Abstract
Methotrexate is an antimetabolic drug with a myriad of serious side effects including nephrotoxicity, which presumably occurs due to oxidative tissue damage. Here, we evaluated the potential protective effect of lycopene, a potent antioxidant carotenoid, given in two different pharmaceutical forms in methotrexate-induced kidney damage in rats. Serum biochemical (urea and creatinine) and tissue oxidative damage markers and histopathological kidney changes were evaluated after systemic administration of both lycopene dissolved in corn oil and lycopene encapsulated in nanoliposomes. Similar to previous studies, single dose of methotrexate induced severe functional and morphological alterations of kidneys with cell desquamation, tubular vacuolation, and focal necrosis, which were followed by serum urea and creatinine increase and disturbances of tissue antioxidant status. Application of both forms of lycopene concomitantly with methotrexate ameliorated changes in serum urea and creatinine and oxidative damage markers and markedly reversed structural changes of kidney tissue. Moreover, animals that received lycopene in nanoliposome-encapsulated form showed higher degree of recovery than those treated with free lycopene form. The findings of this study indicate that treatment with nanoliposome-encapsulated lycopene comparing to lycopene in standard vehicle has an advantage as it more efficiently reduces methotrexate-induced kidney dysfunction.
Highlights
Methotrexate (MTX) is antimetabolic drug which is often used for the treatment of several autoimmune disorders such as rheumatoid arthritis, psoriasis, and various malignant tumors including lymphoblastic leukemia, lymphoma, osteosarcoma, breast cancer, and head and neck cancer [1]
Serum biochemical and tissue oxidative damage markers and histopathological kidney changes were evaluated after systemic administration of both lycopene dissolved in corn oil and lycopene encapsulated in nanoliposomes
Since the lycopene has the ability to quench singlet oxygen, which is related to its double bonds in molecule and the opening of the β-ionone ring, we examined and compared antioxidant activity of both free and encapsulated lycopene in in vitro oxidative damage model
Summary
Methotrexate (MTX) is antimetabolic drug which is often used for the treatment of several autoimmune disorders such as rheumatoid arthritis, psoriasis, and various malignant tumors including lymphoblastic leukemia, lymphoma, osteosarcoma, breast cancer, and head and neck cancer [1]. Similar to other agents with nephrotoxic effect, MTX-induced renal impairment is clinically followed by hematuria and increased levels of serum creatinine and urea in humans. These effects can be faithfully reproduced in experimental animals after single dose of MTX [4, 5]. Spreng fruit, papayas, etc.), possesses a strong antioxidant activity It protects cells against damage caused by free radicals with its reactive oxygen species (ROS) scavenging properties [6, 7]. To the best of our knowledge, no study exists which shows potential of using lycopene in this new pharmaceutical formulation to treat drug-induced tissue injury, we aimed at evaluating characteristics of the nanoliposome encapsulation and efficacy of this preparation in preventing/ameliorating methotrexate-induced kidney injury.
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