Molecular effects of nimesulide and aspirin on caspase-3, PPAR-α, and COX-2 gene expression in mice

The characterization of NSAIDs in reducing pain, inflammation, and fever by inhibiting cyclooxygenase (COX) leads to the inhibition of prostaglandin synthesis, which is the primary mechanism; still, there are other mechanisms of NSAIDs to produce these effects. In this study, we report a comparison between nimesulide (NIM) (selective COX-2) and aspirin (ASP) (non-selective COX-2) inhibitors in mice model at the molecular level on the caspase-3, peroxisome proliferation-activated receptors-alpha (PPAR-α) and gene expression of COX-2. Individual ED100 doses of NIM and ASP (15.8 and 424.5 mg/kg, i.m.) were injected in mice for 5 consecutive days with and without acetic acid. This study reports new pharmacological mechanisms for NIM and ASP to contribute as anti-inflammatory drugs by other important intracellular mechanisms. NIM outperforms ASP for caspase-3 inhibition in the kidney, liver, and plasma (anti-apoptotic and anti-inflammatory effects). Also, NIM was better than ASP in molecular effects at the PPAR-α reducing inflammation and producing its antinociceptive effects. NIM and ASP in therapeutic doses reduced the COX-2 gene expression in the kidney (down-regulation), which causes the potentiation effect as an anti-inflammatory and analgesic drug. This research provided that NIM outperforms ASP in efficacy for the new mechanisms of NIM and ASP for inhibition of caspase-3 and binding with PPAR-α which worked as an anti-inflammatory action and reduced pain plus the suppression of COX-2 gene expression (down-regulation), which all contributing to reducing inflammation, pain and fever.