Inflammation plays a vital role in the process of carcinogenesis and anti‐inflammatory properties of phytochemicals are gaining more attention in the chemoprevention of cancer. The present study was designed to evaluate the anti‐inflammatory potential of citronellol (CT) on 7,12‐dimethylbenz(a)anthracene (DMBA)‐induced mammary carcinogenesis in rats. The inflammation‐associated gene and protein markers were analyzed by immunohistochemistry, reverse transcription polymerase chain reaction, and Western blot techniques. Markers such as nuclear factor‐kB (NF‐kB), tumor necrosis factor‐α, interleukin‐6 (IL‐6), cyclooxygenase‐2, macrophage inflammatory protein‐1α, and inducible nitric oxide synthase are upregulated in DMBA‐alone–treated mammary tumor tissues. The oral administration of CT (50 mg/kg BW) to DMBA‐treated rats significantly downregulated the expression NF‐kB and other inflammatory markers, and also increased the level of IL‐10 in mammary tissues. The results suggested that the anti‐inflammatory potential of CT prevented the incidence of chemical carcinogen‐induced mammary cancer in rats.
Breast cancer is one of the most common cancers among women world wide and its incidence is on tremendous increase. The present study is aimed to analyze the dose‐dependent chemopreventive efficacy of citronellol on 7,12‐dimethylbenz(a)anthracene (DMBA)‐induced rat mammary carcinogenesis. The mammary tumor was induced through a single dose of DMBA (25 mg/rat) injected subcutaneously near the mammary gland of rats. In DMBA‐injected rats, 100% tumor incidence, increased tumor volume, and tumor burden along with loss of body weight were observed. Biochemical analysis revealed the increased levels of phase I detoxification proteins (cytochrome P450 and b5) and decreased activities of phase II detoxification enzymes (glutathione‐S‐transferase and glutathione reductase) in hepatic and mammary tissues. The levels of enzymatic and non‐enzymatic antioxidants (superoxidedismutase, catalase, glutathione peroxidase, and (GPx) and reduced glutathione) were decreased and lipid peroxidation by‐products (thiobarbituric acid reactive substance and lipid hydroperoxide) got increased in plasma and mammary tissues. Oral administration of different doses of citronellol (25, 50, and 100 mg/kg body weight) to DMBA‐treated rats for 16 weeks absolutely inhibited the tumor incidence and restored the biochemical parameters near to normal level in 50 and 100 mg doses whereas the histopathological studies also supported the biochemical findings. Hence, the result suggests that the citronellol of 50 mg/kg body weight exerted significant chemopreventive effects and can be considered as a minimum optimum dose in the prevention of mammary carcinogenesis.
The present study was aimed to investigate the dose dependent chemopreventive activity of brucine against 7, 12-dimethylbenz (a) anthracene induced mammary gland tumorigenesis in rats. The mammary tumor was induced by a single dose of DMBA (25 mg/rat) injected subcutaneously near the mammary gland. We observed reduced body weight and increased in tumor incidence the total number of tumors and tumor volume in DMBA alone injected rats and also observed decreased antioxidant status (SOD, CAT, GPX, and GSH) and increased lipid peroxidation (TBARS and LOOH) in plasma and mammary tissues. Increased levels of CYP450, Cyt-b5 and decreased levels of phase II (GST and GR) biotransformation enzymes noticed in the liver and mammary tissues. Further increased levels of lipid profile (TC, TG, PL, and FFA) and lipoprotein (LDL and VLDL) were noticed. Whereas, decreased the level of HDL in plasma and decreased levels of PL and FFA in mammary tissues. Oral administration of brucine in different doses (2, 4 and 8 mg/kg bw) inhibited the tumor incidence and restored the levels of biochemical markers near to normal in dose responsive manner. Biochemical findings are supported by histopathological studies. The results suggest that brucine at a dose of 8 mg/kg bw shows more significant chemopreventive activity in DMBA-induced mammary carcinogenesis.
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