| DOI: 10.29090/psa.2025.03.25.4795 | Pharm Sci Asia 2025; 52(3), 417-426 |
Piroxicam attenuates oxidative stress in glucolipotoxic C2C12 myotubes and protein glycation damage: Models relevant to T2DM pathophysiologyLiezl Mae Lozano1,2*, Heisen Jane Esdicul1, Quisha Jessen Leyrita1, Charlie Lavilla Jr.1
1 Mindanao State University - Iligan Institute of Technology, Iligan City, Philippines
2
North Eastern Mindanao State University - Lianga Campus.
Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance and associated oxidative and glycative stress, contributing to disease progression and complications. Non-steroidal anti-inflammatory drugs (NSAIDs) such as piroxicam (PIR) and naproxen (NAP) have shown potential repurposable antidiabetic effects, partly through inhibition of dipeptidyl peptidase-4 (DPP-4), an enzyme regulating glucose metabolism. This study evaluated PIR and NAP (10 μM) in a glucolipotoxic (GLT) cellular model of insulin resistance. C2C12 mouse myotubes were incubated in standard tissue culture media, or media supplemented with 28 mM glucose, 200 μM palmitic acid, and 200 μM oleic acid as a cellular model of diabetic glucolipotoxicity. GLT conditions elevated intracellular reactive oxygen species (ROS) by 73.5% ± 9.4% (p < 0.05). Both NAP and PIR significantly reduced ROS levels by 87.0% ± 14.6% and 74.1% ± 9.9%, respectively (p < 0.05). PIR (10 μM) was prioritized for further assessment for effects on glucose uptake in the same model where it enhanced glucose uptake by 191.7% ± 98.6% (p < 0.05). Subsequently, PIR’s biochemical activities (40 ppm) were evaluated in cell-free assays. PIR significantly inhibited AGE formation in the BSA-methylglyoxal model, reducing fluorescence by 245.4% ± 36.3% at day 7 and 145.2% ± 29.2% at day 14 (p < 0.001). It showed a protective trend against amyloid fibril formation, decreasing Congo red absorbance by 55.0% ± 3.8%, although this effect was not statistically significant (p < 0.005). Pancreatic lipase inhibition was limited (~12%, p < 0.05), indicating a lack of anti-obesity potential at tested concentrations. While PIR shows promising antioxidative and antiglycation effects, further studies are needed to fully elucidate its clinical relevance in T2DM management.
Keyword:
Type 2 diabetes; Non-steroidal anti-inflammatory drugs; Glucolipotoxicity; Reactive species scavenging; Anti-glycation
Download full paper (PDF File size: 752.33 KB.)
|
