• Toxicological Research
• /
• 제25권1호
• /
• pp.29-33
• /
• 2009

Phellinus gilvus (PG) is a widely used mushroom for health promotion. We studied the hepatoprotective effect of the polysaccharide aqueous extract of PG (PGP) against carbon tetrachloride ($CCl_4$)-induced liver injury in rats. Sprague Dawley rats were divided into 5 groups: Normal control, $CCl_4$ control, PGP 50, 100, and 200 mg/kg + $CCl_4$. The levels of serum biochemical parameters, liver lipid peroxide and antioxidant enzymes, and histological appearances were evaluated. The $CCl_4$-induced increments of alanine aminotransferase, asparate aminotransferase, and alkaline phosphatase levels in serum were significantly decreased by PGP-pretreatments. The PGP dose-dependently decreased hepatic malondialdehyde formations in $CCl_4$-treatment groups. Hepatic antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) were elevated by PGP in $CCl_4$-treatment groups. Histopathological evaluation of liver showed that the loss of hepatocytes, fatty changes, swelling and extensive necrosis of hepatocytes in centrilobular regions of the $CCl_4$-treated rats were ameliorated by PGP pretreatment. The PGP has hepatoprotective and antioxidative effects in $CCl_4$-induced liver injury of rat.

• 한국식품위생안전성학회지
• /
• 제29권4호
• /
• pp.383-390
• /
• 2014

The safety of a new natural plant composition (ADP) was assessed on the genotoxicity study and 14-day repeat dose toxicity study. ADP contains a mixed water extract obtained from the mixture of Phellodendron cortex (Phellodendron amurense) and Anemarrhena rhizoma (Anemarrhena asphodeloides), and poses the contractile properties mediated by alpha-adrenoceptor of the prostate and urethra as well as antioxidant and anti-inflammatory properties. In order to evaluate genetic safety, in vivo micronucleus test was performed in ICR mice orally administered with three dose levels of 1250, 2500, 5000 mg/kg body weight, and vehicle and positive control. In the 14 days study, Sprague-Dawley rats were treated with ADP at the dose levels of 500, 1000, 2000 mg/kg once a day, and clinical signs, body weights, hematology, serum biochemistry, necropsy findings and organ weights were monitored and examined. In experimental results, ADP treatment, compared with vehicle control, did not induce the micronucleated erythrocytes from mouse bone marrow. In the 14 days study, any significant and toxicological differences in all measurements of parameters were not observed in ADP treatment groups of animals, compared with vehicle treatment. The No-Observed-Adverse-Effect-Level (NOAEL) of ADP in the 14 days study was determined to be greater than 2000 mg/kg/day in both sexes.

• Toxicological Research
• /
• 제35권3호
• /
• pp.249-255
• /
• 2019

Cadmium is a strong toxic heavy metal which presents in paints and liquid wastes and causes oxidative stress in fish. On the other hand, lead is widely used for different purposes, e.g. lead pipes, it targets vital organs such as liver and kidney causing biochemical alterations. The present study evaluates the effects of 60 days exposure to Cd and Pb either single or combined together in African catfish. Sixty-four fishes were divided into 3 groups and exposed to $CdCl_2$ (7.02 mg/L) or $PbCl_2$ (69.3 mg/L) or a combination of them along with control group. Activities of acid phosphatase (ACP), lactate dehydrogenase (LDH) and glucose-6-phosphate dehydrogenase (G-6-PDH) were estimated. Moreover, gill, liver and kidney were assayed for activities of superoxide dismutase (SOD), catalase (CAT) and levels of glutathione (GSH) and malondialdehyde (MDA). Individual exposure showed that both Cd and Pb significantly decreased LDH activity and SOD activity in the kidney. Pb significantly increased G-6-PDH activity and decreased GSH level in the gill. CAT activity in liver and kidney elevated significantly on Cd exposure while lead caused a significant depletion in the liver and significant elevation in the kidney. Both Cd and Pb significantly increased MDA levels in liver and kidney while Pb increased its level in gills. The combined exposure resulted in normalization of LDH, G-6-PDH activity, and CAT activity in liver and kidney as well as GSH level in both tissues and MDA in gill and kidney. The combination increased SOD activity and MDA level in liver and decreased SOD activity in kidney and GSH level in gills. In conclusion, the antioxidant system of African catfish was adversely affected by prolonged exposure to Cd and Pb. The combined exposure caused less damage than individual exposure and returned most parameters to those of controls.

