Effect of Fucoxanthin Administration on Thyroid Gland Injury Induced by Cadmium in Mice.

Abstract

The intervention effect of fucoxanthin, which is reportedly a powerful antioxidant, on cadmium-induced thyroid damage in mice was evaluated. Animals (N = 120) were divided into control group (given pure water, N = 20) and CdCl2-exposed group (given CdCl2 orally at a dose of 30 mg/kg body weight (bw)/day for 30 days, N = 100). Besides, the CdCl2-exposed group was divided into the following 5 groups (N = 20) to evaluate the intervention effect of fucoxanthin: (1) negative control group (NCG; animals were supplied with pure water); (2) positive control group (PCG; animals were supplied with 50 mg/kg bw/day thyroid tablets. Thyroid tablets are made from the thyroid glands of pigs, cattle, sheep and other food animals (the main components of T4). But because they are extracts of the thyroid glands, they may contain a small amount of T3. The specific amount of T3 is unknown.); (3) low fucoxanthin concentration group (F1; animals were supplied with 10 mg/kg bw/day fucoxanthin); (4) medium fucoxanthin concentration group (F2; animals were supplied with 25 mg/kg bw/day fucoxanthin); (5) high fucoxanthin concentration groups (F3; animals were supplied with 50 mg/kg bw/day fucoxanthin). A 14-day treatment was conducted for these animals. The levels of T4, T3, MDA, ascorbate peroxidase (APX) and catalase were measured, and the expression levels of Bax, Bcl-2, ERK1, ERK2, MEK1, eIf2α, p-eIf2α, GRP78 and GRP94 genes were determined using real-time reverse transcriptase-polymerase chain reactions (RT-PCR). In addition, tissue histopathology and ultrastructure were recorded and analysed. We found that the injection of cadmium chloride (CdCl2) decreased serum T4 and T3 levels to 27.10 ng/ml and 837.74 pg/ml, respectively. In addition, CdCl2 intoxication induced oxidative stress, structural abnormalities and apoptosis in thyroid follicles. Our results showed that the treatment of CaCl-exposed mice with 25-50 mg/kg bw/day fucoxanthin appreciably decreased oxidative stress and apoptosis induced by CdCl2 and restored the microstructural and ultrastructural organisations of the thyroid gland towards normalcy. Compared with the negative control group, fucoxanthin treatment groups showed significant increase in T4 and T3 levels (52.17 ng/ml and 1669.18 ng/ml, respectively; P < 0.05), relieved oxidative stress by decreasing malondialdehyde level and increasing catalase and APX levels and increased apoptosis inhibition through inhibiting the ERK1/2 pathway and preventing endoplasmic reticulum stress in thyroid follicular epithelial cells. Herein, our study provides evidence of the protective effects of fucoxanthin supplementation against thyroid damage and suggests therapeutic potential of this pigment in cases of Cd intoxication and hypothyroidism.