Effects of celecoxib in young rats: histopathological changes in tissues and alterations of oxidative stress/antioxidant defense system.

Celecoxib is increasingly being used in children with rheumatologic complaints. Although the particular concerns about the safety of the drug, there are only a small number of published studies in children. This study was performed to investigate the effects of celecoxib on oxidative stress and antioxidant enzyme activities as well as celecoxib-induced changes in liver, kidneys and stomach of young rats. Four weeks-old Wistar albino, female rats were used. Celecoxib was given by gavage for 14 days. Control rats received only vehicle. Blood and organs were taken under pentobarbital anesthesia. Plasma malondialdehyde levels were increased by treatment. Catalase activity was increased, while glutathione peroxidase activity was decreased. Superoxide dismutase and glucose-6-phosphate dehydrogenase activities was not changed by treatment. The reduced glutathione content of kidneys were higher, while there was no significant difference in liver content, as compared with controls. Significant changes were observed in serum parameters of rats treated with celecoxib. Histopathological evaluation of organs was done by an experienced pathologist unaware of the treatment. Results of the present study indicated the alterations of oxidant/antioxidant status and histopathological changes in tissues of young rats treated with celecoxib.

Permeation studies of indomethacin from different emulsions for nasal delivery and their possible anti-inflammatory effects.

The purpose of this research was to develop an emulsion formulation of indomethacin (IND) suitable for nasal delivery. IND was incorporated into the oil phases of oil in water (O/W) and water in oil (W/O) emulsions. For this purpose, different emulsifying agents (Tween 80, Span 80 and Brij 58) were used in two emulsion formulations. When the effects of several synthetic membranes (nylon, cellulose, cellulose nitrate) were compared with the sheep nasal mucosa, the cellulose membrane and sheep nasal mucosa showed similar permeation properties for O/W emulsion (P > 0.05). To examine the absorption characteristics of IND, the anti-inflammatory properties of intravenous solution of IND, intranasal O/W emulsions of IND (with or without enhancers) and intranasal solution of IND (IND-Sol) were investigated in rats with carrageenan-induced paw edema. When citric acid was added to the nasal emulsion, the anti-inflammatory activity was similar to that of intravenous solution (P > 0.05). Finally, it was concluded that, intranasal administration of IND emulsion with citric acid may be considered as an alternative to intravenous and per oral administrations of IND to overcome their adverse effects.

Transdermal delivery of diclofenac sodium through rat skin from various formulations.

The aim of this study was to evaluate and compare the in vitro and in vivo transdermal potential of w/o microemulsion (M) and gel (G) bases for diclofenac sodium (DS). The effect of dimethyl sulfoxide (DMSO) as a penetration enhancer was also examined when it was added to the M formulation. To study the in vitro potential of these formulations, permeation studies were performed with Franz diffusion cells using excised dorsal rat skin. To investigate their in vivo performance, a carrageenan-induced rat paw edema model was used. The commercial formulation of DS (C) was used as a reference formulation. The results of the in vitro permeation studies and the paw edema tests were analyzed by repeated-measures analysis of variance. The in vitro permeation studies found that M was superior to G and C and that adding DMSO to M increased the permeation rate. The permeability coefficients (Kp) of DS from M and M+DMSO were higher (Kp = 4.9 x 10(-3) +/- 3.6 x 10(-4) cm/h and 5.3 x 10(-3) +/- 1.2 x 10(-3) cm/h, respectively) than the Kp of DS from C (Kp = 2.7 x 10(-3) +/- 7.3 x 10(-4) cm/h) and G (Kp = 4.5 x 10(-3) +/- 4.5 x 10(-5) cm/h). In the paw edema test, M showed the best permeation and effectiveness, and M+DMSO had nearly the same effect as M. The in vitro and in vivo studies showed that M could be a new, alternative dosage form for effective therapy.