• Toxicological Research
• /
• 제25권4호
• /
• pp.209-216
• /
• 2009

We have recently reported that the continuous exposure of rats to a concrete building environment under cool temperatures had adverse effects on general health parameters and embryo-fetal development. This study examined to compare the potential effects of concrete and wood building environments on pregnant dams and embryo-fetal development in rats. Groups of 10 mated females were exposed to polycarbonate (control), concrete, or wood cages from gestational days (GD) 0 to 20 under cool temperatures $(11.9\sim12.3^{\circ}C)$. All the females underwent a caesarean section on GD 20, and their fetuses were examined for any morphological abnormalities. The temperatures in the cages were similar in all groups but the relative humidity in the concrete and wood groups were higher than in the control group. The concentration of volatile organic compounds in the wood group was higher than in the control group. In the concrete group, maternal effects manifested as an increase in the incidence of clinical signs, a lower body weight, and a decrease in the thymus and ovary weights. Developmental effects included increased post-implantation loss and decreased litter size. Infrared thermal analysis showed that the skin temperature of the rats in the concrete group was lower than that in the control group. In contrast, there were no exposure-related adverse effects on the maternal and developmental parameters in the wood group. Overall, the exposure of pregnant rats to a concrete building environment under cool temperatures has adverse effects on the clinical signs, body weight, skin temperature, organ weight, and embryo-fetal development. On the other hand, exposure to a wood building environment does not have any adverse effects in rats.

• Toxicological Research
• /
• 제26권1호
• /
• pp.67-74
• /
• 2010

The present study was conducted to obtain information on the effects of amitraz on reproductive and developmental parameters in rats. The test chemical was administered via the drinking water containing 0, 40, 120, and 360 ppm to male rats from 2 weeks before mating to the end of 14-day mating period and to females from 2 weeks before mating, throughout mating, gestation and up to lactational day 4. During the study period, clinical signs, body weights, food intake, organ weights, reproductive and littering findings, necropsy findings, sperm parameters, and histopathology were examined. At 360 ppm, decreases in the body weight gain, food consumption, and the number of live pups and an increase in the post-implantation loss were observed. In addition, decreases in the seminal vesicle weight and sperm motility were found in males. At 120 ppm, a decrease in the food consumption was found transiently in both males and females, but no reproductive and developmental toxicity was observed in both sexes. There were no signs of either general or reproductive and developmental toxicity in the 40 ppm group. Based on these results, it was concluded that the repeated oral administration of amitraz to rats resulted in a decrease in the food consumption at 120 ppm and decreases in the seminal vesicle weight, sperm motility, and the number of live pups and an increase in the post-implantation loss at 360 ppm in rats. Under these experimental conditions, the no-observed-adverse-effect level (NOAEL) of amitraz for general and reproduction/developmental toxicity was believed to be 120 ppm, and the no-observed-effect level (NOEL) of amitraz was believed to be 40 ppm in rats.

• Toxicological Research
• /
• 제24권4호
• /
• pp.273-280
• /
• 2008

The single intratracheal instillation (ITI) of bleomycin (BLM) is a widely used method for inducing experimental pulmonary fibrosis in rat model. In the present study, pulmonary function tests (PFTs) of tidal volume ($V_T$), minute volume ($V_M$), and respiratory frequency ($F_R$) have been applied to study their possibility as a tool to monitor the progress of BLM-induced lung injury in rat model. Rats were treated with a single ITI of BLM (2.5 mg/kg) or saline (control). Animals were euthanized at 3, 7, 14, 21, and 28 days post-ITI. Lung toxicity effects were evaluated by inflammatory cell count, lactate dehydrogenase (LDH) activity in the bronchoalveolar lavage fluid (BALF), and light microscopic examination of lung injury. The PFT parameters were measured immediately before the animals were sacrificed. BLM treatment induced significant cellular changes in BALF-increase in number of total cells, neutrophils, and lymphocytes along with sustained increase in number of macrophages compared to the controls at days 3, 7, and 14. BALF LDH level was significantly increased compared to that in the controls up to day 14. On day 3, infiltration of neutrophils was observed in the alveolar spaces. These changes developed into marked peribronchiolar and interstitial infiltration by inflammatory cells, and extensive thickening of the interalveolar septa on day 7. At 14, 21, and 28 days, mild peribronchiolar fibrosis was observed along with inflammatory cell infiltration. The results of PFT show significant consistencies compared to the results of other toxicity tests. These data demonstrate that the most suitable time point for assessing lung fibrosis in this model is 14 days post-ITI of BLM based on the observation of fibrosis at 14, 21, and 28 days. Further, the progress of lung injury can be traced by monitoring the PFT parameters of $F_R$, $V_T$, and $V_M$.

