Objective: To assess the effects of subchronic intake of high-dose Dendrobium officinale on body weight, food intake, food utilization, and blood biochemical parameters in rats, so as to provide insights into assessment of edible safety of D. officinale. Methods: Eighty SPF-grade SD rats were randomly divided into the low-, medium- and high-dose groups and the control group, of 10 male and 10 female rats in each group. Rats in the low-, medium- and high-dose groups were administered with D. officinale feeds at doses of 2.0, 4.0, and 8.0 g/kg body weight, respectively, while animals in the control group were given basic diet for successive 13 weeks. The rat body weight, food intake, food utilization, and blood biochemical parameters were compared between groups. Results: Normal diet and activity was seen in all rats, and no abnormal syndromes, signs or deaths were found during the study. There were no significant differences in rat body weight, food intake, total weight gain, total food intake, alanine aminotransferase, aspartate aminotransferase, urea nitrogen, creatinine, triacylglycerol, cholesterol, total protein, albumin, albumin/globulin ratio or blood glucose among four groups (P>0.05). The food utilization 7 weeks post-administration [(8.71%±0.78%) vs. (10.54%±1.37%), P<0.05] and the total food utilization [(18.00%±0.41%) vs. (19.51%±1.21%), P<0.05] were significantly lower in male rats in the high-dose group than in the control group. Conclusion Subchronic intake of high-dose D. officinale shows no toxicity in rats, and reduced food utilization may be associated with the health function of D. officinale in male rats.

Objective: To detect the bioavailability of 21 types of perfluorochemicals (PFCs) in rat liver and to examine the effect of protein powder. Methods: Twenty-four rats of the SD strain were randomly divided into the control group, the model group, and the protein powder group. Twenty-one types of PFCs were mixed at an equal concentration of 10 ng/mL, and rats in the model group and the protein powder group were given by oral administration of PFCs mixtures at a daily dose of 5 mL/kg. Rats in the protein powder group were given protein powder by gavage at a dose of 15 mL/kg, while animals in the model and control groups were given deionized water at doses of 15 and 20 mL/kg for 28 successive days. The PFCs contents were quantified in rat liver using ultra-high performance liquid chromatography-electrospray tandem mass spectrometry (UPLC-MS/MS), and the bioavailability was estimated. Results: There were no significant differences in rat body weight or liver/body weight ratio in the control, model and protein powder groups (P>0.05). There were no significant differences in the bioavailability of perfluoroalkylated carboxylic acid (PFCA) or sulfonate (PFSA) in the liver of female and male rats between the protein powder group and the model group (P>0.05), and the gross bioavailability of PFCA (t=-22.266, P<0.001) and PFSA (t=-34.312, P<0.001) was significantly higher in the liver of male rats than in that of female rats in the model group, and the bioavailability of PFCA and PFSA increased followed by a reduction in rat livers with the increase of carbon chain length in the model group. In the model group, the highest bioavailability was measured in perfluorododecanoic acid (PFDoA) and sodium perfluorooctylsulfonate (L-PFOS) in the female rat liver [(36.06±2.93)% and (37.11±1.73)%], and the highest bioavailability was measured in perfluorononanoic acid (PFNA) and L-PFOS in the female rat liver [(61.02±2.16)% and (87.16±3.29)%]. Conclusions The bioavailability of PFCs correlates with the carbon chain length and animal gender in rat livers, and protein powder poses no clear-cut effects on the bioavailability of 21 types of PFCs in rat livers.

Objective : To study the damage effect of sunlight ultraviolet exposure on skin. Methods : No exposure group, low exposure group and high exposure group were set up with 10 mice in each. The exposure doses of sunlight ultraviolet were 0, 10 J/cm2 and 20 J/cm2, respectively. The skin of mice was irradiated by a sunlight ultraviolet simulator for 5 days a week, 13 weeks. At the end of the experiment, the skin appearance of mice was examined; the skin moisture, oil content, texture density, hydroxyproline ( HYP ), hyaluronic acid (HA), malondialdehyde ( MDA ), glutathione ( GSH ) and superoxide dismutase ( SOD ) activities were detected; and the skin tissue morphology, collagen fiber morphology and elastic fiber morphology were observed. Results : The skin appearance of mice in the no exposure group was normal; in the low exposure group, only one mouse had mild skin desquamation; in the high exposure group, the skin was loose and wrinkled, dry and desquamated, local thickening and erythema formation. Compared with the no exposure group, the contents of skin moisture, HYP, HA and SOD activity were lower, texture density, MDA content, morphological scores of skin tissue, collagen fiber tissue and elastic fiber tissue were higher in the high exposure group ( all P<0.05 ). Compared with the low exposure group, the HA content and SOD activity were lower, the skin texture density, MDA content, and histomorphological scores of skin tissue and collagen fibers were higher in the high exposure group ( all P<0.05 ). Conclusion Exposure to 20 J/cm2 sunlight ultraviolet can significantly lead to abnormal skin appearance and function in mice.

