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  • ThesisItemOpen Access
    ANTICARCINOGENIC ACTIVITY OF CINNAMALDEHYDE AND NANO CINNAMALDEHYDE AGAINST MAMMARY CANCER IN RATS
    (SRI VENKATESWARA VETERINARY UNIVERSITY TIRUPATI - 517 502. (A.P.) INDIA, 2018-05) Ravi, Killi; Ravi Kumar, P(MAJOR); Bharavi, K; Rama Devi, V; VINOO, R
    ABSTRACT: Cancer is a growing health problem in both developing and developed countries. Cancer chemoprevention is defined as the use of natural or synthetic agents that reverse, suppress or arrest carcinogenic and/or malignant phenotypic progression towards invasive cancer. The effectiveness of many anticancer drugs is limited due to their inability to reach the target site in sufficient concentrations and efficiently exert the pharmacological effect on affected cells without harming the healthy cells. Therefore, the search for new anticancer agents with better efficacy and fewer side effects is an ongoing phenomenon. Plant phenolic compounds are a group of secondary metabolites with wide pharmacological activities (Al-Rimawi et al., 2016). Plant polyphenols have drawn increasing attention due to their potent antioxidant properties and their marked effects in the prevention of different oxidative associated diseases such as cancer (Dai and Mumper, 2010). trans- Cinnamaldehyde is a phenolic compound found naturally in various species of the genus Cinnamomum and is used in preparing beverages, medicinal products, perfumes and cosmetics. Nanoparticles (NPs) are versatile agents with a variety of biomedical applications including drug delivery. Keeping this in view, the present study was undertaken to evaluate the anticancer potential of cinnamaldehyde (CNMA) and its nano preparation, the nano zinc cinnamaldehyde (CZN) in chemical induced rat breast cancer model. Further, cinnamaldehyde was also studied for its disposition kinetics in rats. For induction of mammary tumors, fifty days old virgin female Sprague-Dawley rats were administered with single oral dose of 20 mg dimethyl benz(a)anthracene (DMBA). Those rats positive for mammary tumors on 90th day were only selected for further studies. The study was carried out in seven experimental groups viz. normal control (C), DMBA control (DMBA-C), cinnamaldehyde prophylactic (CNMA-P), cinnamaldehyde treatment (CNMA-T), nano cinnamaldehyde control (CZN-C), nano cinnamaldehyde treatment (CZN-T) and tamoxifen (TAM). CNMA-P group rats received cinnamaldehyde (50 mg/kg b.wt) orally starting from the 45th day i.e. five days prior to the DMBA administration and continued to received the same until the end of the study on 120th day. CNMA-T, CZN-C and TAM treatment groups received the respective treatments for a period of 30 days beginning from the 90th day. All the animals were sacrificed on 120th day. Plasma concentration of cinnamaldehyde and cinnamic acid were estimated in rats administered with cinnamaldehyde at a dose rate of 500 mg/kg b.wt. From the pharmacokinetic study it was evident that cinnamaldehyde is rapidly converted into cinnamic acid (CA). Apparent volume of distribution (Vd) and plasma clearance (Cl) were high for CNMA but its AUC0-t, MRT and t1/2 values were low when compared to CA. Tumor volume, tumor multiplicity, tumor burden, body weight, tissue antioxidant and peroxidation status and various plasma biochemical parameters including total sialic acid (TSA) levels were assessed in all experimental groups. In addition tumor latency period was recorded in CNMA-P group. Mammary tumor tissues were subjected to light and electron microscopic examination for pathological changes and immunohistological studies for the presence of estrogen and progesterone receptors. Prophylactic treatment with cinnamaldehyde increased the tumor latency period and decreased the tumor volume, tumor burden and tumor multiplicity. Compared to DMBA control group, cinnamaldehyde and its nano preparation showed favourable results in terms of tissue antioxidant profiles and plasma biochemical parameters. Mild to moderate regressive changes were observed in various treatment groups. However tamoxifen treated rats showed greater extent of favourable changes in terms of tumor histology. The study revealed that, cinnamaldehyde (CNMA) and nano zinc cinnamaldehyde (CZN) have mild degree of anticancer effects, with CZN being little more effective than CNMA. However CNMA was more effective when used prophylactically than when used as a therapeutic agent. Hence, it is likely that CNMA can reduce the possibility of breast cancer occurrence and severity when used prophylactically.