Collagen peptides have garnered significant attention as functional foods across multiple fields due to their capacity to regulate physiological and hormonal processes, offering numerous advantages. However, despite their broad range of applications, comprehensive research on the potential toxicity of these substances remains lacking. Therefore, this study sought to assess the acute oral toxicity of a collagen peptide derived from skate (Raja kenojei) skin (CPSS) in both rats and dogs. In the rat model, CPSS was orally administered at doses of 300 and 2,000 mg/kg to Sprague-Dawley rats. An escalating single-dose oral toxicity assessment at doses of 500, 1,000, and 2,000 mg/kg was carried out in beagle dogs with 3-day intervals between doses. Throughout the 14-day post-administration assessment period, clinical signs, mortality rates, changes in body weight, and necropsy observations were closely monitored. After oral administration, no signs of toxicity associated with CPSS were observed in either rats or dogs. Therefore, the oral LD50 (approximate lethal dose for 50% mortality) for CPSS in rats was determined to exceed 5,000 mg/kg, and the maximum tolerated dose for dogs was estimated to be above 2,000 mg/kg. Consequently, this study offers safety data on the use of CPSS in functional foods and medicinal applications.

Iron deficiency is known to be a common nutritional disorder in many countries, especially among children, women of childbearing age and pregnant women. SUNACTIVE Fe-P80 is a new type of iron supplement that applies nanotechnlateology for the purpose of overcoming the disadvantages of food supplements. This study was conducted to investigate the potential adverse effects of a 28-day repeated oral dose of SUNACTIVE Fe-P80 in rats. SUNACTIVE Fe-P80 was administered once daily by gavage to Sprague-Dawley rats for 28 days at doses of 0, 500, 1,000, and 2,000 mg/kg/day. Additional recovery groups from the control and highdose groups were observed for a 14-day recovery period. At the scheduled termination, the animals were sacrificed, their organs weighed, and blood samples collected. There were no treatment-related effects in the context of clinical signs, body weight, food intake, ophthalmoscopy, urinalysis, necropsy findings, organ weights, and hematologic, serum biochemical and histopathological parameters at any dose tested. Under the present experimental conditions, the no-observed-adverse-effect level of SUNACTIVE Fe-P80 was ≥ 2,000 mg/kg/day in both the sexes, and no target organs were identified. Thus, the results suggest that SUNACTIVE Fe-P80 is relatively safe, as no treatment-related adverse effects were observed following a 28-day repeated oral dose experiment.

Osteoporosis is a major worldwide public health problem that poses a great economic burden to society. Puerariae Radix, the dried root of Pueraria lobata (Wild.) Ohwi, has been widely used in Asia. This study investigated the effects of Puerariae Radix (PR) on bone loss in ovariectomized (OVX) mice. C3H/HeN mice (10 weeks old) were divided into sham and OVX groups. The OVX mice were treated with vehicle, 17β-estradiol (E2), PR (oral administration, 250 mg/ kg/day) or PR (intraperitoneal administration, 50 mg/ kg/every other day) for 6 weeks. Grip strength, uterus weight, serum alkaline phosphatase (ALP), estradiol concentration and osteoclast surface levels were measured. Tibiae were analyzed using microcomputed tomography. There were no significant differences in the degree of grip strength, body weight and uterine weight between OVX group and PR-treated group. As compared with the OVX group, the serum estradiol levels were significantly increased in the PR-treated group. PR (i.p.) significantly preserved trabecular bone volume, trabecular bone number, structure model index and bone mineral density of proximal tibiae metaphysic. The administration of PR lowered serum ALP and osteoclast surface levels in OVX mice, suggesting that PR can reduce the bone turnover rate in mice. The results indicate that the supply of PR can prevent OVX-induced bone loss in mice.

