285-291Cigarette smoke (CS)
is a rich source of radicals, predisposing the cell to oxidative stress
resulting in inflammation. Chronic inflammation is a recognized risk factor for
carcinogenesis. Cyclooxygenase-2 (COX-2) is a mediator of inflammatory pathway
and may, therefore, contribute to carcinogenesis. There are several reports
that suggest the association between CS and COX-2 associated risk to cancer. In
the present study, we examined the role of celecoxib
(a selective COX-2 inhibitor) in modulating the oxidative stress caused by CS
inhalation in mice. CS exposure for a period of 10 weeks caused oxidative
stress in the pulmonary and hepatic tissues, as evident from the increase in
lipid peroxidation levels (LPO) and decrease in reduced glutathione (GSH)
levels. Celecoxib (125 mg/kg body weight for 8 weeks) administration to CS
inhaling mice reduced the oxidative stress by decreasing the LPO levels and
enhancing the GSH levels in comparison to the CS-exposed group. CS exposure
repressed the enzymatic antioxidant defense system, as evident from the
decrease in catalase (CAT) and superoxide dismutase (SOD) activities.
Co-adminstration of celecoxib considerably reversed the changes in the
enzymatic antioxidant defense system. Histopathological studies of lungs showed
that CS exposure induced alveolar wall destruction and air space enlargement.
In co-treated group, the alveolar septa were thicker than normal with apparent
infiltration of inflammatory cells. In CS-exposed group, hepatic tissue
exhibited vacuolization and macrophage infiltration. Co-treatment with
celecoxib restored the normal histoarchitechture in hepatic tissues of CS
inhaling mice. Thus, the present study demonstrated that celecoxib adminstration
reduced the oxidative stress-mediated risk to carcinogenesis, due to its
ability to boost the antioxidant defense system