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

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.

Elevated Serum Levels of Estradiol Induce Endometrial Hyperplasia Rather than Carcinoma in a Mouse Model Using a Carcinogen

“…MNU is a potent chemical carcinogen [25,26] and is widely used to induce mutations and carcinomas [27]. In this mouse endometrial carcinoma model, carcinoma developed within a relatively short time period (20- 30 weeks); thus, this model is convenient for the analysis of endometrial carcinogenesis.…”

“…This may be due to differences in the route and dose, and duration of E2 administration, or the effects of progesterone in mice with ovaries. MNU reportedly evokes not only various types of DNA damage [25][26][27], but also MSI and subsequent point mutations [30][31][32]. A previous study reported that an intraperitoneal injection of MNU into CD mice resulted in the development of thymic lymphoma and systemic MSI [30], suggesting that MNU impairs MMR function.…”

Antioxidant Potential of Various Extracts fromFerula szovitsiana. in Relation to Their Phenolic Content

“…The oleo-gum resins obtained from this genus are of importance, and have been in use in folk medicine for centuries for curing many human ailments. Also, it was shown that Ferula asafoetida has potent antioxidant activity and can afford protection against free radical-mediated diseases such as carcinogenesis (Malli-Karjuna et al, 2003). A literature survey showed that no study has been done on antioxidative stress activity of F. szovitsiana DC.…”

INDIAN TRADITIONAL MEDICINE - A CONGLOMERATION OF ANCIENT KNOWLEDGE AND MODERN SCIENCE (21-22 July 2016: Phytocongress | Sastra University)

“…Many researchers proved its efficacy in gastric ailments [71] such as ulceration, gastric irritation, and acid peptic diseases. It is also being used as an antispasmodic and digestive [72]. Apart from that, it is a potent anti-oxidant and Anticancer agent especially for the breast cancer and also possess antifungal activity (Fatehi et al).…”