An evidence suggests that even low-dose irradiation can lead to progressive cognitive decline as well as memory deficits in both humans and experimental animals in part due to hippocampal dysfunction. To determine whether or not green tea (GT) and epigallocatechin gallate (EGCG) could attenuate memory impairment as well as suppress hippocampal neurogenesis, passive avoidance and object recognition memory test as well as TUNEL assay and immunohistochemical detection with markers of neurogenesis (Ki-67 and doublecortin (DCX)) were performed using adult mice treated with relatively low-dose gamma irradiation (2.0 Gy). GT was administered intraperitonially at a dosage of 50 mg/kg of body weight at 36 and 12 hr pre-irradiation and at 30 minutes post-irradiation, or orally at a dosage of 250 mg/kg of body weight/day for 7 days before autopsy. EGCG (25 mg/kg of body weight) was administered intraperitonially at 36 and 12 hr pre-irradiation and at 30 minutes post-irradiation. In the passive avoidance and object recognition memory test, mice trained for 1 day after acute irradiation (2 Gy) showed significant memory deficits compared with sham controls. The number of TUNEL-positive apoptotic nuclei in the dentate gyrus increased by 12 h after irradiation. In addition, the numbers of Ki-67- and DCX-positive cells significantly decreased. GT treatment prior to irradiation attenuated memory defects, blocked apoptotic death, as well as reduced the number of DCX-positive cells. Therefore, GT may attenuate memory defects in adult mice exposed to a relatively low dose of radiation possibly by inhibiting the detrimental effects of irradiation on hippocampal neurogenesis.

Panax ginseng, also known as Korean ginseng, has long been used as a broad tonic in Oriental medicine to augment vitality, health, and longevity, particularly in older people. This study investigated the effects of Korean red ginseng (RG) on bone loss in ovariectomized (OVX) mice. C3H/HeN mice (10-weeks-old) were divided into sham and OVX groups. OVX mice were treated with vehicle, 17β-estradiol (E2), RG (oral administration, 250 mg/kg/day), or RG (intraperitoneal administration, 50 mg/kg/every other day) for 6 weeks. Serum E2 concentration and alkaline phosphatase (ALP) activity were measured. Tibiae were analyzed using microcomputed tomography. Biomechanical properties and osteoclast surface level were measured. There was no significant difference in the degree of grip strength, body weight, uterine weight, mechanical property, tibiae length, or tibiae weight between the OVX and RG-treated groups. Compared with the OVX group, the serum ALP level was significantly lower in the RG-treated groups. Serum E2 levels and osteoclast surface levels did not change between the OVX and RG-treated groups. RG could not preserve trabecular bone volume, trabecular bone number, trabecular separation, trabecular thickness, structure model index, or bone mineral density of the proximal tibiae metaphysic. In conclusion, there was no definite effect of RG on OVX-induced bone loss in C3H/HeN mice.

The present study investigated the urinary tract toxicity of melamine alone or in combination with cyanuric acid in rats. Male rats were orally administered melamine alone (800 mg/kg) or melamine plus cyanuric acid (50 mg/kg each) for 3 consecutive days. Although melamine treatment did not show any significant difference in body weight, kid- ney or urinary bladder weight, serum blood urea nitrogen (BUN) or creatinine levels, it caused a decrease in urinary pH and mild histopathological alterations in the kidney and urinary bladder. In contrast, co-administration of melamine and cyanuric acid induced a decrease in body weight, an increase in kidneys and urinary bladder weights, and an elevation in serum BUN and creatinine levels, which were not observed in animals treated with melamine alone. His- topathological examination showed that the incidence and severity of histopathological lesions in the kidney and uri- nary bladder were much higher than those in the melamine group. Urinalysis revealed an increase in urine occult blood, leukocytes and protein and a decrease in urinary pH. These results indicate that concomitant administration of cyanuric acid synergistically potentiated the urinary tract toxicity induced by melamine in rats. In this study, we first demon- strated the synergistic toxic effects of melamine in combina- tion with cyanuric acid on urinary bladder and urinalysis in rats.

To evaluate the acute to chronic effects of crude oil exposure on hematological and blood biochemical toxicities, Sprague-Dawley rats were given oral doses of 0, 50, or 100 mg/kg BW/day of Iranian heavy crude oil for a period of four weeks. In the acute phase of exposure (one day after four weeks of oil treatment), decreases in weight of thymus, serum level of interferon gamma (IFN-γ), superoxide dismutase (SOD), and catalase activities in liver or kidney, and increase in weight of adrenal gland occurred after oral administration of crude oil. In body weight, histopathological examination, hematological and blood biochemical analyses in the acute phase of exposure, no significant differences were observed among the experimental groups. In the subchronic and chronic phase of exposure (two months and six months after four weeks of oil treatment), the changes of biomarkers were normalized, except the indicators of oxidative stress. Our findings showed that the bioassay on the indicators of oxidative stress is a sensitive method for determining exposure to crude oil in rats.