• Toxicological Research
• /
• 제24권2호
• /
• pp.119-127
• /
• 2008

The objectives of this study were to examine the lung injury and inflammation caused by manual metal arc stainless steel(MMA-SS) welding fume inhalation and to evaluate the recovery process. Sprague-Dawley rats were exposed to MMA-SS welding fumes for 2 h per day in a whole-body exposure chamber, with a total suspended particulate(TSP) concentration of $51.4{\pm}2.8mg/m^3$(low dose) or $84.6{\pm}2.9mg/m^3$(high dose) for 30 days. The animals were sacrificed after 30 days of exposure as well as after a 30-day recovery period. To assess the inflammatory or injury responses, cellular and biochemical parameters as well as cytokines were assayed in the bronchoalveolar lavage fluid(BALF). MMA-SS welding fume exposure led to a significant elevation in the number of alveolar macrophages(AM) and polymorphonuclear cells(PMN). Additionary, the values of $\beta$-n-acetyl glucosaminidase($\beta$-NAG) and lactate dehydrogenase(LDH) in the BALF were increased in the exposed group when compared to controls. After 30 days of recovery from exposure, a significant reduction in inflammatory parameters of BALF was observed between the exposed and recovered groups. Slight, but significant elevations were noted in the number of AM and PMN in the recovered groups, and AM that had been ingested fume particles still remain in the lungs. In conclusion, these results indicated that welding fumes induced inflammatory responses and cytotoxicity in the lungs of exposed rats. Fume particles were not fully cleared from lungs even after a 30-day recovery period.

• Toxicological Research
• /
• 제33권3호
• /
• pp.239-253
• /
• 2017

Neodymium is a future-oriented material due to its unique properties, and its use is increasing in various industrial fields worldwide. However, the toxicity caused by repeated exposure to this metal has not been studied in detail thus far. The present study was carried out to investigate the potential inhalation toxicity of nano-sized neodymium oxide ($Nd_2O_3$) following a 28-day repeated inhalation exposure in male Sprague-Dawley rats. Male rats were exposed to nano-sized $Nd_2O_3-containing$ aerosols via a nose-only inhalation system at doses of $0mg/m^3$, $0.5mg/m^3$, $2.5mg/m^3$, and $10mg/m^3$ for 6 hr/day, 5 days/week over a 28-day period, followed by a 28-day recovery period. During the experimental period, clinical signs, body weight, hematologic parameters, serum biochemical parameters, necropsy findings, organ weight, and histopathological findings were examined; neodymium distribution in the major organs and blood, bronchoalveolar lavage fluid (BALF), and oxidative stress in lung tissues were analyzed. Most of the neodymium was found to be deposited in lung tissues, showing a dose-dependent relationship. Infiltration of inflammatory cells and pulmonary alveolar proteinosis (PAP) were the main observations of lung histopathology. Infiltration of inflammatory cells was observed in the $2.5mg/m^3$ and higher dose treatment groups. PAP was observed in all treatment groups accompanied by an increase in lung weight, but was observed to a lesser extent in the $0.5mg/m^3$ treatment group. In BALF analysis, total cell counts, including macrophages and neutrophils, lactate dehydrogenase, albumin, interleukin-6, and tumor necrosis factor-alpha, increased significantly in all treatment groups. After a 4-week recovery period, these changes were generally reversed in the $0.5mg/m^3$ group, but were exacerbated in the $10mg/m^3$ group. The lowest-observed-adverse-effect concentration of nano-sized $Nd_2O_3$ was determined to be $0.5mg/m^3$, and the target organ was determined to be the lung, under the present experimental conditions in male rats.

