title: Interactions of betulinic acid with xenobiotic metabolizing and antioxidative enzymes in DMBA-treated Sprague Dawley female rats.
abstract: Cancer chemoprevention is related to classical epidemiology and involves the use of agents that inhibit, delay, or reverse the carcinogenesis that occurs as a result of accumulation of mutations and increased proliferation. Betulinic acid is known for its cytotoxic effects against a panel of cancer cell lines. In the present study, interactions of betulinic acid (BA) with xenobiotic metabolizing enzymes including mixed function oxidases (cytochrome b5, P420, P450, NADPH cytochrome P450 reductase, and NADH cytochrome b5 reductase), phase II enzymes (GST, DT-diaphorase, γ-glutamyl transpeptidase), LDH, antioxidative enzymes (glutathione reductase, SOD, catalase, ascorbate peroxidase, and guaiacol peroxidase), and lipid peroxidation are studied alone as well as in the presence of 7,12 dimethylbenzanthracene (DMBA)--a potent carcinogen using Sprague Dawley female rats. The effect of BA on reduced glutathione content and protein content is also taken into consideration. It has been found that administration of BA decreased the level of mixed function oxidases that are involved in the conversion of carcinogen to electrophile, elevated the level of phase II enzymes which participated in the removal of electrophiles by sulfation, conjugation etc. It has been found that BA effectively removed or neutralized the reactive species by the action of phase II enzymes and such an effect was reflected from the specific activities of antioxidative enzymes which were found to be lower as compared to positive control (DMBA-treated group) and in some cases even that of untreated control. BA was also found to have a pronounced effect in protecting the animals from lipid peroxidation as evident from the reduced levels of TBARS, conjugated diene, and lipid hydroperoxide formation. This study highlights the role of BA in modulating the activities of xenobiotic and antioxidative enzymes that have putative roles in cancer initiation and proliferation.
authors.affiliation: Department of Botanical and Environmental Sciences, Guru Nanak Dev University, Amritsar 143005, Punjab, India. Electronic address: rajbir_riar@yahoo.co.in.
authors.forename: Rajbir
authors.initials: R
authors.lastname: Kaur
authors.affiliation: Department of Botanical and Environmental Sciences, Guru Nanak Dev University, Amritsar 143005, Punjab, India. Electronic address: sarojarora.gndu@gmail.com.
authors.forename: Saroj
authors.initials: S
authors.lastname: Arora
mesh_terms: D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000378:metabolism* / Q000494:pharmacology*; D002273:Carcinogens / Q000633:toxicity; D005260:Female; D015227:Lipid Peroxidation / Q000187:drug effects*; D053978:Pentacyclic Triterpenes; D051381:Rats; D017207:Rats, Sprague-Dawley; D014315:Triterpenes / Q000494:pharmacology*; D015262:Xenobiotics / Q000378:metabolism*; D000094062:Betulinic Acid
chemical_list: D016588:Anticarcinogenic Agents; D000975:Antioxidants; D002273:Carcinogens; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; D015262:Xenobiotics; D015127:9,10-Dimethyl-1,2-benzanthracene; D000094062:Betulinic Acid
keywords: 2,6-dichlorophenol-indophenol; 7,12-dimethyl benzanthracene; APOX; Antioxidative enzymes; BA; BSA; Betulinic acid; DCPIP; DMBA; GGT; GST; LDH; Lipid peroxidation; MDA; NAD(P)H:quinone oxidoreductase also known as DT-diaphorase; NQO1; Phase I enzymes; Phase II enzymes; SOD; TBARS; ascorbate peroxidase; betulinic acid; bovine serum albumin; glutathione-S-transferase; lactate dehydrogenase; malondialdehyde; superoxide dismutase; thiobarbituric acid reactive species; γ-glutamyl transpeptidase