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. 2015 Jul;28(3):165-70.
doi: 10.1293/tox.2015-0016. Epub 2015 May 24.

Histopathology and oxidative stress analysis of concomitant misoprostol and celecoxib administration

Derek E Murrell  1 , James W Denham  2 , Sam Harirforoosh  1
Affiliations

Histopathology and oxidative stress analysis of concomitant misoprostol and celecoxib administration

Derek E Murrell et al. J Toxicol Pathol. 2015 Jul.

Erratum in

  • Errata (Printer's correction).
    [No authors listed] [No authors listed] J Toxicol Pathol. 2016 Jan;29(1):74. Epub 2016 Feb 17. J Toxicol Pathol. 2016. PMID: 26989306 Free PMC article.

Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs), non-selective or selective inhibitors of cyclooxygenase (COX-1 and -2), reduce pain and inflammation associated with arthritic diseases. Celecoxib, a COX-2-selective inhibitor providing decreased gastric injury relative to non-selective NSAIDs, is commonly prescribed. Misoprostol, a prostaglandin analog, supplements NSAID-inhibited prostaglandin levels. As concomitant celecoxib and misoprostol administration has been shown to intensify renal adverse effects, this article examined the influence of concomitant administration on hepatic histopathology, oxidative stress, and celecoxib concentration. On days 1 and 2, rat groups (n = 6) were gavaged twice daily (two groups with vehicle and two groups with 100 μg/kg misoprostol). From day 3 to day 9, one celecoxib dose (40 mg/kg) replaced a vehicle dose of one group and one group received celecoxib in addition to misoprostol. Livers were harvested on day 10. No hepatic abnormalities were observed denoting a lack of influence by either drug. Also no change in mean biomarker levels was detected. The changes in hepatic celecoxib concentration in the misoprostol-receiving group compared to control were not significant. Thus misoprostol does not influence hepatic celecoxib effects in terms of histopathology, oxidative stress, or celecoxib concentration level at the dosage and duration examined.

Keywords: NSAIDs; celecoxib; glutathione; histopathology; malondialdehyde; misoprostol.

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Figures

Fig. 1.
Fig. 1.
Liver histopathology. Liver cross sections (H&E stained) from rat groups treated with (A) vehicle+vehicle, (B) vehicle+celecoxib, (C) misoprostol+misoprostol, and (D) misoprostol+celecoxib. 10× magnification with 40× insets
Fig. 2.
Fig. 2.
Hepatic GSH concentration. Effect of control (VEH+VEH), vehicle+celecoxib (VEH+CEL), misoprostol+misoprostol (MISO+MISO), or misoprostol+celecoxib (MISO+CEL) on hepatic GSH concentration. The values were not significantly different (p>0.05).
Fig. 3.
Fig. 3.
Hepatic MDA concentration. Effect of control (VEH+VEH), vehicle+celecoxib (VEH+CEL), misoprostol+misoprostol (MISO+MISO), or misoprostol+celecoxib (MISO+CEL) treatment on hepatic MDA concentration. The values were not significantly different (p>0.05).
See this image and copyright information in PMC

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