Ketoprofen-Induced Cyclooxygenase Inhibition in Renal Medulla and Platelets of Rats Treated with Caffeine

Abstract

It has been suggested that caffeine can augment analgesic activity and aggravate side effects of nonsteroidal anti-inflammatory drugs (NSAIDs). The aim of the present study was to investigate a possible interaction between ketoprofen and caffeine on prostaglandin (PG) biosynthesis and cyclooxygenase (COX) mRNA expression in the rat renal medulla ex vivo. Treatment of rats with ketoprofen (60 min before) resulted in a dose-dependent (estimated ID₅₀ 0.3 mg/kg p.o.) reduction of PGE₂ biosynthesis in renal medulla ex vivo. Ketoprofen (0.3 mg/kg)-induced inhibition of PGE₂ biosynthesis was stable between 30 and 180 min and still detectable 300 min after drug administration. Caffeine (10 mg/kg) did not cause a detectable effect on its own, nor did it significantly affect ketoprofen-induced inhibition of renal medullary PGE₂ biosynthesis. Similar results were obtained with repeated daily drug administration for 1 week: there was no significant effect of caffeine on ketoprofen-induced inhibition of renal medullary PGE₂ biosynthesis. The absence of significant caffeine effects on ketoprofen-induced inhibition of renal medullary PGE₂ biosynthesis was paralleled by experiments showing no significant effect of caffeine on ketoprofen-induced inhibition of platelet thromboxane (TX)B₂ biosynthesis. Additional experiments showed increased COX-2 mRNA expression in the renal medulla 60 min after ketoprofen administration, that was not significantly influenced by concomitant caffeine treatment. Treatment of rats with ketoprofen for 1 week had no significant effects on COX-2 mRNA expression. The present results show that ketoprofen caused inhibition of PGE₂ biosynthesis in the rat renal medulla ex vivo with a potency similar to that reported for in vivo models suggesting that the ex vivo approach is a valid model to test a possible interference of caffeine with ketoprofen-induced COX inhibition. The absence of detectable effects of caffeine on time course or magnitude of ketoprofen-induced suppression of PGE₂ biosynthesis in this model indicates, therefore, that possible adverse actions of co-administered caffeine on renal function are not related to interference with renal COX inhibition.

Anti-Platelet Aggregation and Anti-Cyclooxygenase Activities for a Range of Coffee Extracts (Coffea arabica)

“…Surprisingly, we found that inhibition was not influenced by CGA and CF when compared to the standard. Importantly, CF augmented the activity of NSAIDs such as aspirin, indomethacin and ketoprofen; nevertheless, it did not influence NSAIDs-induced inhibition of platelet thromboxanes (TXs) [39]. Likewise, there is increasing evidence that the consumption of phenolic-rich beverages has the potential to lower and prevent the risk of developing thrombosis.…”

Inhibition of Prostaglandin Biosynthesis in Human Endotoxin-Stimulated Peripheral Blood Monocytes: Effects of Caffeine

“…1]. It has been shown in several preparations that caffeine on its own does not inhibit tissue prostaglandin biosynthesis, nor does it augment inhibition exerted by COX inhibitors [e.g., [2][3][4]. However, results obtained in rat microglial cells suggest that adenosine A 2 receptor agonists can induce COX-2 mRNA and cause a concomitant increase in prostaglandin E 2 (PGE 2 ) biosynthesis [5]; in this preparation the nonselec-Ulcar/Schuligoi/Heinemann/Santner/ Amann tive adenosine receptor antagonist caffeine augmented the inhibitory effect of acetylsalicylic acid on endotoxininduced PGE 2 biosynthesis [6].…”

Effect of ketoprofen on immune cells in mice

“…Ketoprofen inhibits cycloxygenase COX and thereby inhibits prostaglandin synthesis [12]. Thus it produces anti-inflammatory, anti-pyretic and analgesic effects [13].…”