Objective: To explore the effects of protein powder on the bioavailability of perfluoroalkyl substances (PFASs) in blood and kidneys of rats and renal function change. Methods: Twenty-four rats of the SD strain were randomly divided into the negative control group, PFASs group and protein powder group, with 8 rats (half males and half females) in each group. PFASs included 13 perfluorocarboxylic acids (PFCAs) and 8 perfluorosulfonic acids (PFSAs), and the mixture was used as a test subject for intervention. The rats in the negative control group were given deionized water at doses of 20 mL/kg·bw, in the PFASs group were given 5 mL/kg·bw of PFASs mixtures and 15 mL/kg·bw of deionized water, and in the protein powder group were given 5 mL/kg·bw of PFASs mixtures and 15 mL/kg·bw of protein powder (0.258 g/mL). After intervention for 28 successive days, body weight and kidney mass were weighed, and the kidney volume index was calculated. Serum creatinine and blood urea nitrogen were detected by an automatic biochemical analyzer. The PFCAs, PFSAs and PFASs contents were quantified in blood and kidney using ultra-high performance liquid chromatography-electrospray tandem mass spectrometry, and the bioavailability was estimated. Results: There was no significant differences in kidney mass, kidney volume index, serum creatinine and blood urea nitrogen among the negative control group, PFASs group and protein powder group (all P>0.05). The bioavailability of blood PFCAs, PFSAs and PFASs in the protein powder group was not significantly different from the PFASs group (all P>0.05). Compared with the PFASs group, the bioavailability of PFCAs, PFSAs and PFASs were significantly increased in kidneys of male rats in the protein powder group (all P<0.05), while were not significant different in those of female rats (all P>0.05). Conclusion Protein powder at the dose of this study can significantly improve the bioavailability of PFASs in kidneys of male rats, while there no obvious effects on the bioavailability of blood PFASs and renal function.

Objective: To study the effects of Lycium barbarum polysaccharides ( LBP ) on blood indexes and liver tissue morphology in rats with intrahepatic cholestasis. Methods: Sprague-Dawley rats were randomly divided into the control group, the model group, and LBP low, medium and high dose group. The rats in the model group and LBP dose groups were given 60 mg/kg alpha-naphthylisothiocyanate ( ANIT ) by gavage every three days of the experiment, and the rats in the control group were given salad oil instead of ANIT. From the third day, the rats in each dose group were given 40, 150 and 600 mg/kg LBP, and the rats in the model group were given distilled water. After four weeks, the blood and urine indexes were measured, and the morphological changes of liver tissue were observed. Results: From the third day of the experiment, the activity of rats in the model group and LBP dose groups decreased, and the color of urine changed to dark yellow. There was no abnormality in the group. In the model group, the levels of serum total bilirubin, direct bilirubin, total bile acid ( TBA ), alkaline phosphatase ( ALP ), γ-glutamyltransferase(γ-GGT), cholesterol, alanine aminotransferase ( ALT ), aspartate aminotransferase ( AST ), white blood cell ( WBC ), percentage of granulocyte, urinary bilirubin, urinary bile acid, liver mass and liver to body ratio were higher than those in the control group, while red blood cell and percentage of lymphocyte were lower than those in the control group ( all P<0.05 ). Pathological changes of liver tissue were observed. The levels of serum TBA, ALP, γ-GGT, ALT, AST, WBC and liver to body ratio in LBP high dose group were lower than those in the model group ( all P<0.05 ). The infiltration of inflammatory cells, proliferation and expansion of bile duct, degeneration and necrosis of liver cells were alleviated. Conclusions LBP can improve the blood indexes and pathological changes of liver tissue in rats with intrahepatic cholestasis at the dosage of 600 mg/kg. Inhibition of inflammatory response and reduction of oxidative stress injury may be the mechanism for alleviating cholestatic liver injury.

