title: Protective effect of topical application of α-tocopherol and/or N-acetyl cysteine on argemone oil/alkaloid-induced skin tumorigenesis in mice.
abstract: Since bioantioxidants in plasma of Epidemic Dropsy patients [a condition caused by consumption of adulterated mustard oil with argemone oil (AO)] were found to be significantly decreased, the beneficial effect of N-acetyl cysteine (NAC) and α-tocopherol (TOCO) against AO- or sanguinarine (SANG)-induced tumorigenicity was undertaken in mice. Topical application of TOCO and NAC either alone or in combination showed significant protection against AO/TPA- and SANG/TPA-induced skin tumorigenicity. Histopathological findings suggest that papillomatous growth in AO/TPA- and SANG/TPA-treated animals were substantially protected following topical application of TOCO or NAC. Further, treatment of TOCO and NAC either alone or in combination to AO/TPA- or SANG/TPA-induced mice significantly decreased lipid peroxidation, along with significant revival in glutathione (GSH) content and activities of tyrosinase, histidase, catalase, SOD, GSH peroxidase, and GSH reductase in skin. In vitro studies showed that TOCO and/or NAC significantly decreased the AO and SANG induced cell proliferation and activation of ERK, p38, JNK MAPKs and NF-κB signaling in HaCaT cells. In summary, TOCO and NAC may be useful in preventing the tumorigenic response of AO and SANG probably by acting as scavenger of free radicals and inhibiting MAPKs and NF-κB signaling.
authors.affiliation: Food, Drug and Chemical Toxicology Group, CSIR-Indian Institute of Toxicology Research, Uttar Pradesh, India.
authors.forename: Anu
authors.initials: A
authors.lastname: Pal
authors.forename: Shamshad
authors.initials: S
authors.lastname: Alam
authors.forename: Jaya
authors.initials: J
authors.lastname: Singhal
authors.forename: Rahul
authors.initials: R
authors.lastname: Kumar
authors.forename: Kausar M
authors.initials: KM
authors.lastname: Ansari
authors.forename: Mukul
authors.initials: M
authors.lastname: Das
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D053119:Benzophenanthridines / Q000009:adverse effects; D063646:Carcinogenesis / Q000139:chemically induced / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D005978:Glutathione / Q000032:analysis / Q000378:metabolism; D006801:Humans; D007546:Isoquinolines / Q000009:adverse effects; D015227:Lipid Peroxidation / Q000187:drug effects; D020935:MAP Kinase Signaling System; D051379:Mice; D009149:Mustard Plant / Q000009:adverse effects*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D010938:Plant Oils / Q000009:adverse effects*; D012867:Skin / Q000187:drug effects / Q000473:pathology; D024502:alpha-Tocopherol / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D000975:Antioxidants; D053119:Benzophenanthridines; D007546:Isoquinolines; D016328:NF-kappa B; D010938:Plant Oils; C030610:argemone oil; C005705:sanguinarine; D048051:p38 Mitogen-Activated Protein Kinases; D005978:Glutathione; D024502:alpha-Tocopherol; C027793:mustard oil; D000111:Acetylcysteine