Anat Cell Biol.  2010 Dec;43(4):317-324. 10.5115/acb.2010.43.4.317.

Lipoic acid suppresses compound 48/80-induced anaphylaxis-like reaction

• Choi YH
• Chai OH
• Han EH
• Choi SY
• Kim HT
• Song CH

• KMID: 1455346
• DOI: http://doi.org/10.5115/acb.2010.43.4.317

Abstract

Alpha-lipoic acid (LA), a naturally occurring dithiol compound, is an essential cofactor in metabolic reactions involved in energy utilization. LA improves glycemic control, reduces diabetic polyneuropathies, atherosclerosis, and allergic inflammation. The effects of LA on mast cell-mediated anaphylactic reactions, however, are unknown. LA dose-dependently inhibited systemic and passive cutaneous anaphylaxis-like reactions in mice induced by compound 48/80, a condensation product of N-methyl-p-methoxyphenethylamine and formaldehyde. Pretreatment with LA, prior to induction of the systemic anaphylaxis-like reaction with compound 48/80, reduced plasma histamine levels in a dose-dependent manner. In our in vitro study, LA decreased histamine release from rat peritoneal mast cells (RPMCs) triggered by compound 48/80. Moreover, an increase in calcium uptake activated by compound 48/80 was inhibited by LA. LA also significantly elevated intracellular cyclic adenosine-3',5' monophosphate (cAMP) levels in RPMCs. This inhibition of mediator release from RPMCs may be due to inhibition of calcium uptake and augmentation of intracellular cAMP levels. Based on these results, we suggest that LA may be a potential remedy for allergy-related diseases.

Keyword

Mast cells; Immediate-type hypersensitivity; Histamine; Calcium; cAMP

MeSH Terms

Anaphylaxis
Animals
Atherosclerosis
Calcium
Diabetic Neuropathies
Formaldehyde
Histamine
Histamine Release
Inflammation
Mast Cells
Mice
Plasma
Rats
Thioctic Acid
Toluene
Calcium
Formaldehyde
Histamine
Thioctic Acid
Toluene

Figure

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  Fig. 1 Effect of lipoic acid (LA) on rat peritoneal mast cell (RPMC) viability. RPMCs were treated with various concentrations of LA for 2 h. RPMC viability was determined by MTT assay and the percentage of viability was calculated as a ratio of A570 of control cells (treated with HEPES-Tyrode's buffer solution). Each data value represents the mean±standard error of the mean (SEM) of five independent experiments.

• 

  Fig. 2 Inverted light microscopy of RPMCs. (A) Normal RPMCs in HEPES-Tyrode's buffer solution. (B) Degranulated RPMCs after the addition of compound 48/80. (C) RPMCs observed within 10 min after the addition of LA (4 mM) show similar findings as those seen in (A). (D) RPMCs pretreated with LA observed within 10 min after the addition of compound 48/80 show similar findings as those seen in (C). Bar=10 µm. Arrows represent RPMCs.

• 

  Fig. 3 Inhibitory effect of LA on compound 48/80-induced histamine release from RPMCs. RPMCs were preincubated with LA or disodium cromoglycate (DSCG) at 37℃ for 10 min prior to incubation with compound 48/80. Each bar represents the mean±SEM of five independent experiments. *P<0.05, significantly different from the control value.

• 

  Fig. 4 Inhibitory effect of LA on compound 48/80-induced calcium uptake in RPMCs. RPMCs were preincubated with LA at 37℃ for 10 min prior to incubation with compound 48/80. Each bar represents the mean±SEM of five independent experiments. *P<0.05, phosphate-buffered saline (PBS) alone compared to PBS plus compound 48/80 value; †P<0.05, significantly different from PBS plus compound 48/80 value.

• 

  Fig. 5 Effect of LA on cyclic adenosine-3',5' monophosphate (cAMP) levels in RPMCs. RPMCs were incubated with LA for the indicated time periods at 37℃. Each bar represents the mean±SEM of five independent experiments. *P<0.05, significantly different from samples treated with PBS alone.

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