Safety assessment of European cranberrybush (Viburnum opulus L.) fruit juice: Acute and subacute oral toxicity.

European cranberrybush (ECB) (Viburnum opulus L.) fruits are abundant in phenolic compounds associated with various health benefits. However, the toxicity and safety of ECB juice have not been systematically studied. In the present study, acute and subacute oral toxicities of ECB fruit juice were evaluated on Sprague-Dawley rats and BALB/c mice to establish a toxicity profile. In acute tests, a single administration of 2000 mg/kg body weight of extract to rats exhibited no clinical signs of toxicity or mortality, indicating that the lethal dose (LD50) was over 2000 mg/kg. In subacute tests, repeated administration for 28 days at 0 (control), 500, and 2000 mg/kg doses of extract in mice did not display adverse clinical signs or deaths. However, in the 2000 mg/kg subacute group, platelet counts were significantly high, which correlated with histopathological analyses revealing that ECB extract at 2000 mg/kg was toxic to the kidney, liver, and adipose tissue. The NOAEL value of ECB extract was found as 500 mg/kg/day, but further sub-chronic and chronic toxicity studies are warranted to comprehensively evaluate the long-term safety implications. The study's results emphasize the importance of considering the dosage of dietary supplements containing high levels of phenolic compounds over an extended period to avoid potential cumulative effects from prolonged consumption of high doses.

Effects of soy-containing infant formulas on thyroid gland in rats.

BACKGROUND: Effects of soy-containing infant formulas on the thyroid gland is not clear. We aimed to evaluate the effects of infant formulas with different quantities of soy content on the functional and histopathological characteristics of the thyroid gland. METHODS: Twenty-eight female Sprague-Dawley rats were divided into four groups. Group 1 was fed with standard pellet rat food (8 g/day); group 2 soy-free infant formula (8 g/day); group 3 low-dose (1.12 g/100 mL) soy-containing formula (8 g/day), and group 4 high-dose (2.64 g/100 mL) soy-containing formula (8 g/day). Blood samples were collected from the subjects on day 0, 30, 60, and 90 to evaluate thyroid functions. All subjects were sacrificed on day 90. Thyroid glands were excised and examined histopathologically. RESULTS: Serum levels of free T3, free T4, TSH, anti-TPO, and anti-TG were significantly higher in Group 4 compared to other groups (P<0.001, P<0.01, P<0.001, P=0.002). No differences were found in the histopathological findings between the groups. CONCLUSIONS: Infant formulas with high soy content induce hyperthyroidism with high TSH levels. High levels of anti-TPO and anti-TG suggest that observed changes might have occurred via inflammatory mechanism.

Sodium Pentaborate Pentahydrate ameliorates lipid accumulation and pathological damage caused by high fat diet induced obesity in BALB/c mice.

BACKGROUND: Obesity is one of the most popular topic in the field of research. In order to defeat this highly widespread disease, the mechanism of fat accumulation at the molecular level and its elimination are crucial. The use of boron has been showing promising results during the recent years. METHODS: In this study, anti-obesity potential of Sodium Pentaborate Pentahydrate (SPP) used as a dietary supplement on BALB/c mice fed with a high-fat diet was evaluated. Mice were divided into four groups with different diets, consisting of a normal diet, a high-fat diet (HFD) (containing 60 % fat), a HFD-supplemented with 0.5 mg/g body weight (BW) of SPP and a HFD-supplemented with 1.5 mg/g body weight (BW) of SPP. The animals were then observed for 10 weeks and physically monitored, and were sacrificed at the end of the experiment for physical and physicochemical evaluation. RESULTS: According to the physical parameters measured -body weight, food and water intake ratios-, the results indicate that SPP decreased weight gain in a dose dependent manner. Measurement of the hormone levels in the blood and fat accumulation in organs of mice also supported the anti-obesity effects of SPP. Expressions of adipogenesis related genes were also negatively regulated by SPP administration in white adipose tissue (WAT) tissue. CONCLUSION: These findings promise a treatment approach and drug development that can be used against obesity when SPP is used in the right doses. As a future aspect, clinical studies with SPP will reveal the effect of boron derivatives on obesity.

Potential Effect of 1,25 Dihydroxyvitamin D3 on Thioacetamide-Induced Hepatotoxicity in Rats.

