Bergapten modulates ovalbumin-induced asthma

Abstract

Prior studies on the anti-inflammatory compound bergapten have shown promise in avert- ing allergic airway hyperresponsiveness. This study sought to establish its possible role in modulating an immunologically-induced airway inflammation and hyperresponsiveness in an ovalbumin model of asthma. Asthma is characterised by inflammation and constriction of the airway passages. Therapy is aimed at bronchodilation and reducing inflammation. Histamine is an inflammatory mediator and involved in immune reactions. It is released from mast cells which are important sentinel cells of the innate immune system involved in the inflammatory response. In the asthma model, ovalbumin solution (2 mg ovalbumin) was administered i.p. as a sensitisation dose on day 1 and on day 14 as a booster dose to sensitise the immune system. This was followed by a 10-day challenge on days 21 – 30 us- ing aerosolised ovalbumin (1% w/v dissolved in phosphate-buffered saline, PBS) at a cut-off latency of 10 min. Bergapten was administered at doses of 3 - 30 mg kg−1 p.o. 1 h prior to each challenge. Times to pre-convulsive dyspnoea were recorded. Guinea-pigs were sacri- ficed and lungs harvested for histological and antioxidant studies. In determining the effect of bergapten on histamine, an isolated guinea pig ileum preparation by the administration of bergapten (1 – 10 μg ml−1 ) in the presence of histamine. Bergapten increased times to pre-convulsive dyspnoea in the ovalbumin challenge and reduced pathological damage to bronchial tissue. The deposition of collagen around bronchioles was minimised. Antioxi- dant studies showed higher catalase and superoxide dismutase activity in groups treated with bergapten. Bergapten produced a rightward shift on the Schild plot analysis with a slope of 1.4 and a pA2 value of 9.3 was obtained in the isolated tissue experiment which confirms that bergapten acts as an antagonist on histaminic H1 receptors. Bergapten mod- ulates inflammation in ovalbumin-induced asthma and antagonises histamine at the H1 receptor.