TurkeyCarvacrol prevents methotrexateinduced renal oxidative injury and renal damage in rats
AbstractPurpose: e purpose of this study was to investigate the e ect of carvacrol (CAR) on methotrexate (MTX)-induced renal damage in rats.Methods: Twenty-four male rats were equally divided into three groups: group I, control treatment; group II, MTX-treated; and group III, MTX+CAR-treated. A single dose of CAR (73 mg/kg) was administered intraperitoneally to group III on the rst day of the experiment and a single dose of MTX (20 mg/kg) was administered intraperitoneally to groups II and III on the second day of the experiment. Blood samples and kidney tissue were obtained from each animal on day 8 for the measurement of malondialdehyde (MDA), total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI). Light microscopy was used for histopathological examination of kidney specimens.Results: MDA, TOS and OSI levels were signi cantly greater in the group receiving MTX alone relative to the control animals, while the TAS level was signi cantly reduced in the MTX group compared with the control group. e administration of CAR was associated with signi cantly decreased MDA, TOS, and OSI levels and increased TAS levels relative to the rats treated with MTX alone. Animals treated with CAR exhibited decreased tubular degeneration and architectural impairment relative to animals treated with MTX alone; however, the di erence in histological scores did not meet the threshold of statistical signi cance. e folic acid antagonist methotrexate (MTX) is used clinically to inhibit the synthesis of purines and pyrimidines [1]. MTX is commonly used at high doses to limit the growth of malignancies, but may also be used at low doses in in ammatory diseases, including psoriasis and rheumatoid arthritis, to inhibit the proliferation of in ammatory leukocytes [2][3][4]. MTX remains an essential component of modern clinical therapy for acute lymphoblastic leukemia and is the primary treatment for malignant gestational trophoblastic disease [5]. In addition to anti-proliferative activity, MTX has antiin ammatory and immunomodulatory properties; however, cytotoxic e ects and other side e ects limit the e cacy of MTX as an anti-in ammatory. Signi cant side e ects of MTX have been described in several organ systems. In particular, MTX has a detrimental e ect on kidney function [6]; however, the mechanism of MTX-induced toxicity remains unclear. More than 90% of MTX is ltered by the kidneys [7] and MTX treatment is known to cause renal failure at high doses [8]. Renal impairment can result in altered metabolism of MTX, delayed drug excretion and, subsequently, systemic toxicity. e toxic e ects of MTX are typically treated through hydration and alkalinization of the patient; however, these methods are insu cient to prevent all instances of MTX toxicity. Reactive oxygen species (ROS) have been implicated in the pathogenesis of MTX-induced renal damage [9,10]. MTX produces free oxygen radicals, resulting in enhanced li...