Gatton College of Pharmacy, East Tennessee State University, Johnson City, TN 37614, USA.
Department of Pharmaceutical Sciences, Gatton College of Pharmacy, East Tennessee State University, Johnson City, TN 37614, USA.
Eur J Pharmacol. 2013 Nov 15;720(1-3):138-46. doi: 10.1016/j.ejphar.2013.10.035. Epub 2013 Oct 24.
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.
非甾体抗炎药(NSAIDs)的使用主要受到肾和胃肠道不良反应的限制。瑞巴派特与 NSAIDs 联合使用时可抑制胃黏膜损伤。本研究旨在确定瑞巴派特与塞来昔布或双氯芬酸同时使用对肾的影响。第 0 天,大鼠随机分为 6 组(n≥6)。第 1 天和第 2 天,三组给予安慰剂,三组给予瑞巴派特(30mg/kg),每日两次。第 3 天,给予安慰剂的大鼠再给予一次安慰剂,十分钟后给予塞来昔布(40mg/kg)、双氯芬酸(10mg/kg)或安慰剂单次剂量。给予瑞巴派特的大鼠再给予一次瑞巴派特,十分钟后给予塞来昔布、双氯芬酸或安慰剂单次剂量。于第 0 天、第 2 天和第 3 天收集尿液和血液样本。第 3 天,与塞来昔布、双氯芬酸、瑞巴派特加塞来昔布或瑞巴派特加双氯芬酸治疗的大鼠尿钠和尿钾排泄率显著降低。第 3 天,安慰剂加双氯芬酸和瑞巴派特加双氯芬酸组的血尿素氮(BUN)水平显著升高。与安慰剂加双氯芬酸组相比,瑞巴派特加双氯芬酸组的 BUN 水平明显更高。这些结果表明,瑞巴派特与 NSAIDs 联合使用会导致尿肾损伤分子-1 浓度升高。组织病理学评估显示,瑞巴派特加重了 NSAIDs 引起的肾小管坏死。基于所获得的结果,瑞巴派特与 NSAIDs 联合使用增强了 NSAIDs 对肾小管损伤的作用。