Diallyl disulfide ameliorates methotrexate-induced nephropathy in rats: Molecular studies and network pharmacology analysis.

  title={Diallyl disulfide ameliorates methotrexate-induced nephropathy in rats: Molecular studies and network pharmacology analysis.},
  author={Emad H M Hassanein and Wafaa R. Mohamed and Marwa M. Khalaf and Abdel-Gawad S. Shalkami and Ahmed M. Sayed and Ramadan A. M. Hemeida},
  journal={Journal of food biochemistry},
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… 
1 Citations
Biological Functions of Diallyl Disulfide, a Garlic-Derived Natural Organic Sulfur Compound
This review systematically evaluated the biological functions of DADS and discussed the underlying molecular mechanisms of these functions, hoping that this review provides guidance and insight into the current literature and enables future research and the development of D ADS for intervention and treatment of multiple diseases.


Diallyl disulfide attenuates acetaminophen-induced renal injury in rats
The results suggest that DADS prevents AAP-induced acute nephrotoxicity, and that KIM-1 and NGAL may be useful biomarkers for the detection and monitoring of acute kidney injury associated with AAP exposure.
Renoprotective effects of umbelliferone on methotrexate-induced renal injury through regulation of Nrf-2/Keap-1, P38MAPK/NF-κB, and apoptosis signaling pathways.
UMB possess marked renoprotective effects against MTX-induced renal damage through modulating oxidative stress, inflammation and apoptosis with enhancement of its cytotoxic activity.
Protective effects of diallyl disulfide against acetaminophen-induced nephrotoxicity: A possible role of CYP2E1 and NF-κB.
  • Je-Won Ko, Jin-young Shin, +8 authors Jong-Choon Kim
  • Chemistry, Medicine
    Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
  • 2017
Results indicated that DADS could prevent AAP-induced nephrotoxicity, and might be due to its ability to decrease metabolic activation of AAP by inhibiting CYP2E1 and its potent antioxidant, antiapoptotic, and antiinflammatory effects via inhibition of NF-κB.
Rebamipide potentially mitigates methotrexate‐induced nephrotoxicity via inhibition of oxidative stress and inflammation: A molecular and histochemical study
Rebamipide treatment attenuated the reduction in glomerular size, the widening of the capsular spaces, and the tubular cell damage due to MTX administration, indicating the potential of REB as adjuvant therapy to prevent nephrotoxicity in patients receiving MTX treatment.
Renoprotective effects of montelukast, a cysteinyl leukotriene receptor antagonist, against methotrexate-induced kidney damage in rats
Montelukast significantly reduced the toxic effects of MTX as indicted from normalization of kidney-specific parameters, oxidative stress, and inflammatory mediators.
Neutrophil Infiltration and Oxidative Stress May Play a Critical Role in Methotrexate-Induced Renal Damage
Evidence is provided for the role of neutrophil infiltration and oxidative stress in MTX-induced renal damage and administration of inhibitors of myeloperoxidase or scavenging hypochlorous acid by supplementation with antioxidants as an adjuvant therapy may be promising in alleviating the renal side effect of MTX.
Formononetin Upregulates Nrf2/HO-1 Signaling and Prevents Oxidative Stress, Inflammation, and Kidney Injury in Methotrexate-Induced Rats
FN prevents MTX-induced AKI by activating Nrf2/HO-1 signaling and attenuates oxidative damage and inflammation and may represent an effective adjuvant that can prevent MTX nephrotoxicity, pending further mechanistic studies.
Commiphora molmol protects against methotrexate-induced nephrotoxicity by up-regulating Nrf2/ARE/HO-1 signaling.
In conclusion, C. molmol resin provided protection against MTX-induced AKI via activation of Nrf2 signaling and mitigation of oxidative stress.
Protective effect of pentoxyfilline in renal toxicity after methotrexate administration.
The increased level of tissue MDA and serum TNF-alpha level together may be suggested that the underlying mechanism is related to direct toxicity of MTX rather than blockage in folate synthesis in kidneys.
Mitochondrial dysfunction and oxidative stress are involved in the mechanism of methotrexate-induced renal injury and electrolytes imbalance.
A role for mitochondrial dysfunction and oxidative stress in the mechanism of MTX nephrotoxicity is suggested.