BACKGROUND: 1,25 Dihydroxyvitamin D3 (1,25(OH)2D3) modulates inflammation and immune responses. Deficiency of 1,25(OH)2D3 was found to be associated with the risk of cancer, cardiovascular disease, osteoarthritis, infections, and autoimmune diseases. This study evaluated the effect of 1,25 dihydroxyvitamin D3 1,25(OH)2D3 on thioacetamide (TAA)-induced acute liver injury in rats. MATERIALS AND METHODS: Rats were treated with either saline or 1,25(OH)2D3 (0.30 µg/kg; orogastrically) for 15 d. Starting from day 13, TAA (200 mg/kg; intraperitoneally) was given for 3 d. On day 15, all rats were euthanized. Liver and blood samples were collected. RESULTS: TAA caused severe damage, increased lipid peroxidation with reductions in endogenous antioxidants, increased apoptosis, increased production of reactive oxygen species, and elevated inducible nitric oxide synthase (iNOS), and nuclear factor kappa B (NF-κB) expression in liver. Extent of damage was decreased by 1,25(OH)2D3 (P < 0.01). 1,25(OH)2D3 attenuated the increase in malondialdehyde (P < 0.01), increase in myeloperoxidase (P < 0.01), increase in chemiluminescence levels (P < 0.05) and apoptotic activity (P < 0.001). Elevated liver iNOS and NF-κB expression in TAA group was also reduced by 1,25(OH)2D3 (P < 0.001, for iNOS; P < 0.001, for NF-κB). TAA group revealed high serum aspartate transaminase and alanine transaminase (ALT) activities (P < 0.01, for aspartate transaminase; P = 0.08, for ALT) and reduced albumin levels (P < 0.01) compared with control. 1,25(OH)2D3 had no statistically significant effect on these parameters. CONCLUSIONS: 1,25(OH)2D3 provides protection against hepatic injury in a rat model of TAA-induced hepatotoxicity via suppression of inflammatory reaction, oxidative stress, and apoptosis.

An immunohistochemical analysis of the neuroprotective effects of memantine, hyperbaric oxygen therapy, and brimonidine after acute ischemia reperfusion injury.

PURPOSE: This study applies treatment methods to rat retinas subjected to acute ischemia reperfusion injury and compares the efficacy of memantine, hyperbaric oxygen (HBO) therapy, and brimonidine by histopathological examination. METHODS: Thirty adult Wistar albino rats were divided into five groups after retinal ischemia was induced by elevating the intraocular pressure to 120 mmHg. The groups were as follows: group 1: control; group 2: acute retinal ischemia (ARI) model but without treatment group; group 3: memantine (MEM) treatment group; group 4: HBO therapy group; and group 5: brimonidine treatment (BRI) group. In the control group, right eyes were cannulated with a 30-gauge needle and removed without causing any intraocular pressure change. The ARI group was an acute retinal ischemia model, but without treatment. In the MEM group, animals were given a unique dose of intravenous 25 mg/kg memantine by the tail vein route after inducing ARI. In the HBO group, at 2 h following ARI, HBO treatment was applied for nine days. In the BRI group, a 0.15% brimonidine tartrate eye drop treatment was applied twice a day (BID) for seven days before ARI. Twenty-one days after establishing ischemia reperfusion, the right eyes were enucleated after the cardiac gluteraldehyde perfusion method, and then submitted to histological evaluation. RESULTS: On average, the total retinal ganglion cell number was 239.93 ± 8.60 in the control group, 125.14 ± 7.18 in the ARI group, 215.89 ± 8.36 in the MEM group, 208.69 ± 2.05 in the HBO group, and 172.27 ± 8.16 in the BRI group. Mean apoptotic indexes in the groups were 1.1 ± 0.35%, 57.71 ± 0.58%, 23.57 ± 1.73%, 15.63 ± 0.58%, and 29.37 ± 2.55%, respectively. CONCLUSIONS: The present study shows that memantine, HBO, and brimonidine therapies were effective in reducing the damage induced by acute ischemia reperfusion in the rat retina. Our study suggests that these treatments had beneficial effects due to neuroprotection, and therefore may be applied in clinical practice.