A chronic oral toxicity study of marine collagen peptides preparation from chum salmon (Oncorhynchus keta) skin using Sprague-Dawley rat.

Due to the increased consumption of marine collagen peptides preparation (MCP) as ingredients in functional foods and pharmaceuticals, it was necessary to carry out safety requirements in the form of an oral chronic toxicity assessment. In order to define the oral chronic toxicity of MCP, a 24-month feeding study of MCP was carried out. Sprague-Dawley (S-D) rats at the age of four-week of both sexes were treated with MCP at the diet concentrations of 0%, 2.25%, 4.5%, 9% and 18% (wt/wt). The actual food intake and bodyweight of the individual animals were recorded periodically until sacrifice. Blood and urine samples were collected for serum chemistry evaluations and urinalysis. Throughout the experimental period, there was no toxicologically significant difference between the vehicle and MCP-treated animals with respect to the survival rate, body weight, food consumption, urinalysis, clinical biochemistry parameter and relative organ weight in either sex. Moreover, incidences of non-neoplastic lesions in MCP-treated groups did not significantly increase compared with the control group. Under the present experimental conditions, no higher risk of chronic toxic effects was observed in MCP-treated rats at the diet concentrations of 2.25%, 4.5%, 9% and 18% (wt/wt) than in the rats fed with basal rodent diet.

Marine collagen peptides prepared from chum salmon (Oncorhynchus keta) skin extend the life span and inhibit spontaneous tumor incidence in Sprague-Dawley Rats.

To observe the effects of marine collagen peptides (MCPs) prepared from chum salmon (Oncorhynchus keta) skin on life span and spontaneous tumor incidence, Sprague-Dawley rats were fed diets supplemented with MCP at concentrations of 0%, 2.25%, 4.5%, and 9% (wt/wt) from the age of 4 weeks until natural death. There were 40 rats in each group (male:female ratio = 1:1). The results showed that the MCP did not significantly influence body weight or food consumption of rats of either sex throughout the life span; it did dose-dependently inhibit the age-related decrease in the activities of antioxidant enzymes and the age-related increase in the levels of lipid peroxidation product in both sexes. MCP notably increased the mean life span, the life span of the last 30% of the survivors, and the maximal life span; it decreased overall spontaneous tumor incidence of both sexes with significance in the 4.5% and 9% MCP-treated male groups and 9% MCP-treated female group. Compared to the control group, the incidence of death from tumors was decreased in MCP groups in comparison with the control group of both sexes. Therefore, we concluded that MCPs dose-dependently increase life span and decrease spontaneous tumor incidence in Sprague-Dawley rats. Moreover, the antioxidative property of MCPs may be responsible for the increased life span and protection against tumor development.

[The study on the immunomodulating effect of marine protein peptides in mice].

OBJECTIVE: To observe the effects of marine protein peptide (MPP) on immunomodulating in mice and its possible mechanism. METHODS: Female ICR mice (6-8 weeks old) were administered the MPP for 4 weeks with the dose of 0.22 g/kgBW, 0.45 g/kgBW and 1.35 g/kgBW. Spleen and thymus were weighted and cell-mediated immune functions, humoral immune functions, phagocytic functions of mononuclear phagocyte, NK cell activity assays, the T cell subpopulation of the spleen tissue by the flow cytometer and the concentrations of cytokines in serum by cytometric bead array were examined. RESULTS: The capacity of lymphocyte proliferation induced by Con A (0.33 +/- 0.21), DTH response (0.36 +/- 0.11) mm in MPP 0.22 g/kgBW group were significantly increased in comparison with these values in control group (0.15 +/- 0.10) and (0.21 +/- 0.10)mm, respectively, P < 0.05. IgM-PFC number of MPP 0.22 g/kgBW group (1.64 +/- 0.06), 0.45 g/kgBW group (1.59 +/- 0.05) and 1.35 g/kgBW group (1.56 +/- 0.10) were higher than those in control group (1.38 +/- 0.10), P < 0.01; and the level of serum HC50 of MPP 0.22 g/kgBW group (141.00 +/- 23.00) and 0.45 g/kgBW group (130.40 +/- 33.20) were greater than the control (100.30 +/- 19.40) , P < 0.01. The activity of NK cells in MPP 0.22 g/kgBW group (1.672 +/- 0.142) was significantly elevated in comparison with this value in control group (1.392 +/- 0.182), P < 0.05. The percentage of CD4 T helper (Th) cell in spleen of MPP 0.22 g/kgBW group (32.84 +/- 3.776)% and 0.45 g/kgBW group (32.42 +/- 3.507) % was higher than those in control group (25.06 +/- 0.354) %, P < 0.05. The concentrations of IL-2 in serum of MPP 0.22 g/kgBW group 181.06 pg/ml, 0.45 g/kgBW group 94.84 pg/ml and 1.35 g/kgBW group 102.61 pg/ml were higher than those in control group 0.50 pg/ml, P < 0.05; and the level of IL-5 of MPP 0.22 g/kgBW group (38.31) pg/ml was greater than the control 0.50 pg/ml, P < 0.05. Nevertheless, no obvious effects on weight increasing, the ratio of immune organ and body weight and phagocytosis capacity were observed in our study. CONCLUSION: MPP could improve the immune functions in mice, and might be by the mechanism of enhancing the function of Th cells stimulating the secretion of Th1 and Th2 type cell cytokines.

