Carvacrol prevents methotrexate-induced renal oxidative injury and renal damage in rats

Abstract

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...

Quercetin ameliorates methotrexate-induced renal damage, apoptosis and oxidative stress in rats

“…dose of 20 mg/kg as previously described in certain tissue toxicity studies. 11,25 Although the exact mechanisms of MTX-associated nephrotoxicity have not been clearly understood, recent studies suggest that it may be due to oxidative stress. 26 QE is a very potent anti-oxidant providing protection against oxidative injury through prevention of the formation of hydroxyl radicals via Fe and Cu.…”

“…Dosage of MTX was determined from those described by relevant literatures. [11][12][13] The dose of QE was decided based on a recent study reported by Aktoz et al 14…”

“…9 Agents with potent anti-oxidant effects have been tested in terms of their efficacy to prevent MTX-related side effects, with significant success in some of these studies. 10,11 However, the results of these studies with these agents have not been adequately reflected in the clinical studies due a number of factors such as the high cost of such chemicals or absence of licensed preparations.…”

Effects of Lycopene Alone or Combined with Melatonin on Methotrexate-Induced Nephrotoxicity in Rats

“…with a single dose of 20 mg/kg of Mtx (Avadi et al, 2011;Bozkurt et al, 2014) and given corn oil by oral gavage (o.g).…”

Tetramethylpyrazine identified by a network pharmacology approach ameliorates methotrexate-induced oxidative organ injury

“…Toxicity from oxidative injury was recently shown to be prevented or alleviated by herbal compounds with antioxidative activity (Dalaklioglu et al, 2013;Bozkurt et al, 2014;Ali et al, 2014). Resveratrol may have a protective effect against MTX-induced hepatotoxicity by blocking oxidative stress-mediated lipid peroxidation (Dalaklioglu et al, 2013).…”