• Toxicological Research
• /
• 제17권3호
• /
• pp.187-194
• /
• 2001

The oxidative stress causes the cell damage and death and thereby, stimulates membrane lipid peroxidation. In this study, the correlation between the lipid peroxidation product and the parameter of liver fibrosis (cirrhosis) was investigated in cholestasis induced rats. The Sprague-Dawley rats were divided into 3 groups (sham: sham operation, BDL/S-I and BDL/S-II : bile duct ligation/scission) and were observed for 2 or 4 weeks. After observation period, the organs were weighed and the ratio of organ weight/body weight was calculated. Sera and liver tissue were used for the measurement of malondealdehyde (MDA), parameter of clinical biochemistry, total collagen content and the staining. The ratio of organ weight/body weight in BDL/S-I and BDL/S-II was significantly increased compared to sham operated group. Serological parameters (Alanine transaminase, Aspartate transaminase, Alkaline phosphatase and Total bilirubin) in BDL/S-I and BDL/S-II group were significantly higher than those in sham operated group. Concentration of MDA in BDL/S-I (261%) and BDL/S-II(790%) was significantly increased compared to MDA in sham operated group. And the content of hydroxyproline (hyp) in BDL/S-I and BDL/S-II group was significantly increased 2~4 times than in sham operated group. The good correlations between hyp in liver tissue and MDA in sera of sham operated group and all operated group were found (r=0.825). The significantly higher value of MDA, hyp and serological parameters in BDL/S-I and BDL/S-II group suggests the stimulation of lipid peroxidation and chronic liver damage. Especially the activation of lipid peroxidation and the stimulation of liver fibrosis was stronger in BDL/S-II group than in BDL/S-I group. The stronger fibrosis, portal-portal septum formation, the more massive bile duct proliferation in portal triads and stroma, and hepatocytes swelling were observed in liver tissue of and BDL/S-II group compared to BDL/S-I group. Conclusively, a good correlation between MDA as a lipid peroxidation marker and hyp as a liver fibrotic parameter could be connected with the process of liver fibrosis. Moreover, cholestasis condition may cause jaundice, activation of lipid peroxidation, and collagen accumulation in liver. Additionally, optimal observation period of bile duct obstruction for the screening of antioxidant and antifibrotic effect in rats would be four weeks.

• Toxicological Research
• /
• 제28권4호
• /
• pp.279-288
• /
• 2012

Rats were administered zearalenone (ZEA) via gavage at dosages of 0, 1, 5, and 30 mg/kg for 36 days. On treatment day 8, inactivated porcine parvovirus vaccine (Vac) was injected intraperitoneally. Antibody production against porcine parvovirus was then measured as a function of ZEA treatment. Compared to the vaccine alone, ZEA treatment, with or without Vac, decreased the serum level of IgG. The level of IgM decreased in all ZEA groups at day 22, but the decrease was sustained only in the medium-dose ZEA group at day 36. The level of IgA was unchanged in the Vac only and ZEA groups at day 22, but was decreased in the 5 mg/kg ZEA plus Vac group compared to the Vac only group at day 36. The level of IgE was decreased by all doses of ZEA at day 22, but was unaffected in ZEA plus Vac groups compared to the Vac only group. The levels of IL-1 in the thymus and spleen; INF-${\gamma}$ in serum; IL-2, IL-6, and IL-10 in the thymus; and IL-10 and IFN-${\gamma}$ in the spleen decreased after ZEA administration. Furthermore, the levels of IL-$1{\beta}$ in the spleen and mesenteric lymph node, IL-$1{\beta}$ in the thymus, IL-2 in the thymus and spleen, IL-6 in the thymus, IL-10 and IFN-${\gamma}$ in the spleen, and GM-CSF and TNF-${\alpha}$ in the thymus decreased after vaccination in rats exposed to ZEA. In conclusion, these results suggest that ZEA exposure via drinking water can cause an immunosuppressive effect by decreasing immunoglobulins in serum and cytokines in lymphoid organs.