[The lipid-lowering and antioxidative effects of marine collagen peptides].

OBJECTIVE: To determine the relative molecular mass of marine collagen peptides (MCPs) and investigate the effects of MCPs on serum lipids, anti-oxidative enzymes and malondialdehyde (MDA) in hyperlipidemic rats. METHODS: Sephadex G-25, high performance liquid chromatography (HPLC) and matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS) methods were used to determine the relative molecular mass of MCPs. Then 50 healthy male SD rats were divided into 5 groups, which were normal control (NC) group, hyperlipidemic model control (HC) group and 1.0, 3.0, 9.0 g/kgbw MCPs groups, MCPs were orally administered by gavage to rats in MCPs group for 45 consecutive days (2 ml/100 kgbw per day), and the control rats were given vehicle only, all animals (except NC rats) were fed with a high fat diet composed of 79% basic diet, 10% lard, 10% yolk powder and 1% cholesterol. The levels of serum lipids, the content of MDA and activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) in serum were measured. RESULTS: The levels of serum total cholesterol (TC) in 1.0, 3.0, 9.0 g/kgbw MCPs groups were 1.89 +/- 0.29, 2.07 +/- 0.39 and 1.99 +/- 0.29 mmol/L respectively, each of which was significantly lower than that in HC group (3.37 +/- 0.24 mmol/L); low-density lipoprotein cholesterol (LDL-C) levels in 1.0, 3.0, 9.0 g/kgbw MCPs groups were 0.83 +/- 0.16, 1.01 +/- 0.35 and 0.91 +/- 0.26 mmol/L respectively, each of which was significantly lower than that in HC group(2.20 +/- 0.34 mmol/L); triglyceride (TG) levels in 3.0 and 9.0 g/kgbw MCPs groups (0.90 +/- 0.15 and 0.86 +/- 0.12 mmol/L) were reduced significantly compared with that in HC group (1.18 +/- 0.18 mmol/L); MDA level in 9.0 g/kgbw MCPs group was 7.1 +/- 4.1 nmol/ml, which was significantly lower than that in HC group ( 15.9 +/- 9.9 nmol/ml); and atherogenic index (AI) in hyperlipidemic rats fed with 1.0, 3.0, 9.0 g/kgbw MCPs were 1.14 +/- 0.22, 1.16 +/- 0.27 and 0.99 +/- 0.31 respectively, each of which was significantly lower than that in HC group (2.27 +/- 0.55). The activities of SOD in 1.0, 3.0, 9.0 g/kgbw MCPs groups (218.6 +/- 33.2, 242.7 +/- 21.4 and 242.1 +/- 44.8 U/ml) were obviously increased compared with that in HC group (119.7 +/- 47.8 U/ml), and anti-atherogenic index (AAI) were also increased significantly (0.47 +/- 0.04, 0.47 +/- 0.06, 0.51 +/- 0.09 vs 0.31 +/- 0.05). CONCLUSION: MCPs should have antioxidative and lipid-lowering effects, and might play a preventive role in hyperlipidemia and atherogenesis.

[Effects of marine collagen peptide on delaying the skin aging].

OBJECTIVE: To investigate the protective effect of marine collagen peptides (MCPs) on the skin of aged mice induced by D-galactose. METHODS: Subchronic toxicity study was conducted while D-galactose induced subacute aging model was established. D-galactose dose of 0.125 g/kg body weight was intraperitoneally injected daily for 90 days. Marine collagen peptide 0.225, 0.450, 1.350 g/kg body weight were administered by oral gavage. Superoxide dismutase (SOD), catalase (CAT) activity and malondialdehyde (MDA) content in blood serum were measured, along with cutaneous histopathology examination. RESULTS: Epidermal thickness was significantly higher in MCPs treated group. Number and activity of fibroblast in MCPs treated dermis was increased prominently. The activity of SOD in 0.225, 0.450, 1.350 g/kgbw MCPs treated groups were 455.52 +/- 11.39, 460.15 +/- 18.09, 468.59 +/- 27.25 U/ml respectively, each of which was significantly higher than that in model control group; the activity of serum CAT in 0.225, 1.350 g/kgbw MCPs treated groups (21.33 +/- 4.82, 21.69 +/- 1.68 U/ml) were obviously increased compared with that in model control group (17.14 +/- 2.81 U/ml); MDA level in 0.450, 1.350 g/kgbw MCPs treated groups were 5.67 +/- 0.93, 5.76 +/- 1.02 nmol/ml respectively, each of which was significantly lower than that in model control group (7.63 +/- 1.37 nmol/ml). CONCLUSIONS: The results showed that MCPs might play a protective role on skin aging by improving the activity of antioxidant.