Inductive effect of Zoletil on cystathionine β-synthase expression in the rat brain

Zoletil is an anesthetic and immobilizing drug that has been used in the veterinary field for over 50 years; however, the effect of Zoletil, or its constituents, on brain cystathionine β-synthase (CBS) remains unknown. Here, we aimed to determine the effect of Zoletil on rat brain CBS by administering a single intraperitoneal injection of the drug and examining hydrogen sulfide (H₂S) and CBS levels in the cerebral cortex, hippocampus, and thalamus following three distinct behavioral phenotypes associated with the sedation procedure (e.g., loss of the righting reflex, return of the righting reflex, and return of walking). Zoletil administration resulted in significant decreases of endogenous H₂S in the cerebral cortex, hippocampus, and thalamus, and H₂S was observed to increase in these brain regions when rats recovered from the anesthesia. Quantitative real-time polymerase chain reaction, western blot, and immunohistochemistry revealed that CBS expression in the cerebral cortex and hippocampus exhibited the same trend as endogenous H₂S following Zoletil administration. In summary, our results demonstrated that Zoletil induced the expression of CBS which could exert region-specific regulation of H₂S in the cerebral cortex and hippocampus.