Abstract
Methotrexate (MTX) is an antiproliferative drug used widely in chemotherapy, rheumatoid arthritis, and other autoimmune diseases. Despite this, its long-term administration causes testicular adverse effects. Carvacrol is a phytochemical derived from aromatic plants of the genera Oregano. It is known to have anti-inflammatory and anti-oxidant effects and to inhibit the growth of a variety of cancer cells. The present study was designed to evaluate the antioxidant effect of carvacrol on MTX-induced testicular damage. Twenty-four adult rats were randomly divided into four groups, six rats each, as follows: Control, Carvacrol (40mg/kg b.w. daily orally), MTX (25 mg/kg b.w single shot I/P) and Carvacrol and MTX. Testicular biomarkers, redox status and Nrf2 gene expression tests were assessed after 15 days. MTX caused alterations in testosterone hormone and total and prostatic acid phosphatases. Furthermore, testicular 8-OHdG and MDA were increased while reduced GSH was decreased indicating testicular oxidative damage. Concomitant administration of carvacrol was able to restore the adverse effects of MTX. This was observed in the revised levels of the mentioned parameters nearly to normal in comparison to the control and MTX groups. In the present study, we report that carvacrol ameliorates MTX-induced testicular damage by protection from oxidative stress, decrease in DNA damage, and enhancement of serum testicular biomarkers.

Key words: Carvacrol, Methotrexate, Testis, Oxidative stress