Melatonin and alpha lipoic acid attenuate methotrexate/ cisplatin-induced kidney toxicity in albino rats

Introduction: Most anticancer therapies are seldom effective by single anticancer drug due to biologic heterogeneity and multiple genetic alterations stimulating the use of anticancer drug combinations. Methotrexate/cisplatin (MTX/CPT) has shown beneficial effects in the treatment of metastatic and...

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Autores principales:	Elias Adikwu, Nelson Clement Ebinyo, Bonsome Bokolo
Formato:	article
Lenguaje:	EN
Publicado:	Society of Diabetic Nephropathy Prevention 2020
Materias:	anticancer antioxidants kidney toxicity protection melatonin alpha lipoic acid methotrexate cisplatin Therapeutics. Pharmacology RM1-950 Diseases of the genitourinary system. Urology RC870-923
Acceso en línea:	https://doaj.org/article/bf5de60b30da4d3a8124e6d629be943c
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spelling	oai:doaj.org-article:bf5de60b30da4d3a8124e6d629be943c2021-11-17T08:13:31ZMelatonin and alpha lipoic acid attenuate methotrexate/ cisplatin-induced kidney toxicity in albino rats2345-420210.34172/npj.2020.17https://doaj.org/article/bf5de60b30da4d3a8124e6d629be943c2020-05-01T00:00:00Zhttps://jnephropharmacology.com/PDF/npj-4298https://doaj.org/toc/2345-4202Introduction: Most anticancer therapies are seldom effective by single anticancer drug due to biologic heterogeneity and multiple genetic alterations stimulating the use of anticancer drug combinations. Methotrexate/cisplatin (MTX/CPT) has shown beneficial effects in the treatment of metastatic and malignant tumors, but its use may perturb kidney function. Objectives: The present study assessed the protective effects of melatonin (MT) and alpha-lipoic acid (ALA) against kidney toxicity induced by MTX/CPT in albino rats. Materials and Methods: Forty-eight adult male albino rats were randomized into groups and pretreated with MT (10 mg/kg), ALA (10 mg/kg) and MT+ALA daily for five days before treatment with 20 mg/kg of MTX and 5 mg/kg of CPT intraperitoneally on the fifth day. After overnight fast, rats were sacrificed, serum samples were centrifuged from blood samples and assessed for renal function parameters and electrolytes. Kidneys were assessed for oxidative stress (OS) markers and pathology. Results: Significant (P<0.001) increases in serum creatinine, urea, and uric acid levels with significant (P<0.001) decreases in total protein, albumin, potassium, sodium, chloride, and bicarbonate levels were obtained in MTX/CPT-intoxicated rats when compared to control. Furthermore, kidney malondialdehyde levels were significantly (P<0.001) increased whereas catalase, superoxide dismutase, glutathione and glutathione peroxidase levels were significantly (P<0.001) decreased in MTX/CPT-intoxicated rats when compared to control. Pathologic changes marked by atrophic glomeruli were detected in the kidneys of MTX/CPT-treated rats. However, nephrotoxicity observed in MTX/CPT-treated rats was significantly reversed in MT (P<0.01), ALA (P<0.05) and MT+ALA (P<0.001) pretreated rats when compared to MTX/CPT -treated rats. Conclusion: MT and ALA supplementations attenuate nephrotoxicity caused by MTX/CPT.Elias AdikwuNelson Clement EbinyoBonsome BokoloSociety of Diabetic Nephropathy Prevention articleanticancerantioxidantskidneytoxicityprotectionmelatoninalpha lipoic acidmethotrexatecisplatinTherapeutics. PharmacologyRM1-950Diseases of the genitourinary system. UrologyRC870-923ENJournal of Nephropharmacology, Vol 9, Iss 2, Pp e17-e17 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	anticancer antioxidants kidney toxicity protection melatonin alpha lipoic acid methotrexate cisplatin Therapeutics. Pharmacology RM1-950 Diseases of the genitourinary system. Urology RC870-923
