The Effects of Pomegranate and Carvacrol on Methotrexate-Induced Bone Marrow Toxicity in Rats

Abstract

Purpose: The aim of this study was to evaluate the effects of pomegranate (PMG) extract and carvacrol (CARV) on methotrexate (MTX)-induced oxidative stress and bone marrow toxicity. Methods: Wistar albino rats (32 rats) were divided into four groups (n=8): Group 1 was control; Group 2 was given a single intraperitoneal injection of methotrexate (20 mg/kg); Group 3 was treated with carvacrol (73 mg/kg i.p.) one day before MTX (20 mg/kg i.p.) injection; and, Group 4 received a single dose of MTX (20 mg/kg i.p) while PMG was administered orally for seven days at 225 mg/kg. After animals were euthanized, blood samples were taken to evaluate hematological parameters and oxidative stress. In addition, the femur was cropped and bone marrow was extracted for examination. Results: White blood cell count, hemoglobin, hematocrit and platelet count were found to be decreased in the MTX group, but these changes were prevented in the groups that received CARV and PMG. Furthermore, decreased bone marrow cellularity was found in the groups treated with MTX, whereas the PMG and CARV groups had cellularity similar to controls. Strikingly, oxidative stress increased in the MTX group, but was ultimately decreased in the rats that received the antioxidants PMG and CARV. Conclusion: Carvacrol and PMG were found to be protective against methotrexate-induced oxidative bone marrow damage. Use of these antioxidants, in combination with chemotherapeutics, may help to reduce some adverse effects of methotrexate.

Pomegranate-specific natural compounds as onco-preventive and onco-therapeutic compounds: Comparison with conventional drugs acting on the same molecular mechanisms

“…Methotrexate administration resulted in substantial increases in the levels of malondialdehyde, total oxidant status, and the oxidative stress index in both the serum and the lungs of the rats. On the other hand, pretreatment with PFE was able to counteract these effects [ 208 ].…”

Efficacy and Safety of Pomegranate Medicinal Products for Cancer

“…In adult Wistar rats, pomegranate juice augmented the antioxidant defence mechanism against carbon tetrachloride-induced reproductive toxicity [ 52 ]. In other tests, pomegranate extract was found to be protective against methotrexate-induced oxidative bone marrow damage [ 53 ], reduced methotrexate-induced neurotoxicity [ 54 ], and reversed methotrexate-induced oxidative stress and apoptosis in hepatocytes by modulating Nrf2-NF- κ B pathways in male Swiss albino rats. Preparations of pomegranate may, thus, help to reduce some adverse effects of methotrexate.…”