Effects of diclofenac exposure on myelin organization, autophagy, and cellular proliferation in the rat cerebral cortex and hippocampus

Diclofenac, an over-the-counter nonsteroidal anti-inflammatory drug (NSAID) among others, has still not been fully characterized regarding its potential neurotoxic effects on brain tissue. The present research aimed to assess the influence of frequent diclofenac administration on myelin preservation, autophagy-related cellular responses, and cell proliferation in the cortex and hippocampus of the rat brain. Twelve male Wistar albino rats were randomly allocated into Control (n = 6) and Diclofenac (n = 6) groups. Diclofenac sodium (7.5 mg/kg) was administered orally twice daily for five consecutive days. Brain tissues were stained with Klüver–Barrera to assess myelin loss and further processed for immunohistochemistry of autophagy markers (Beclin-1, LC3, p62) and PCNA. Diclofenac exposure resulted in significant demyelination not only in the cerebral cortex but also in the hippocampus, and, at the same time, altered the organization of hippocampal neurons. Beclin-1 and LC3 immunoreactivity showed a notable increase in both areas, and p62 increased specifically in the cerebral cortex, while there was a significant decrease in the PCNA immunoreactivity in both areas. To sum up, the consecutive administration of diclofenac causes demyelination, alters autophagy signaling, and inhibits cell proliferation in rat brain tissue, suggesting a possible mechanism for diclofenac's neurotoxic effects in the animal model.