Diallyl sulfide protects against N -nitrosodiethylamineinduced liver tumorigenesis: Role of aldose reductase

Ibrahim, Safinaz S.; Nassar, Noha N.

doi:10.3748/wjg.14.6145

Cited by 33 publications

(24 citation statements)

References 55 publications

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“…Scuric et al [83] found a significantly increased AR mRNA levels in the livers of hepatocellular cancer patients compared to normal liver. Together, these observations strongly suggest that AR is overexpressed during oxidative stress– induced hepatocarcinogenesis [86]. In this context, various reports show the use of antioxidants against inflammation/ROS -induced hepatocarcinogeneis.…”

Section: Role Of Ar In Carcinogenesismentioning

confidence: 97%

Targeting Aldose Reductase for the Treatment of Cancer

Tammali

Srivastava²,

Ramana³

2011

CCDT

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It is strongly established by numerous studies that oxidative stress-induced inflammation is one of the major causative agents in a variety of cancers. Various factors such as bacterial, viral, parasitic infections, chemical irritants, carcinogens are involved in the initiation of oxidative stress-mediated inflammation. Chronic and persistent inflammation promotes the formation of cancerous tumors. Recent investigations strongly suggest that aldose reductase [AR; AKR1B1], a member of aldo-keto reductase superfamily of proteins, is the mediator of inflammatory signals induced by growth factors, cytokines, chemokines, carcinogens etc. Further, AR reduced product(s) of lipid derived aldehydes and their metabolites such as glutathionyl 1,4-dihydroxynonanol (GS-DHN) have been shown to be involved in the activation of transcription factors such as NF-κB and AP-1 which transcribe the genes of inflammatory cytokines. The increased inflammatory cytokines and growth factors promote cell proliferation, a main feature involved in the tumorigenesis process. Inhibition of AR has been shown to prevent cancer cell growth in vitro and in vivo models. In this review, we have described the possible association between AR with oxidative stress- and inflammation- initiated carcinogenesis. A thorough understanding of the role of AR in the inflammation – associated cancers could lead to the use of AR inhibitors as novel chemotherapeutic agents against cancer.

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Section: Role Of Ar In Carcinogenesismentioning

confidence: 97%

Targeting Aldose Reductase for the Treatment of Cancer

Tammali

Srivastava²,

Ramana³

2011

CCDT

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“…3B). For instance, protective effects of DAS treatment were observed in N-nitrosodiethylamine (NDEA)-induced liver tumorigenesis [36]. While NDEA treatment compromised several indices of liver function, DAS treatment normalized all non-enzymatic and enzymatic liver functions affected by NDEA.…”

Section: Protective Effects Of Dasmentioning

confidence: 99%

Diallyl Sulfide: Potential Use in Novel Therapeutic Interventions in Alcohol, Drugs, and Disease Mediated Cellular Toxicity by Targeting Cytochrome P450 2E1

Rao¹,

Midde²,

Miller³

et al. 2015

CDM

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Diallyl sulfide (DAS) and other organosulfur compounds are chief constituents of garlic. These compounds have many health benefits, as they are very efficient in detoxifying natural agents. Therefore, these compounds may be useful for prevention/treatment of cancers. However, DAS has shown appreciable allergic reactions and toxicity, as they can also affect normal cells. Thus their use as in the prevention and treatment of cancer is limited. DAS is a selective inhibitor of cytochrome P450 2E1 (CYP2E1), which is known to metabolize many xenobiotics including alcohol and analgesic drugs in the liver. CYP2E1-mediated alcohol/drug metabolism produce reactive oxygen species and reactive metabolites, which damage DNA, protein, and lipid membranes, subsequently causing liver damage. Several groups have shown that DAS is not only capable of inhibiting alcohol- and drug-mediated cellular toxicities, but also HIV protein- and diabetes-mediated toxicities by selectively inhibiting CYP2E1 in various cell types. However, due to known DAS toxicities, its use as a treatment modality for alcohol/drug- and HIV/diabetes-mediated toxicity have only limited clinical relevance. Therefore, effort is being made to generate DAS analogs, which are potent and selective inhibitor of CYP2E1 and poor substrate of CYP2E1. This review summarizes current advances in the field of DAS, its anticancer properties, role as a CYP2E1 inhibitor, preventing agent of cellular toxicities from alcohol, analgesic drugs, xenobiotics, as well as, from diseases like HIV and diabetes. Finally, this review also provides insights toward developing novel DAS analogues for chemical intervention of many disease conditions by targeting CYP2E1 enzyme.

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“…Thus, a decreased A/G ratio often indicates the presence of impaired liver function (Ibrahim et al, 2008). DENA significantly decreased total protein, albumin, and A/G levels, which indicated poor liver function and inability to fight infections.…”

Section: Discussionmentioning

confidence: 99%