Chemomodulatory Influence of Ferula asafoetida on Mammary Epithelial Differentiation, Hepatic Drug Metabolizing Enzymes, Antioxidant Profiles and N-methyl-N-Nitrosourea-Induced Mammary Carcinogenesis in Rats

Authors: Mallikarjuna G.U.^{1, 2, 3}; Dhanalakshmi S.²; Raisuddin S.³; Ramesha Rao A.¹

Source: Breast Cancer Research and Treatment, Volume 81, Number 1, September 2003 , pp. 1-10(10)

Publisher: Springer

Abstract:

The present study was conducted to ascertain the modulatory influences of Ferula asafoetida L. (asafoetida, flavoring agent) on the mammary epithelial tissue differentiation, hepatic drug metabolizing enzymes, antioxidant profiles and N-methyl-N-nitrosourea (MNU)-induced mammary carcinogenesis in Sprague-Dawley rats. Feeding with two doses of asafoetida (1.25 and 2.5% w/w in diet) showed a remarkable increase in the development and differentiation of ducts/ductules (p < 0.01–0.005), lobules (p < 0.005) and a decrease in terminal end buds (p < 0.05–0.005) as compared to both normal and MNU-treated control animals. To assess the biochemical parameters, effect of asafoetida on drug-metabolizing enzymes was evaluated in the liver of rats. Asafoetida treatment significantly reduced (p < 0.05) the levels of cytochrome P450 and b5. There was an enhancement in the activities of glutathione S-transferase (p < 0.05–0.005), DT-diaphorase (p < 0.05–0.01), superoxide dismutase (p < 0.01–0.005) and catalase (p < 0.05–0.005) and in the level of reduced glutathione (p < 0.05–0.005), followed by asafoetida treatment. Also, asafoetida significantly restored the level of antioxidant system, depleted by MNU-treatment. The strengthening of antioxidant system by the lower and higher doses of asafoetida in the presence and absence of MNU was further substantiated by a significant inhibition (p < 0.005) in lipid peroxidation as measured by thiobarbituric acid-reactive substances (TBARS) in the liver of rat. Further, in long-term animal studies, where MNU was used to induce mammary carcinogenesis, asafoetida treatment resulted in a significant reduction in the multiplicity (p < 0.001) and size of palpable mammary tumors (p < 0.005–0.001) and a delay in mean latency period of tumor appearance (p < 0.005). Together, these findings indicate the chemopreventive potential of asafoetida against MNU-induced mammary carcinogenesis. Thus, asafoetida needs further investigation with regard to identification and characterization of its active principle(s) and mechanism of action, for this compound to be developed as a potential chemopreventive agent for human cancers.

Keywords: chemoprevention; Ferula asafoetida; mammary carcinogenesis; mammary gland differentiation; N-methyl-N-nitrosourea; xenobiotic metabolism

Language: English

Document Type: Research article

Affiliations: 1: Cancer Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi, India 2: Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Health Science CTR, Denver, CO, USA 3: Department of Medical Elementology and Toxicology, Jamia Hamdard (Hamdard University), New Delhi, India

Publication date: 2003-09-01

• In this: publication
• By this: publisher
• In this Subject: Obstetrics & Gynecology ,  Oncology
• By this author: Mallikarjuna G.U. ;  Dhanalakshmi S. ;  Raisuddin S. ;  Ramesha Rao A.

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