Anti-anaphylactic action of nordihydroguaiaretic acid in antigen sensitized guinea pigs.
Therapeutic natural products and medicinal herbs has gained popularity. The anti-antigenic action of the plant alkaloid nordihydroguaiaretic acid (NDGA) was studied in ovalbumin (OA)-sensitized guinea pigs. In one series of experiments conscious, non-sedated guinea pigs were challenged with OA aerosol. Specific airway resistance (SRAW) was monitored using a two-chambered whole-body plethysmograph. OA aerosol increased SRAWabove that produced by vehicle administration. Prior NDGA administration by a 1min 0.9% aerosol (w/vol) attenuated the increase in SRAWresulting from OA challenge. In the anesthetized guinea pig pretreated with indomethacin, pyrilamine and propranolol, intravenous OA injection increased intra-tracheal pressure above vehicle injection. Intravenous NDGA administration (5mg/kg) reduced the intra-tracheal pressure increases. In a third series of experiments plasma leukotriene C4was measured by radio-immunoassay in 3 groups challenged with OA aerosol: vehicle-treated OA-sensitized, OA-sensitized receiving NDGA and vehicle treated guinea pigs. NDGA pretreatment reduced plasma LTC4in response to OA challenge in OA sensitized guinea pigs. This study demonstrates that NDGA is an effective antigenic agent when given by aerosol or intravenous injection in either conscious or anesthetized guinea pigs, respectively. The mechanism of action of NDGA is presumed primarily be due to the blockage of 5-lipoxygenase and therefore the synthesis of leukotrienes.
Department of Biomedical Sciences, School of Medicine, Creighton University, Omaha, NE, United States. Electronic address: dbergren@creighton.edu.
Dale R
DR
Bergren
Section of Pediatric Clinical Pharmacology and Toxicology, University of Arkansas Medical Sciences, Little Rock, AR, United States.
Jimmie L
JL
Valentine
D000336:Aerosols; D000403:Airway Resistance / Q000187:drug effects; D000704:Analysis of Variance; D000707:Anaphylaxis / Q000139:chemically induced / Q000188:drug therapy*; D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D006168:Guinea Pigs; D017997:Leukotriene C4 / Q000378:metabolism; D016859:Lipoxygenase Inhibitors / Q000627:therapeutic use*; D008297:Male; D009637:Masoprocol / Q000627:therapeutic use*; D010047:Ovalbumin / Q000633:toxicity; D010991:Plethysmography; D012044:Regression Analysis
D000336:Aerosols; D016859:Lipoxygenase Inhibitors; D017997:Leukotriene C4; D009637:Masoprocol; D010047:Ovalbumin
Airway responsiveness; Antigen; Guinea pigs; Leukotrienes; Nordihydroguaiaretic acid; Plethysmography