Probiotics, enzymes, organic acids, oligosaccharides, antioxidants, and other functional materials are actively being explored as alternatives to antibiotics. Probiotics include live beneficial microorganisms that colonize the intestinal tract and competitively inhibit attachment and growth of harmful microbes. Probiotics also increase feed efficiency by assisting in nutrient absorption and digestion. The current study was conducted in order to evaluate the effect of a new probiotic, CS-A, as a dietary supplement of a fermented product on growth performance, feed intake, and feed conversion efficiency in broiler chickens, and to evaluate its value as an alternative for antibiotics used as a feed additive. Antibacterial and anti-inflammatory effects of CS-A were investigated in vitro and the in vivo effects of a constant concentration of supplemented CS-A on growth rate and feed efficiency were evaluated. In addition, the safety of CS-A was assessed by examination of common symptoms and mortality. Determination of minimal inhibitory concentration revealed an excellent antibacterial effect of CS-A. Cytotoxicity was low and anti-inflammatory effects were achieved at the effective concentration of CS-A. Supplementation with 0.1% CS-A resulted in a feed efficiency score of 1.84 in broilers, compared to 2.00 in the control group. There were no adverse clinical findings, necropsy findings, hematology, and altered serum biochemistry parameters, and no mortality. Thus, it is concluded that CS-A is safe and effective as a feed additive.

This study was performed to investigate the anti-obesity and anti-lipidemic ability of linalool (LL) in ApoE deficient mice fed a high-fat diet (HFD). Mice were divided into four experimental groups of eight each. Mice in the control group received a basic diet and oral repeated dose of the vehicle only for 12 weeks; mice in the HFD group received a HFD and oral repeated dose of the vehicle only for 12 weeks; and the HFD&LL25 and HFD&LL50 groups received a HFD and oral repeated dose of LL 25 and 50 mg/kg/day for 12 weeks, respectively. Mice in the HFD group showed a significant increase in body weight, spleen weight, and adipose tissue weight, compared with the control group. An increase in the serum levels of aspartate aminotransferase and alanine aminotransferase activities, total cholesterol (T-CHO), triglyceride (TG), and low density lipoprotein cholesterol was also observed in the HFD group. Histopathological examinations showed severe liver injuries, characterized by extensive fatty changes and hepatocyte degeneration/necrosis. On the contrary, oral administration with LL resulted in significantly improved HFD-induced obesity and hyperlipidemia, indicated by a decrease in adipose tissue weight, T-CHO, TG, and histopathological lesions. The results indicate that LL suppressed HFD-induced obesity, hyperlipidemia, hypercholesterolemia, and hepatic steatosis, suggesting that LL might be a promising adjuvant therapy for treatment of these metabolic disorders related to corpulence.

This study was conducted in order to evaluate the anti-inflammatory activities of Phellinus linteus (PL) water extract against carrageenan- and cotton pellet-induced acute and chronic inflammation in rats. Animals were divided into four experimental groups for conduct of acute and chronic inflammations studies: the vehicle control group, positive control group (aminopyrine 100 mg/kg), PL 10 mg/kg group, and PL 20 mg/kg group. Oral administration of PL water extract has dose-dependent anti-inflammatory effects against both acute and chronic inflammation models. In carrageenan-induced paw edema, significant inhibition was observed at 0.5 and 1 h in the PL 10 mg/kg group and at 0.5, 1, 2, 3, 4, and 6 h in the PL 20 mg/kg group. In cotton pellet-induced granuolma formation, PL water extract at 10 and 20 mg/kg/day also showed significant inhibition in dry weights of granuloma. Results of the free radical scavenging assay showed that PL has a dose-dependent scavenging activity against 2,2-diphenyl-1-picrylhydrazyl free radicals. The results obtained in this study indicate that this plant material may be used beneficially as an anti-inflammatory agent having antioxidant action.