Effects of rebamipide on nephrotoxicity associated with selected NSAIDs in rats

Use of nonsteroidal anti-inflammatory drugs (NSAIDs) is primarily limited by renal and gastrointestinal adverse effects. Rebamipide suppresses gastric mucosal injury when administered with NSAIDs. This study aimed to determine rebamipide's influence upon renal effects following concomitant use with celecoxib or diclofenac. On day 0, rats were randomly divided into 6 groups (n≥6). On days 1 and 2, three groups received placebo and three groups were administered rebamipide (30 mg/kg) twice daily. On day 3, the rats treated with placebo received another dose of placebo and ten minutes later a single dose of celecoxib (40 mg/kg), diclofenac (10mg/kg), or placebo, respectively. The rats treated with rebamipide received one more dose of rebamipide and ten minutes later one single dose of celecoxib, diclofenac, or placebo, respectively. Urine and blood samples were collected on days 0, 2, and 3. Sodium and potassium excretion rates decreased significantly in the rats treated with celecoxib, diclofenac, rebamipide plus celecoxib, or rebamipide plus diclofenac on day 3. Blood urea nitrogen (BUN) levels significantly increased in placebo plus diclofenac and rebamipide plus diclofenac groups on day 3. Comparing the two groups, the levels of BUN was significantly higher in the rebamipide plus diclofenac group compared to that of placebo plus diclofenac group. Concomitant administration of rebamipide with either NSAID caused a rise in concentrations of urinary kidney injury molecule-1. Histopathological evaluations revealed an intensified NSAID-induced tubular necrosis by rebamipide. Based upon the results obtained, concomitant administration of rebamipide with NSAIDs enhances the effect of NSAIDs on tubular injury.