Effect of Sodium R-Lipoate and Enzymatically-Modified Isoquercitrin on Mast Cell-Dependent Anaphylactic Reactions

Abstract

Anaphylaxis is a potentially life-threatening allergic reaction. Due to high frequency of anaphylaxis world- wide and limited benefits of using synthetic antiallergic drugs, developing of new safer and more effective therapeutic agents from natural compounds that are chemically/enzymatically-modified has become urgent challenge in improving patient’s health. Therefore, the present study aimed to evaluate/compare the modulatory effects of sodium salt of R-lipoic acid (NaRLA) and enzymatically-modified isoquercitrin (EMIQ) at two different doses (50 and 100 mg/kg body weight “b.w”, given orally), in a mouse models of both local/systemic immunoglobulin (Ig) E-independent and IgE-dependent anaphylactic reactions, as well as stress-induced gastric ulceration, in comparison with sulfasalazine (SSZ) as a reference drug. The data showed that the pre-treatment of mice with NaRLA or EMIQ (especially at 100 mg/kg b.w) completely succeeded, as SSZ, in reducing the hind paw edema induced by either histamine or compound 48/80 (Cpd 48/80). Furthermore, they suppressed the IgE-independent peritoneal mast cell degranulation and anaphylactic shock caused by Cpd 48/80 (in a dose-dependent manner) and alleviated significantly (P<0.001) the histamine release from the mouse peritoneal mast cells, like SSZ. Also, they protected the ovalbumin (OVA)-sensitized mice from mortality in a dose-dependent manner, by reducing the elevated peritoneal histamine and interleukin-4 levels along with amelioration in the associated gastrointestinal and lung histopathological changes. This was accompanied with suppression of IgE-dependent skin mast cell degranulation as evidenced by the significant alleviation (P<0.001) of the active cutaneous anaphylactic reaction in the left ear of the OVA-sensitized mice. In addition, their use was associated with attenuating both gastric histopathological and biochemical alterations, as well as decreasing the percentage of degranulated mesenteric mast cells in the water-restraint stress mouse model towards the control values. In conclusion, our results provide possibility that both NaRLA and EMIQ may serve as an effective therapeutic agents for mast cells-mediated anaphylactic reactions via suppression of mast cell degranulation and histamine release without risks of inducing gastric ulcers.