title: Effects of rebamipide on nephrotoxicity associated with selected NSAIDs in rats.
abstract: 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.
authors.affiliation: Gatton College of Pharmacy, East Tennessee State University, Johnson City, TN 37614, USA.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Wood
authors.affiliation: Gatton College of Pharmacy, East Tennessee State University, Johnson City, TN 37614, USA.
authors.forename: Jarrett E
authors.initials: JE
authors.lastname: Wyatt
authors.affiliation: Department of Pharmaceutical Sciences, Gatton College of Pharmacy, East Tennessee State University, Johnson City, TN 37614, USA.
authors.forename: Kenny W
authors.initials: KW
authors.lastname: Bullins
authors.affiliation: Department of Pharmaceutical Sciences, Gatton College of Pharmacy, East Tennessee State University, Johnson City, TN 37614, USA.
authors.forename: Angela V
authors.initials: AV
authors.lastname: Hanley
authors.affiliation: Division of Laboratory Animal Resources, East Tennessee State University, Johnson City, TN 37614, USA.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Hanley
authors.affiliation: College of Medicine, Department of Pathology, East Tennessee State University, Johnson City, TN 37614, USA.
authors.forename: James W
authors.initials: JW
authors.lastname: Denham
authors.affiliation: Department of Pharmaceutical Sciences, Gatton College of Pharmacy, East Tennessee State University, Johnson City, TN 37614, USA.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Panus
authors.affiliation: Department of Pharmaceutical Sciences, Gatton College of Pharmacy, East Tennessee State University, Johnson City, TN 37614, USA. Electronic address: harirfor@etsu.edu.
authors.forename: Sam
authors.initials: S
authors.lastname: Harirforoosh
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D000068579:Celecoxib; D015815:Cell Adhesion Molecules / Q000652:urine; D003404:Creatinine / Q000652:urine; D004008:Diclofenac / Q000009:adverse effects; D015232:Dinoprostone / Q000097:blood; D004347:Drug Interactions; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000097:blood / Q000139:chemically induced* / Q000473:pathology / Q000652:urine; D008297:Male; D009569:Nitric Oxide / Q000097:blood; D011188:Potassium / Q000652:urine; D011720:Pyrazoles / Q000009:adverse effects; D015363:Quinolones / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000652:urine; D013449:Sulfonamides / Q000009:adverse effects
chemical_list: D000409:Alanine; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D000068579:Celecoxib; D015815:Cell Adhesion Molecules; D003404:Creatinine; D004008:Diclofenac; D015232:Dinoprostone; D009569:Nitric Oxide; D011188:Potassium; D011720:Pyrazoles; D015363:Quinolones; D012964:Sodium; D013449:Sulfonamides; C110936:Havcr1 protein, rat; C052785:rebamipide
keywords: Cyclooxygenase; Electrolyte; Kidney; NSAIDs; Prostaglandin; Rebamipide