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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.
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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.
ABSTRACT
<p><b>OBJECTIVE</b>To 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.</p><p><b>METHODS</b>Forty 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.</p><p><b>RESULTS</b>Fourteen 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).</p><p><b>CONCLUSION</b>Gavaged 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.</p>