Diclofenac Disrupts the Circadian Clock and through Complex Cross-Talks Aggravates Immune-Mediated Liver Injury-A Repeated Dose Study in Minipigs for 28 Days.

The gene expression changes agreed with the lower serum cholesterol levels determined for diclofenac-treated animals; however, the results did not reach statistical significance.

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The reduced expression of porcine CYP monooxygenases is likely caused by hepatic inflammation in response to diclofenac treatment [ 69 , 70 ] and, given the highly significant increase in activated neutrophils (see above and Figure 6 ), we propose reactive metabolism to be primarily catalyzed by myeloperoxidase of neutrophils.

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