Cancer Letters

Cancer Letters

Volume 183, Issue 1, 8 September 2002, Pages 9-15
Cancer Letters

Inhibitory effects of lemon grass (Cymbopogon citratus, Stapf) extract on the early phase of hepatocarcinogenesis after initiation with diethylnitrosamine in male Fischer 344 rats

https://doi.org/10.1016/S0304-3835(02)00111-8Get rights and content

Abstract

Effects of lemon grass extract (LGE) on hepatocarcinogenesis were examined in male Fischer 344 rats, administered diethylnitrosamine (DEN) at three weekly intraperitoneal doses of 100 mg/kg body weight and partially hepatectomized at the end of week 5. LGE was given at dietary concentrations of 0, 0.2, 0.6 or 1.8% from the end of week 4 for 10 weeks. All rats were sacrificed at the end of week 14. LGE reduced the number of putatively preneoplastic, glutathione S-transferase placental form-positive lesions and the level of oxidative hepatocyte nuclear DNA injury, as assessed in terms of 8-hydroxydeoxyguanosine production. In contrast, LGE did not affect the size of the preneoplastic lesions, hepatocyte proliferative activity, activities of phase II enzymes or hepatocyte extra-nuclear oxidative injury. These results suggest inhibitory effects of LGE on the early phase hepatocarcinogenesis in rats after initiation with DEN.

Introduction

Chemoprevention has attracted attention as one of the most promising strategies to control cancers [1], [2], [3]. Great efforts are thus being made in the search for natural or synthesized agents capable of inhibiting carcinogenic processes [1], [2], [3], [4]. Candidate agents need to be investigated in various animal models to explore the extent of inhibition, underlying mechanisms and possible adverse reactions, in coordination with epidemiological studies to evaluate responses in man [1], [2], [3], [4]. Evidence has now accumulated of anti-mutagenic and/or anti-carcinogenic potential of a variety of food factors, including vitamin C, vitamin E, retinoids, carotinoids and flavonoids [3], [4]. As these are natural compounds present in the human environment, they may serve as particularly good candidates as cancer chemopreventive agents [3], [4], [5]. It should be noted, however, that food factors can exert adverse effects in particular situations [3], [6]. Careful evaluation is therefore required.

Lemon grass (Cymbopogon citratus, Stapf) is a widely used herb in tropical countries, especially in Southeast Asia, and also known as a source of ethno-medicines. Lemon grass extract (LGE), produced with ethanol, exhibits anti-mutagenic activity in various models [7], [8], [9] and retards the growth of fibrosarcoma cells transplanted in mice in association with prevention of lung metastasis [10]. It is thus conceivable that lemon grass contains some components that may be cancer chemopreventive. In fact, LGE has been shown to inhibit rat colon carcinogenesis initiated with azoxymethane [11]. The available data are, however, still limited, and more studies are required to evaluate the cancer chemopreventive properties of lemon grass or its components. The present study was conducted in order to generate information about effects of LGE on carcinogenesis. The liver was selected as a target organ, because hepatocellular carcinomas develop at high incidences in Asian countries, including Thailand and Japan [12], [13].

Section snippets

Animals and chemicals

A total of 30 male Fisher 344 rats, 5 weeks old, were purchased from Japan SLC, Inc. (Hamamatsu, Shizuoka, Japan) and housed at five to a plastic cage with white flake bedding (Kansai Animal Corp., City of Kyoto, Kyoto, Japan) in an air-conditioned room, with a constant temperature of 25±3 °C, a relative humidity of 55±8% and a 12-h dark–light cycle. The rats were acclimatized on a basal diet (CE-2 diet: Clea Japan, Meguro, Tokyo, Japan) for 5 days before the experimentation. They were allowed

Results

During the experimental period, one, one, two and one rats died in groups 1, 2, 3 and 5, respectively, for unknown reasons. Final body weights did not differ among the groups, while relative liver weights in groups 4 and 6 were significantly lower than those in groups 1 and 5, respectively (Table 1). Water intake and food consumption were similar in all groups, and there were no particular macroscopic or microscopic alterations of note (data not shown).

GST-P-positive lesions were significantly

Discussion

The present results indicate that LGE can exert preventive effects on development of DEN-initiated hepatocellular lesions in rats, because LGE significantly decreased the numbers of putatively preneoplastic, GST-P-positive lesions. LGE did not, however, alter the sizes of such lesions, suggesting that LGE may not affect the growth of preneoplastic hepatocyte populations. In fact, neither preneoplastic nor non-neoplastic hepatocytes demonstrated any alteration in the level of proliferation with

Acknowledgements

The authors would like to express their sincere gratitude to Ms Sachiko Nakai, Akiko Nambu, Mariko Okuda, Janya Tipsri and Megumi Yamaguchi (alphabetical order of surnames) for technical support. The first author would especially like to thank Nara Medical University for providing financial support under the Young Scientist Exchange Program. This work was supported in part by a Research Grant from the Princess Takamatsu Cancer Research Fund, Japan, and Scientific Research Expenses for Health

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