Diclofenac attenuates inflammation through TLR4 pathway and improves exercise performance after exhaustive swimming

Background: The use of NSAIDs has become a common practice to counteract the pro-inflammatory acute effects of exercise, in order to improve sports performance. The liver, due to its central role in energy metabolism, may be involved primarily in the process of ROS generation and consequently inflammation after exhaustive exercise.

Objective: To analyze the influence of diclofenac on the liver TLR4 pathway and time to exhaustion in rats submitted to repeated exhaustive swimming.

Methods: An exhaustive test was performed in order to mimic athletes' routine, and inflammatory status and oxidative stress markers were evaluated in the liver. Animals were divided into sedentary and exhaustion groups, with this last performing three exhaustive swimming bouts. At the same time, diclofenac or saline was pre-administered once a day for nine days.

Results: Data showed significantly increased COX-2, TLR4, and MyD88 protein content in the liver after exhaustive swimming bouts. The levels of pro-inflammatory cytokines also increased after exhaustive exercise, while these effects were attenuated in the group treated with diclofenac plus exhaustive swimming bouts. The anti-inflammatory modulation provoked by diclofenac treatment was associated with an increased time to exhaustion in the exercise bouts. The exhaustive exercise increased TBARS formation, but diclofenac treatment blunted this elevation, while GSH/GSSG ratios in both exhaustion-saline and exhaustion-diclofenac-treated groups were lower than in the sedentary-saline group.

Conclusions: Our findings suggest that diclofenac may improve exercise performance and represent an effective tool to ameliorate the pro-inflammatory status in liver when associated with exhaustive exercise, and the liver may be a possible therapeutic target.