spellingShingle	anticancer antioxidants kidney toxicity protection melatonin alpha lipoic acid methotrexate cisplatin Therapeutics. Pharmacology RM1-950 Diseases of the genitourinary system. Urology RC870-923 Elias Adikwu Nelson Clement Ebinyo Bonsome Bokolo Melatonin and alpha lipoic acid attenuate methotrexate/ cisplatin-induced kidney toxicity in albino rats
description	Introduction: Most anticancer therapies are seldom effective by single anticancer drug due to biologic heterogeneity and multiple genetic alterations stimulating the use of anticancer drug combinations. Methotrexate/cisplatin (MTX/CPT) has shown beneficial effects in the treatment of metastatic and malignant tumors, but its use may perturb kidney function. Objectives: The present study assessed the protective effects of melatonin (MT) and alpha-lipoic acid (ALA) against kidney toxicity induced by MTX/CPT in albino rats. Materials and Methods: Forty-eight adult male albino rats were randomized into groups and pretreated with MT (10 mg/kg), ALA (10 mg/kg) and MT+ALA daily for five days before treatment with 20 mg/kg of MTX and 5 mg/kg of CPT intraperitoneally on the fifth day. After overnight fast, rats were sacrificed, serum samples were centrifuged from blood samples and assessed for renal function parameters and electrolytes. Kidneys were assessed for oxidative stress (OS) markers and pathology. Results: Significant (P<0.001) increases in serum creatinine, urea, and uric acid levels with significant (P<0.001) decreases in total protein, albumin, potassium, sodium, chloride, and bicarbonate levels were obtained in MTX/CPT-intoxicated rats when compared to control. Furthermore, kidney malondialdehyde levels were significantly (P<0.001) increased whereas catalase, superoxide dismutase, glutathione and glutathione peroxidase levels were significantly (P<0.001) decreased in MTX/CPT-intoxicated rats when compared to control. Pathologic changes marked by atrophic glomeruli were detected in the kidneys of MTX/CPT-treated rats. However, nephrotoxicity observed in MTX/CPT-treated rats was significantly reversed in MT (P<0.01), ALA (P<0.05) and MT+ALA (P<0.001) pretreated rats when compared to MTX/CPT -treated rats. Conclusion: MT and ALA supplementations attenuate nephrotoxicity caused by MTX/CPT.
format	article
author	Elias Adikwu Nelson Clement Ebinyo Bonsome Bokolo
author_facet	Elias Adikwu Nelson Clement Ebinyo Bonsome Bokolo
author_sort	Elias Adikwu
title	Melatonin and alpha lipoic acid attenuate methotrexate/ cisplatin-induced kidney toxicity in albino rats
title_short	Melatonin and alpha lipoic acid attenuate methotrexate/ cisplatin-induced kidney toxicity in albino rats
title_full	Melatonin and alpha lipoic acid attenuate methotrexate/ cisplatin-induced kidney toxicity in albino rats
title_fullStr	Melatonin and alpha lipoic acid attenuate methotrexate/ cisplatin-induced kidney toxicity in albino rats
title_full_unstemmed	Melatonin and alpha lipoic acid attenuate methotrexate/ cisplatin-induced kidney toxicity in albino rats
title_sort	melatonin and alpha lipoic acid attenuate methotrexate/ cisplatin-induced kidney toxicity in albino rats
publisher	Society of Diabetic Nephropathy Prevention
publishDate	2020
url	https://doaj.org/article/bf5de60b30da4d3a8124e6d629be943c
work_keys_str_mv	AT eliasadikwu melatoninandalphalipoicacidattenuatemethotrexatecisplatininducedkidneytoxicityinalbinorats AT nelsonclementebinyo melatoninandalphalipoicacidattenuatemethotrexatecisplatininducedkidneytoxicityinalbinorats AT bonsomebokolo melatoninandalphalipoicacidattenuatemethotrexatecisplatininducedkidneytoxicityinalbinorats
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Melatonin and alpha lipoic acid attenuate methotrexate/ cisplatin-induced kidney toxicity in albino rats

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