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Abstract
Male wister rats were subdivided into normal group, LPS treated rats (model of ALI), saline treated group, ALI+ simvastatin treated group, ALI+ rosuvastatin treated group, ALI+methylprednisolone treated group, ALI+ combination therapy of methylprednisolone with either simvastatin or rosuvastatin groups. Lung tissue TNF Ü , IL-1Ý, myeloperoxidase, malondialdehyde, total proteins and lung histopathology were assessed at 24 hours, 72 hours and on the 7th day after induction of ALI. Serum AST, ALT, creatinine phosphokinase, creatinine were assessed at the end of the experiment. The effects of simvastatin and rosuvastatin treatment on the Ach induced contractions of tracheal rings isolated from rats with ALI were studied. RESULTS: The LPS induced ALI group showed significant increase in TNFÜ , IL-1Ý, myeloperoxidase, malondialdehyde, total lung proteins and pathological score. Treatment of rats with ALI with simvastatin, rosuvastatin or methylprednisolone resulted in significant decrease in these elevated parameter at 24 hours, 72 hours and on the 7th day as compared to the untreated model group. Methylprednisolone therapy alone was significantly effective than simvastatin therapy alone in reducing all parameter measured. Meanwhile it was more effective in decreasing TNF Ü and IL-1Ý in ALI than rosuvastatin therapy alone. Rosuvastatin was more significantly effective in reducing the level of all parameter measured at the end of the present study than simvastatin therapy. Regarding the combination therapy, methylprednisolone with rosuvastatin showed the most significant reduction of all parameters all through the experiment. Moreover rosuvastatin therapy in ALI did not significantly affect AST, ALT, serum creatinine, or kreatinine kinase. CONCLUSIONS: Simvastatin or rosuvastatin therapy could be beneficial in management of ALI either alone or in combination with methylprednisolone. The most significant improvement of the measured ALI parameters occurred with rosuvatatin and methylprednisolone combination therapy. Rosuvastatin was more safe than simvastatin. These results could offer a new opportunity in management of ALI