Amelioration of lead- and cadmium-induced rat tracheal hypercontraction by linalool and eugenol

Abstract

Relative contribution of various pathways to non-acute hypercontraction produced by low concentrations of lead (Pb) and cadmium (Cd) and its amelioration by eugenol and linalool was examined in rat tracheal system. Saturating effect producing concentrations of nitric oxide (NO) donor (sodium nitroprusside; 1 μM), reactive oxygen species (ROS) inhibitor (apocynin; 100 μM), and cyclooxygenase inhibitor (indomethacin; 100 μM) produced 38%, 55%, and 40% inhibition of hypercontraction in Pb-exposed and 27%, 45%, and 38% in Cd-treated trachea, respectively. These inhibitors decreased contraction by 20%, 29%, and 28%, respectively, in tissue indicating that ROS are the major contributors in both Pb- and Cd-induced hypercontraction. Depletion of NO contributes significantly to Pb-induced hypercontraction but not to Cd. Cyclooxygenases were found to play a non-significant role in hypercontraction produced by both pollutants. Relaxations provided by saturating concentrations of eugenol (100 μM) and linalool (100 μM) in the presence and absence of three inhibitors suggest that major effect of eugenol originates from inhibition of ROS whereas that of linalool from inhibition of cyclooxygenase signaling cascades. This correlates well with relaxation provided by eugenol and linalool in pollutant-exposed tracheal rings. Activities of key enzymes – superoxide dismutase, glutathione peroxidase, and nitric oxide synthase – showed that Pb generated oxidative stress by direct binding to these enzymes and Cd by other mechanisms.