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Published on: November 6, 2017
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.
Abstract:
Central neural damage caused by L-cysteine (L-Cys) was first reported more than 30 years ago. Nevertheless, the exact mechanisms of L-Cys-mediated neurotoxicity are still unclear. Preliminary study in mice demonstrated that, following L-Cys injection, animals developed tachypnea, tremor, convulsions, and death in conjunction with documented hypoglycemia. The aim of the present study was to further investigate the mechanism of L-Cys-mediated hypoglycemic effect and neural damage. Neonatal ICR mice (n=6) were injected with L-Cys (0.5-1.5 mg/g body weight [BW]), and their blood glucose and insulin levels were determined up to 90 min following the injection. Experiments were repeated in chemically (streptozotocin [STZ]) pancreatectomized animals. Brain histology was assessed. Mice injected with L-Cys exhibited dose-dependent neurotoxicity and higher mortality as compared with controls. L-Cys (1.2-1.5 mg/g BW) caused severe hypoglycemia (glucose<42 mg/dl) ( P<0.001). In STZ-treated (diabetic) animals, L-Cys (1.5 mg/g BW) increased plasma insulin levels 2.3-fold and decreased serum glucose levels by 50% ( P<0.01). Brain histology revealed destruction of as much as 51% of hippocampal neurons in the L-Cys-treated mice but not in the glucose-resuscitated animals. These findings suggest that L-Cys injection can cause pronounced hypoglycemia and central neural damage which is glucose reversible. Since L-Cys is chemically different from the other excitatory amino acids (glutamate and aspartate), L-Cys-mediated neurotoxicity may be connected to its hypoglycemic effect.
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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