Action of green tea catechin on bone metabolic disorder in chronic cadmium-poisoned rats

doi:10.1016/S0024-3205(03)00433-8

Life Sciences

Volume 73, Issue 12, 8 August 2003, Pages 1479-1489

https://doi.org/10.1016/S0024-3205(03)00433-8 Get rights and content

Abstract

The purpose of this study was to investigate the effects of green tea catechin on bone metabolic disorders and its mechanism in chronic cadmium-poisoned rats. Sprague-Dawley male rats weighing 100 ± 10 g were randomly assigned to one control group and three cadmium-poisoned groups. The cadmium groups included a catechin free diet (Cd-0C) group, a 0.25% catechin diet (Cd-0.25C) group and a 0.5% catechin diet (Cd-0.5C) group according to their respective levels of catechin supplement. After 20 weeks, the deoxypyridinoline and crosslink values measured in urine were significantly increased in the Cd-0C group. Cadmium intoxication seemed to lead to an increase in bone resorption. In the catechin supplemented group (Cd-0.5C group), these urinary bone resorption marks, were decreased. The serum osteocalcin content in the cadmium-poisoned group was significantly increased as compared with the control group. In the catechin supplemented group serum osteocalcin content values were lower than the control group. The cadmium-intoxicated group (Cd-0C group), had lower bone mineral density than the control group (total body, vertebra, pelvis, tibia and femur). The catechin supplement increased bone mineral density to about the same as the control group. Bone mineral content showed a similar trend to total bone mineral density. Therefore, the bone mineral content of the Cd-0C group at the 20th week was significantly lower than the control group. The catechin supplemented group (Cd-0.5C group) was about the same as the control group. The cause of decreasing bone mineral density and bone mineral content by cadmium poisoning was due to the fast bone turnover rate, where bone resorption occurred at a higher rate than bone formation. The green tea catechin aided in normalizing bone metabolic disorders in bone mineral density, bone mineral content and bone calcium content caused by chronic cadmium intoxication.

Introduction

Cadmium (Cd) has been used industrially to manufacture electro-plates, batteries, alloys and fuels [1]. The increased industrial use of Cd causes contamination of the soil, air and water. The use of phosphatic fertilizer, sewage and cadmium containing bactericide has also caused significant cadmium accumulation in the soil [2]. Cadmium can be ingested through contaminated food or inhaled via cigarette smoke of contaminated air. About 20∼30 mg of cadmium can accumulate in the body our life time 40∼60 years [1].

The effects of acute cadmium intoxication are well characterized. Chronic Cd-intoxication such as Itai-itai disease causes kidney malfunction, calcium absorption disorders and osteoporosis [3], [4], [5]. Bone disorders are a major result of chronic cadmium intoxication. Cadmium directly interferes with the function of 1,25-dihydroxycholecalciferol in the intestinal cells and lowers the calcium resorption by inhibiting the synthesis of calcium binding proteins [6], [7]. During cadmium intoxication, calcium excretion is increased by kidney malfunction, which subsequently causes the loss of bone mineral [8]. Cadmium also directly affects the myeloblast and leads to differentiation of the osteoblast [9]. It can replace calcium in hydroxyapatite crystals, which can promote bone resorption and cause osteomalacia or osteoporosis [9], [10]. Numerous studies on bone metabolism disorders due to cadmium intoxication have been reported. Adams et al. [11] reported that bone loss occurs upon chronic exposure to cadmium. Slemenda et al. [12] reported that cadmium decreases bone mineral density and causes bone fractures. Anderson and Danylchuk [13] reported that in dogs exposed to cadmium, bone formation was decreased due to the cadmium intoxication. Also, Chalkiey et al. [14] reported that people who were exposed to cadmium for a long time had a decreased plasma concentration of 1,25-dihydroxycholecalciferol, which could lead to osteoporosis or osteomalcia. To date, studies on cadmium intoxication have been mostly epidemiological. Most experimental studies, focused on cadmium accumulation on Cd-induced histopathological effects in the liver, kidney or testicles following acute cadmium intoxication [15], [16], [17]. However, classification of pathologic mechanisms affecting clinical phenomena such as bone tissue metabolic disorders caused by chronic cadmium intoxication require long-term studies. Very few studies have examined detoxification mechanisms using natural substances.

Several studies in experimental animals that examined the relationship between cadmium detoxification and nutritious substances showed that some dietary factors can alleviate the cadmium intoxication or lower cadmium accumulation in the body [18]. Detoxification methods include increased, dietary fibers and calcium [19], as well as the optimum amounts of dietary copper and iron with increased dietary calcium and protein [20].

Recently, some natural products have been used to reduce heavy metal accumulation and intoxication by promoting excretion from the body. Kim et al. [21] reported that tea has a cadmium detoxification effect. Green tea catechin, among other natural substances, is known for its various pharmacological benefits. There include decreasing cholesterol level in blood serum [22] as well as increasing anti-oxidation [23], anti-cancer [24], anti-high blood pressure traits [25] along with the possibility of inhibiting platelet coagulation [26]. Green tea detoxification of the body results from inhibiting the absorption of heavy metals as well as increasing their excretion [21]. Catechin is an abundant polyphenol found in green tea. Catechin binds with metal ions to form an insoluble complex-ionic salt used to remove heavy metals.

Detoxification experiments using green tea have shown that green tea has the capacity to complex heavy metals in vitro. Kim et al. [21] reported that green tea inhibits absorption and promotes excretion of heavy metal. However, few studies have been conducted with pure catechin extract to test its detoxification effect particularly with respect to Cd-induced bone metabolic disorders. Therefore, this study was carried out to determine the effects of catechin on bone metabolic disorders following Cd-intoxication.

Section snippets

Experimental animals and diets

Male Sprague-Dawley strain rats weighing 90–100 g were purchased from KRITC (Korea Reasearch Institute of Chemical Technology; Yusung, Korea). The animals were individually housed in stainless steel cages in a room with controlled temperature (20–23 °C) and lighting (alternating 12 h periods of light and darkness) They were fed a pelleted, commercial, non-purified diet for 6 days after arrival. They were randomly divided into one control group and three cadmium groups. The cadmium groups

Urinary deoxypyridinoline, creatinine and crosslink values

In order to observe changes in bone metabolism urine deoxypyridinoline (bone resorption index), creatinine and crosslink values were assessed (Table 2). The deoxypyridinoline in the urine of the Cd-0C group (3512 ± 65.8) is significantly higher than the control group, while the 0.5% catechin group (Cd-0.5C group) had about the same deoxypyridinoline value as in the control group. Urinary creatinine was not affected by Cd-exposure. The urinary crosslink values were calculated by the ratio of

Discussion

This study was carried out to investigate the effects of green tea catechin on bone metabolic disorders and their mechanism. Bone metabolic indices such as bone mineral density, bone mineral content and bone calcium content were measured during the cadmium poisoning periods. In our preliminary study, the effects of calcium were studied using control rats and control rats supplemented with catechin. There was no significant differences on calcium metabolism and bone density between these two

Acknowledgements

This work was supported by Korea Research Foundation Grant (KRF-1996-002-D00075).

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