Objective: To observe the effect of 5-hudroxymethyl-2-furfural (5-HMF) on glycolipid metabolism and hepatic function in mice with type 2 diabetes mellitus (T2DM) and hepatic injury. Methods: A low, a medium and a high 5-HMF dose group, a model group, and a control group were designed, with ten female ICR mice in each group. The low, medium and high dose group were given 0.27, 0.80 and 2.67 mg/kgbw 5-HMF, respectively, for 12 weeks; while the model group and the control group were given volume controlled deionized water. The model group and three dose groups were fed with high-fat and high-sugar food (36%), and the intraperitoneal injection of alloxan (60 mg/kgbw) was executed in the 10th and 11th week; the control group were fed with normal food. The body weight, blood glucose, blood lipid, and liver function of mice were determined regularly. The livers were stained by periodic acid Schiff and the changes in pathology were observed. Results: Compared with the control group, the serum levels of glucose (GLU), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) were significantly higher in the model group (P<0.05). Compared with the model group, the AST level in the low and high 5-HMF dose group, and the LDH level in the low, medium and high 5-HMF dose group, were significantly lower (P<0.05). There were no significant differences in the levels of GLU, total cholesterol, LDL-C, triacylglycerol, HDL-C and ALT between the model group and the three dose groups (P>0.05). Moderate to severe vacuolar degeneration was observed in the model group, while mild vacuolar degeneration was observed in the high dose group. Medium or large amount of hepatic glycogen granules were observed in the high dose group and the model group. Conclusion Under the conditions of this experiment, 5-HMF does not show any obvious function of reducing blood glucose and lipid in the mice with T2DM and liver injury, but show some protective effects on liver function．

Objective: To evaluate the toxicological safety of a compound Chinese medicine preparation of gardenia. Methods: Eighty healthy SD rats with half males and half females were randomly divided into four groups. The low-,moderate- and high-dose group were given 1.00 g/kgbw,2.00 g/kgbw and 4.00 g/kgbw of the preparation,while the control group was given distilled water,by gavage for 30 days. The changes of diet,weight,hematological parameters and major organs of rats were observed,and the histopathological examination of the main organs was performed. Results: The rats in the high-dose group reduced activities and their urine turned dark yellow or green,while the other rats showed no abnormality. No rats died during the experimental period. Compared with the control group,the weight,the total weight gain,the food utilization rate,the fasted weight of the rats in the high-dose group and the hemoglobin content of the female rats in the high-dose group were significantly decreased（P<0.05）;the ratio of liver to body weight,the ratio of kidney to body weight,the serum creatinine levels of the rats in the high-dose group and the serum urea nitrogen levels of the male rats in the high-dose group were significantly higher（P<0.05）. The livers and kidneys of the rats in high-dose group turned different degrees of dark green;the hepatic pigmentation,hepatocyte vacuolar degeneration,bile duct hyperplasia accompanied with inflammatory cell infiltration,renal pigmentation,renal tubular epithelial cellular swelling,and renal interstitial inflammatory cell infiltration were observed. Conclusion This preparation at a dose of 4.0 g/kgbw has hepatotoxicity and nephrotoxicity to rats. A dose of 2.0 g/kgbw has no harmful effect but less than 100 times of the possible human intake,the safety is not guaranteed.

Objective : To evaluate the health effects of persistent organic pollutants（POPs）on body weight,food intake,internal organs,blood biochemistry,metabolic enzymes and antioxidant ingredients of rats. Methods : Sixteen healthy Sprague-Dawley（SD）rats were randomly divided into the experimental group exposed to 10 mL/kg mixture of POPs（10 ng/mL PCBs,5 ng/mL PBDEs,1 ng/mL PCDD/F）everyday for 28 days by gavage,and the control group exposed to the same volume of soybean oil in the same way. Body weight and food intake of the rats were recorded regularly;blood routine and biochemical indices were detected;liver,kidney,spleen and testicles（ovary）of the rats were weighed to calculate organ coefficients;metabolic enzymes and antioxidant ingredients were detected from livers of the rats. Results : No obviously abnormal symptoms and no deaths were found in both groups. Compared to the control group,the weekly food intake in the experimental group increased more for there was an interaction between grouping and time（P< 0.05）. The ratio of liver to body weight of male rats in the experimental group was higher than that in the control group [（3.87± 0.19）% vs.（3.53± 0.06）%,P< 0.05]. The haemoglobin and red blood cell of female rats in the experimental group were lower than those in the control group[（145.25± 6.18）g/L vs.（154.50± 4.20）g/L;（6.90± 0.14）× 1012/L vs.（7.39± 0.24）× 1012/L;both P< 0.05]. The glutathione-S-transferase（GST）of female rats in the experimental group was higher than that in the control group [（13.37± 1.05）U/mgprot vs.（9.43± 1.08）U/mgprot,P< 0.05]. The cytochrome P4501A1of rats in the experimental group was higher than that in the control group [female：（88.23± 5.81）ng/mgprot vs.（73.85± 5.86）ng/mgprot;male：（96.80± 13.32）ng/mgprot vs.（ 72.20± 2.01）ng/mgprot;both P< 0.05]. Conclusion After exposed to low dose of POPs,the cytochrome P4501A1 increased in all rats,the liver to body weight ratio increased in male rats,GST activity increased while red blood cell and haemoglobin decreased in female rats,which indicated possible body damages in rats.

