Caffeine Potentiates the Nephrotoxicity of Mefenamic Acid on the Rat Renal Papilla

Abstract

The effect of caffeine given in combination with mefenamic acid on the renal papilla was studied. Sprague-Dawley rats were divided into four groups and gavage fed either control suspension, mefenamic acid, mefenamic acid and caffeine or caffeine alone for 4 months. Semiquantitative urinalysis was performed at 3 months and showed increased haematuria in the mefenamic acid and caffeine group. There were no significant differences in serum creatinine at sacrifice. Renal histology revealed more advanced papillary necrosis in rats gavage fed mefenamic acid and caffeine compared with all other groups (p < 0.0001). Rats fed mefenamic acid alone showed more damage than control and caffeine-fed groups (p < 0.0001, p < 0.0002, respectively). This suggests that caffeine potentiates the nephrotoxicity of the non-steroidal anti-inflammatory drug, mefenamic acid, on the rat renal papilla. The mechanism of this potentiation by caffeine is yet to be defined.

Hypoxia of the Renal Medulla — Its Implications for Disease

“…12 Prostaglandin E 2 inhibits active transport in the medullary thick ascending limb, 16 and the exogenous administration or endogenous stimulation of prostaglandin production protects it from hypoxic injury. 35 Long-term exposure to nonsteroidal antiinflammatory drugs causes analgesic nephropathy and medullary necrosis (po-tentiated by caffeine, 47 an antagonist of adenosine receptors).…”

Selective determination of mefenamic acid in the presence of 1000-fold excess paracetamol and caffeine using a multiwalled carbon nanotube–polymer composite electrode

“…[18] Creapigny et al reported that CAF potentiates the nephrotoxicity of the MA on rat renal papilla. [19] Bach et al reported that the analgesic efficacy was increased while using analgesics like PA and MA with coformulation of CAF. [20] Normally, in this combination, low concentration of MA present along with high concentrations of PA. [17] Thus, it is essential to determine trace level of MA in the presence of high concentration of PA and CAF.…”