One-year chronic toxicity study of Aloe arborescens Miller var. natalensis Berger in Wistar Hannover rats. A pilot study

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Abstract

This study was conducted to evaluate the chronic toxicity of Aloe arborescens Miller var. natalensis Berger (ALOE) in the diet at doses of 4.0%, 0.8% or 0.16% to groups of male and female Wistar Hannover rats. No deaths occurred at any dose level throughout the treatment period. Both sexes receiving 4.0% showed diarrhea, with a reduced body weight gain. Increase of WBCs in the male 4.0% group, decrease of Hb in the female 4.0% and 0.8% groups, decrease of IP in the male 4.0% and 0.8% groups and female 4.0% group, and decrease of Ca and ALT in the female 4.0% group were observed. Relative kidney weight showed increase in the female 4.0% group and relative heart and brain weights were decreased in the female 4.0% and 0.8% groups. Histopathologically, both sexes receiving 4.0% showed severe sinus dilatation of ileocecal lymph nodes, and yellowish pigmentation of ileocecal lymph nodes and renal tubules. In conclusion, the no observed adverse effect level (NOAEL) for ALOE was the 0.16% in diet, which is equivalent to 87.7 and 109.7 mg/kg/day in males and females, respectively.

Introduction

Aloe arborescens Mill var. natalensis Berger (designated as ‘ALOE’), a member of the family Liliaceae, is called Kidachi aloe in Japan and is valued as a family medicine for gastrointestinal complaints, skin injuries and burns. Various pharmacological and therapeutic activities of ALOE have been studied, and there have been many reports of anti-inflammatory effects (Fujita et al., 1976), purgative action (Akao et al., 1996), antidiabetic influence (Beppu et al., 2006), and antitumorigenic effects of extracts (Tsuda et al., 1993, Shimpo et al., 2006).

ALOE contains aloin and aloenin as anthranoid (Koshioka et al., 1982, Kuzuya et al., 2001). In human cases, anthranoid-containing laxatives use including ALOE has been suggested a risk factor of colorectal tumors (Nascimbeni et al., 2002, Willems et al., 2003). However, in F344 rats, antitumorigenic effects of ALOE has been reported in colorectal tumorgenesis (Shimpo et al., 2001, Shimpo et al., 2006) and liver preneoplastic lesions (Tsuda et al., 1993). Therefore, the associations of cancer risk and anthranoid-containing laxatives including ALOE are controversial.

In a previous 90-day subchronic toxicity study of rats administered diets containing 0%, 0.25%, 1.0%, 4.0% ALOE, diarrhea, decreased body weight gain and increase of leucocytes were evident in the 4.0% males and females (Kamiya, 2002). However, no oral toxicity data with longer administration have hitherto been available, despite the fact that ALOE is widely used not only as a food additive but also as a health-food material. Therefore, in this study, we conducted a one-year chronic toxicity study at dietary concentrations up to 4.0% to more fully evaluate the potential toxicity of ALOE.

Section snippets

Chemicals

Whole leaf powder of ALOE was obtained from Nippon Funmatsu Yakuhin (Osaka, Japan). The ALOE powder was added directly to the powdered basal diet MF (Oriental Yeast Co., Ltd.; Tokyo, Japan) at concentrations of 0%, 0.16%, 0.8%, and 4.0%, which was then pelleted. Aloenin and aloin (barbaloin and isobarbaloin), the major effective elements of ALOE, were measured by Nippon Funmatsu Yakuhin, after storage at room temperature for 2 weeks with use of one batche of ALOE (Table 1).

Experimental animals and housing conditions

A total of 42 male

Survival rates, general condition, body weight, food consumption

In the study, no deaths occurred at any dose levels during the treatment period. Several samples were lost, therefore the number of animals evaluated for the various parameters ranges from 6 to 14. Regarding the general condition, males of the 4.0% group suffered from diarrhea from 1 week after the commencement to the end of study, and the 4.0% females showed a tendency for loose stools. At 4.0% the faeces were yellow in color. No other obvious findings were observed for general condition.

Discussion

The present one-year chronic toxicity study of ALOE at dietary concentrations up to 4.0% showed no treatment-associated deaths in male and female Wistar Hannover rats, and toxicological significant changes were observed in loss of body weight gain, diarrhea, increase of WBC, decrease of Hb, Ca and IP, severe sinus dilatation in ileocecal lymph nodes and increased yellow–brown pigmentation in the lymph nodes and renal tubule.

Diarrhea and reduced body weight gain were observed in both sexes

Acknowledgements

This study was supported by a Grant-in-Aid for Research on Food Sanitation from the Ministry of Health, Labor and Welfare of Japan.

References (16)

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