is linked to L-Cys

Area of Science:

  • Neuroscience
  • Biochemistry
  • Toxicology

Background:

  • L-cysteine (L-Cys) neurotoxicity mechanisms remain unclear despite decades of research.
  • Previous studies link L-Cys injection in mice to tachypnea, tremor, convulsions, and death, alongside hypoglycemia.

Purpose of the Study:

  • To investigate the mechanisms behind L-cysteine-induced hypoglycemia and central neural damage.

Main Methods:

  • Neonatal ICR mice were injected with varying doses of L-cysteine (0.5-1.5 mg/g BW).
  • Blood glucose and insulin levels were measured up to 90 minutes post-injection.
  • Experiments were replicated in streptozotocin (STZ)-induced diabetic mice, followed by brain histology.

Main Results:

  • L-cysteine induced dose-dependent neurotoxicity and increased mortality in mice.
  • High L-cysteine doses (1.2-1.5 mg/g BW) caused severe hypoglycemia (glucose < 42 mg/dl).
  • In diabetic mice, L-cysteine increased insulin by 2.3-fold and reduced glucose by 50%, causing significant hippocampal neuron destruction (51%).

Conclusions:

  • L-cysteine injection triggers significant hypoglycemia and central neural damage, particularly in the hippocampus.
  • The observed neurotoxicity is reversible with glucose administration.
  • L-cysteine's neurotoxicity may be intrinsically linked to its potent hypoglycemic effect.

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