Objective: To learn the toxicity of Dendrobium officinale flowers to pregnant rats ( P, F1 ) and offspring rats ( F1, F2 ) before birth, so as to provide toxicological evidence for the safety assessment. Methods : The rats were divided into four groups with 20 female rats and 10 male each. The rats in three dose groups were fed with Dendrobium officinale flowers at the dose of 2.0, 4.0, 6.4g/kgbw. After two generation, the F1a and F2a rats were fed with basal diet; F1b and F2b rats were fed with Dendrobium officinale flowers. The body weights and total weight gains during the gestation, the conception rates, the pregnancy rates, the birth weights and survival rates of offspring rats were examined. Results: There were no statistically significant differences in the body weights and total weight gains during the gestation, the conception rates, and the pregnancy rates in pregnant rats ( P, F1 ) among the four groups ( P>0.05 ). There were also no statistically significant differences in the survival rates and live birth rates in offspring rats (F1, F2) between the dose groups and the control group ( P>0.05 ). Conclusions Dendrobium officinale flowers did not show obviously adverse effects on pregnant rats ( P, F1 ) and offspring rats ( F1, F2 ) before birth.

OBJECTIVETo investigate the toxicity of intragastrically administered N, N-dimethylformamide (DMF) in female Wistar rats, and to provide experimental data for the overall evaluation of DMF toxicity under different ways of exposure.

METHODSForty female Wistar rats weighing 150∼180 g were randomly divided into four groups: control group (treated with water) and three DMF exposure groups with doses of 50 mg/kg, 100 mg/kg, and 200 mg/kg. After oral administration of DMF once a day for 14 consecutive days, the rats were weighed and sacrificed. The liver, kidney, brain, and uterus were weighed to calculate organ indices. The pathological changes in the liver were examined by HE staining. The protein expression of HSP70 in the liver, kidney, and brain was determined. Finally, peripheral lymphocytes were collected from the arteria cruralis to determine DNA damage by comet assay.

RESULTSFourteen days after DMF exposure, the body weight and organ indices of the kidney, brain, and uterus showed no significant changes. However, the liver index showed concentration-dependent increase in all DMF exposed groups (3.52±0.21, 3.55±0.13, and 3.88±0.22 in the low-, medium-, and high-dose groups, respectively), as compared with the control group (3.24±0.28) (P < 0.05 or P < 0.01). The pathological damage in the liver also showed a concentration-dependent manner. Inflammatory cell infiltration and granular degeneration in centrilobular hepatocytes were observed in the high-dose group. No significant change in protein expression of HSP70 was observed in the liver, kidney, or brain of DMF-exposed rats (P > 0.05). DNA damage was induced by DMF, and the DNA percentage of lymphocyte comet tail, average tail length, and tail moment in exposed groups were all significantly increased as compared with the control group (P < 0.05 or P < 0.01).

CONCLUSIONGavaged DMF can induce liver injury and DNA damage in lymphocytes in rats 14 days after administration. There is no significant change in protein expression of HSP70 in the liver, brain, or kidney after DMF exposure.

Animals ; Brain ; drug effects ; pathology ; DNA Damage ; drug effects ; Dimethylformamide ; toxicity ; Female ; Gastric Lavage ; HSP70 Heat-Shock Proteins ; metabolism ; Kidney ; drug effects ; pathology ; Liver ; drug effects ; pathology ; Lymphocytes ; drug effects ; Rats ; Rats, Wistar ; Toxicity Tests