Effect of Onosma echioides on DMBA/croton oil mediated carcinogenic response, hyperproliferation and oxidative damage in murine skin.
The current study unveils the effect of O. echioides extract on two-stage skin carcinogenesis and on tumor promoter induced markers and oxidative stress in Swiss mice. Treatment of dorsal shaven cutaneous portions of the mice with single topical application of benzoyl peroxide (BPO) followed by exposure to ultraviolet B (UVB) radiation induced significant oxidative stress and elevated the marker parameters of tumor promotion. Similar effects were observed with 12-O-tetradecanoyl phorbol-13-acetate (TPA) treatment. Pretreatment of O. echioides extract (5 mg & 10 mg/Kg b.wt) in both the studies with BPO+UVB and TPA restored the levels of reduced glutathione (GSH) and cellular protective enzymes (p < 0.05). Concomitantly, malondialdehyde (MDA) formation and hydrogen peroxide (H2O2) content were also reduced significantly (p < 0.05) at both the doses. The promotion parameters tested (ornithine decarboxylase activity and DNA synthesis) were also significantly suppressed (p < 0.05). Thereafter, we proceeded with studies on mouse skin carcinogenesis. After ten days of 7,12-dimethylbenz(a)anthracene (DMBA) treatment, twice-weekly applications of croton oil for 20 weeks resulted in 100% incidence of tumors in the animals. However, O. echioides showed reduction in the number of tumors/ mouse and percentage of tumor bearing mice at the end of the study. The study was further histologically confirmed. The protective activity of the plant might be due to the two major constituents (alkannins and shikonins) present in the plant. O. echioides is thus, proposed to be helpful in prevention of experimental skin carcinogenesis.
Sharma
Sonia
S
Section of Chemoprevention and Nutrition Toxicology, Department of Medical Elementology and Toxicology, Faculty of Science, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi 110062, India.
Khan
Naghma
N
Sultana
Sarwat
S
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity*; D000818:Animals; D001585:Benzoyl Peroxide / Q000008:administration & dosage; D028082:Boraginaceae / Q000737:chemistry*; D002273:Carcinogens / Q000633:toxicity; D002374:Catalase / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D003436:Croton Oil / Q000633:toxicity*; D004247:DNA / Q000378:metabolism; D005260:Female; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D009955:Ornithine Decarboxylase / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D008517:Phytotherapy; D010936:Plant Extracts / Q000627:therapeutic use*; D012867:Skin / Q000187:drug effects / Q000528:radiation effects; D012878:Skin Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity; D014466:Ultraviolet Rays
D002273:Carcinogens; D010936:Plant Extracts; D008315:Malondialdehyde; D015127:9,10-Dimethyl-1,2-benzanthracene; D003436:Croton Oil; D004247:DNA; D006861:Hydrogen Peroxide; D002374:Catalase; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D009955:Ornithine Decarboxylase; D005978:Glutathione; D013755:Tetradecanoylphorbol Acetate; D001585:Benzoyl Peroxide