BackgroundTinospora sagittata (Oliv.) Gagnep. var. craveniana (S.Y.Hu) Lo (TSG) is a traditional Chinese herb that has been used for the treatment of upper respiratory tract infection and has anti-bacterial and anti-ulcer activity. Our study investigated the bactericidal effects of TSG and its major component, palmatine, against a Helicobacter pylori (H. pylori) strain isolated from pig and the standard strain H. pylori SS1 in vitro and in vivo.MethodsH. pylori was isolated from pig and named H. pylori SCYA201401. For in vitro experiments, the inhibitory activity of TSG and palmatine against H. pylori SCYA201401 and H. pylori SS1 were tested by use of the agar cup diffusion technique. The minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) were determined from the absence of H. pylori colonies on agar plates. Time-kill curves were used to evaluate bactericidal activity; the average number of colonies was calculated at 0 to 48 h after liquid incubation, with concentrations of drugs at 0.5, 1, and 2 × MIC. For in vivo experiments, H. pylori SCYA201401-infected mice were randomly divided into TSG, palmatine, triple therapy (omeprazole, clarithromycin, and amoxicillin), blank control, and model groups. The eradication ratios were determined by use of rapid urease tests and bacterial culture.ResultsIn vitro, the MIC and MBC of TSG against H. pylori SCYA201401 and SS1 were both 6250 μg/mL, whereas palmatine against H. pylori SCYA201401 was 6.25 μg/mL and against H. pylori SS1 was 3.12 μg/mL. The time-kill curves showed a dose-dependent, progressive decline in the numbers of viable bacteria up to 40 h. In vivo, the eradication ratios in the TSG and palmatine groups of mice were 80 and 50 % compared with 70 % in the triple-therapy group.ConclusionTSG and its major component, palmatine, have bactericidal activity against H. pylori in vitro and in vivo. The possibility that TSG or palmatine can be effective in the treatment of human and animals H. pylori infection deserves investigation.
Zinc oxide (ZnO) is widely incorporated as a food additive in animal diets. In order to optimize the beneficial effects of ZnO and minimize any resultant environmental pollution, ZnO nanoparticles are often used for delivery of the zinc. However, the possible toxic effects of ZnO nanoparticles, including effects on cytochrome P450 (CYP450) enzymes, have not been evaluated. In this study, we investigated the effect of ZnO nanoparticles, in doses used in animal feeds, on CYP450 enzymes, liver and intestinal enzymes, liver and kidney histopathology, and hematologic indices in rats. We found that liver and kidney injury occurred when the concentrations of ZnO nanoparticles in feed were 300–600 mg/kg. Also, liver mRNA expression for constitutive androstane receptor was suppressed and mRNA expression for pregnane X receptor was induced when feed containing ZnO nanoparticles was given at a concentration of 600 mg/kg. Although the expression of mRNA for CYP 2C11 and 3A2 enzymes was induced by ZnO nanoparticles, the activities of CYP 2C11 and 3A2 were suppressed. While liver CYP 1A2 mRNA expression was suppressed, CYP 1A2 activity remained unchanged at all ZnO nanoparticle doses. Therefore, it has been concluded that ZnO nanoparticles, in the doses customarily added to animal feed, changed the indices of hematology and blood chemistry, altered the expression and activity of hepatic CYP enzymes, and induced pathological changes in liver and kidney tissues of rats. These findings suggest that greater attention needs to be paid to the toxic effects of ZnO nanoparticles in animal feed, with the possibility that the doses of ZnO should be reduced.
BackgroundJinqing granules which are made of a mixture extract that contains Radix Tinosporae and Canarii fructus in proportions according to a longstanding formula have a good effect on the prevention and treatment of gastric ulcer disease. It has not been through safety through systematic toxicological studies, however. To provide basis for clinical application, we performed safety pharmacology and subchronic toxicity experiments in specific pathogen-free Sprague-Dawley rats.ResultsIn safety pharmacology experiments, Jinqing granules had no evident adverse effects on the central nervous, cardiovascular, or respiratory systems. In subchronic toxicity study, 2–8 g/kg of Jinqing granules induced no evident adverse effects on Clinical signs, body weight changes, food and water intake, death daily, indicators of urine, hematological assay, serum biochemistry, organ coefficient and histopathological examination. However, the 16 g/kg dose was associated with slightly slowed weight growth, decreased number of sperm in seminiferous tubules and increased values of serum aspartate aminotransferase and bilirubin. During the 30-day feeding test, 3 rats that received the 16 g/kg dose died, but the deaths were most likely due to trauma of oral gavage, not to drug toxicity.ConclusionJinqing granules given to Sprague-Dawley rats orally for 30 days at a dose of 8 g/kg or less appears safe, but higher doses were not proven safe. The significance of these observations with respect to animal usage of Jinqing granules deserves thorough investigation.
Formaldehyde (FA) is an occupational and indoor pollutant. Long-term exposure to FA can irritate the respiratory mucosa, with potential carcinogenic effects on the airways. The effects of acute FA poisoning on the activities of CYP450 isoforms CYP1A2, CYP2C11, CYP2E1, and CYP3A2 were assessed by determining changes in the pharmacokinetic parameters of the probe drugs phenacetin, tolbutamide, chlorzoxazone, and testosterone, respectively. Rats were randomly divided into three groups: control, low FA dose (exposure to 110 ppm for 2 h for 3 days), and high FA dose (exposure to 220 ppm for 2 h for 3 days). A mixture of the four probe drugs was injected into rats and blood samples were taken at a series of time points. Plasma concentrations of the probe drugs were measured by HPLC. The pharmacokinetic parameters t1/2, AUC(0−t), and Cmax of tolbutamide, chlorzoxazone, and testosterone increased significantly in the high dose versus control group (P < 0.05), whereas the CL of chlorzoxazone and testosterone decreased significantly (P < 0.05). However, t1/2, AUC(0−t), and Cmax of phenacetin decreased significantly (P < 0.05), whereas the CL of phenacetin increased significantly (P < 0.05) compared to controls. Thus, acute FA poisoning suppressed the activities of CYP2C11, CYP2E1, and CYP3A2 and induced the activity of CYP1A2 in rats. And the change of CYP450 activity caused by acute FA poisoning may be associated with FA potential carcinogenic effects on the airways.
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