Neuroprotective effects of carvacrol and pomegranate against methotrexate-induced toxicity in rats

F. Celik, C. Gocmez, M. Bozkurt, I. Kaplan, K. Kamasak, E. Akil, E. Dogan, A. Guzel, E. Uzar

Department of Anesthesiology, Department of Neurosurgery, Department of Physical Medicine and Rehabilitation, Department of Biochemistry, Department of Neurology, Dicle University,
Diyarbakir, Turkey. drfeyzicelik@gmail.com

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• Pharmacology

BACKGROUND: Studies related to the use of various antioxidant and anti-inflammatory drugs to decrease the toxic side effects related to MTX have been carried out. However, since no medicine providing full protection against the side effects of MTX has been discovered, the discovery of new agents is required.

AIM: The aim of this study was to determine whether methotrexate (MTX) causes oxidative stress and an inflammatory response in sciatic nerve, as well as whether carvacrol (CAR) and pomegranate (POM) have protective effects against the resulting oxidative stress and inflammatory response.

MATERIALS AND METHODS: 32 adult male Wistar albino rats were used in the study. The animals were divided into 4 groups: Group C: the rats were not given any medication; Group MTX: On study day 2, the rats were given a single dose of 20 mg/kg MTX, administered intraperitoneally; Group MTX+CAR: On study day one, the rats were administered a single dose of 73 mg/kg CAR intraperitoneally. On study day two, a single dose of 20 mg/kg MTX was administered intraperitoneally; Group MTX+POM: For seven days starting from the study day one, rats were given 225 mg/kg POM extract once a day through orogastric gavage. On study day two, a single dose of 20 mg/kg MTX was administered intraperitoneally. All animals were sacrificed on the day eight. TOS, TAS, MDA, TNF-α and IL-1β levels were evaluated in the sciatic nerve tissue.

RESULTS: In comparison to the control group, a decrease in TAS levels and an increase in TOS, MDA, IL-1β and TNF-α levels were detected in the MTX group. Compared to the MTX group, the MTX+CAR group had a significant increase in TAS level and significant decreases in TOS, MDA, IL-1β and TNF-α levels. In comparison to the MTX group, the MTX+POM group had a significant decrease in MDA, IL-1β and TNF-α levels. When the MTX+CAR and MTX+POM groups were compared, the TNF-α level measured was lower in the MTX+CAR group.

CONCLUSIONS: In this work, we have shown that MTX causes a significant oxidative stress and inflammatory response in rats’ sciatic nerve tissue and that CAR had an antioxidant effect in this system. Furthermore, we have proven, for the first time, that both CAR and POM decreased the pro-inflammatory response.

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