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Diallyl disulfide ameliorates methotrexate‐induced nephropathy in rats: Molecular studies and network pharmacology analysis
Author(s) -
Hassanein Emad H. M.,
Mohamed Wafaa R.,
Khalaf Marwa M.,
Shalkami AbdelGawad S.,
Sayed Ahmed M.,
Hemeida Ramadan A. M.
Publication year - 2021
Publication title -
journal of food biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.507
H-Index - 47
eISSN - 1745-4514
pISSN - 0145-8884
DOI - 10.1111/jfbc.13765
Subject(s) - diallyl disulfide , organosulfur compounds , nephropathy , chemistry , pharmacology , diallyl trisulfide , apoptosis , creatinine , glutathione , renal function , biochemistry , medicine , endocrinology , enzyme , sulfur , diabetes mellitus , organic chemistry
Methotrexate (MTX) is a promising chemotherapeutic agent. Its medical use is limited by induced nephropathy. Our study was designed to explore the reno‐protective effect of diallyl disulfide (DADS), an organosulfur compound of garlic oil, on MTX‐induced nephropathy. Adult rats were randomly divided into 4 groups; normal control, DADS (50 mg kg –1 day –1 , p.o.), MTX (20 mg/kg, i.p.) and DADS+MTX. DADS significantly decreased serum creatinine, urea, uric acid, and albumin levels with an improvement of final body weight. Additionally, DADS markedly attenuated MTX‐induced elevations in renal MDA and NO 2 ‐ contents with an increase in GSH content and SOD activity. Mechanistically, DADS effectively down‐regulated mRNA expression level of renal p38 and NF‐κB. Additionally, DADS positively regulated the NRF2 gene with a remarkable inhibition of Keap‐1 gene. Furthermore, DADS up‐regulated BCL2 protein and remarkably suppressed the expression of both BAX and caspase‐3 proteins. Overall, DADS has favorable renal protection against MTX‐induced nephropathy via modulation of Keap‐1/NRF2, p38/NF‐κB, and BCL2/BAX/caspase‐3 signaling. Practical applications Diallyl disulfide is one of the organosulfur compounds of garlic oil. Our study demonstrated that DADS substantially alleviated the decline of kidney function and renal injury induced by MTX. The antioxidative, anti‐inammatory, and anti‐apoptotic properties may constitute an important part of its therapeutic applications via regulation of p38/NF‐κB, Keap‐1/NRF2, and BCL2/BAX/caspase‐3 signaling pathways. Therefore, DADS could be a potential therapeutic adjunct in cancer chemotherapy to decrease the associated side effects of MTX. It should be further explored clinically as a protective agent for MTX‐treated cancer patients.