Capsazepine, rimonabant, WIN55, 212-2 and lidocaine attenuated acute lung inflammation induced by co-exposure of capsaicin and cigarette smoke extract in rats

Abstract

Cigarette smoking is central to the pathogenesis of lung inflammatory diseases like asthma and chronic obstructive pulmonary disease (COPD). The study evaluated the effect of drugs belonging to pharmacologically different classes <i>viz</i>., capsazepine, a TRPV1 antagonist; rimonabant, a CB1 antagonist; WIN 55,212-2, a cannabimimetic; and lidocaine, a local anaesthetic in lung inflammation induced by cigarette smoke extract (CSE) and Capsaicin. Capsazepine (10 mg/kg), rimonabant (3 mg/kg), WIN 55,212-2 (3 mg/kg), and lidocaine (1 mg/kg), were intraperitoneally (i.p.) administered to Wistar rats. They were then exposed to capsaicin (20 mg of <i>Capsicum oleoresin</i>/kg body weight i.p.) followed by intratracheal administration of CSE (1.3 mL/kg). After 24 hours, Bronchoalveolar lavage (BAL) was performed, and lungs were removed and processed to assess the various lung inflammatory parameters. Co-exposure with capsaicin and CSE lead to rise in leucocyte counts and total proteins in bronchoalveolar lavage fluid (BALF). Pretreatment with capsazepine, rimonabant, WIN 55,212-2 and lidocaine significantly abrogated the lung inflammation. They also prevented the rise in lung tumor necrosis factor α (TNF α), myeloperoxidase (MPO) and matrix metalloproteinase 9 (MMP 9) activities. This was further corroborated with histopathological evidences. The study reveals that these drugs act through distinct mechanisms to abate capsaicin- and CSE-induced lung inflammation in rats. The effects may be attributed to direct or indirect inhibition of the inflammatory cascade after transient receptor potential vanilloid (TRPV1) channel activation by CSE and capsaicin. The impact of the test drugs in reducing capsaicin plus CSE induced lung inflammation makes them potential candidates for the treatment of lung inflammatory diseases.