Protective effect of Diyarbak?r watermelon juice on carbon tetrachloride-induced toxicity in rats

The present study was designed to evaluate the effect of Diyarbak?r watermelon (Citrullus lanatus cv. Sürme) juice on lipid peroxidation states in rat liver, kidney and brain. In vivo administration of carbon tetrachloride (CCl₄) once a week for 28 days caused a significant elevation of serum markers of liver damage, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total bilirubin (TB) and decrease in albumin when compared to the control group. However, administration of carbon tetrachloride along with watermelon juice or ursodeoxycolic acid (UDCA) significantly reduces these changes. Increased lipid peroxide (LPO) level was observed in the liver, kidney and brain tissues after CCl₄ administration. However, watermelon juice and UDCA treatment prevented the increase in LPO. The results indicated that watermelon juice protects the liver, kidney and brain tissues from experimental CCl₄ toxicity in rats and that the protective effect of watermelon juice may be due to its antioxidant activity and inhibition of lipid peroxide formation. In conclusion, present study reveals biological evidence that supports the use of watermelon juice in the treatment of chemical-induced hepatotoxicity.     

Protective effect of fermented sea tangle against ethanol and carbon tetrachloride-induced hepatic damage in Sprague–Dawley rats

Sea tangle has long been used as Korean folk remedy to promote material health, and is one of the popular dietary supplement. This study was designed to evaluate the protective effect of fermented sea tangle (FST) against ethanol and carbon tetrachloride (CCl₄)-induced hepatotoxicity in rats. Sprague–Dawley rats were orally treated with FST (25, 250, 2500 mg/kg/day) with administration of ethanol (5 mL/kg) for 13 weeks and the single intraperitoneal (i.p.) dose of 50% CCl₄ (5 mL/kg/day, CCl₄ in olive oil) at 12 week, and repeated i.p. dose of 20% CCl₄ (2 mL/kg/day) for 1 week. Hepatotoxicity was evaluated by measuring the serum levels of glutamic pyruvate transaminase (GPT), gamma glutamyl transpeptidase (γ-GT) and malondialdehyde (MDA) as well as the tissue levels of antioxidant enzyme such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). Ethanol and CCl₄-induced the rat liver damage, and significantly increased (p < 0.05) the GPT, γ-GT and MDA levels, and decreased the SOD, CAT and GPx levels. However, treatment with FST could decrease serum GPT, γ-GT, and MDA levels significantly in plasma, and increase the activities of SOD, CAT, and GPx in liver tissues compared with ethanol and CCl₄-treated group.     

Antagonistic effect of quninuclidinyl-benzilate on nicotine-induced convulsions in mice

<正> Quninuclidinyl-benzilate (QNB) has long been recognized as a competitive antagonist of muscarinic acetylcholine receptors, while its effects on brain nicotinic acetylcholine receptors were not examined. The results of our preliminary experiments indicated that iv QNB in rats could prevent EEG seizures induced by nicotine 1.0 mg/kg iv. The purpose of this experiment is to examine the effects of QNB on brain nicotinic acetylcholine receptors. Intravenous injection of QNB COHld dose-dependcrltly prevent both behavioral convulsio/is and clonic—tonjc EEG-seizure discharges indaced by nicotine base at the dose of 1.0 mg/kg iv in mice.ED_(50)±CL_(95)=2.0±0.6mg/kgiv,b±S_b=2.8±0.5,r=0.94.The ED_(50) of QNB against nicotine-convulsions was twenty times of that of     

Enhanced effect of κ-carrageenan on TNBS-induced inflammation in mice

BackgroundAs a sulfated polysaccharide, carrageenan has been widely used as common food additive.MethodsIn the present study, we investigated the effects of κ-carrageenan on TNBS-induced gut inflammation in mice. BALB/c mice were pretreated with κ-carrageenan for 14 days prior to the administration of TNBS.ResultsOur results showed that κ-carrageenan pretreatment aggravated the loss of body weight and further increased the mortality rate. Histological and morphological analyses revealed that the TNBS-induced colonic inflammation was deteriorated by the κ-carrageenan administration. The ratio of CD4⁺ CD25⁺ CD127dim/CD4⁺ of the κ-carrageenan + TNBS groups was significantly lower than that of the TNBS group. The expression of IL-2, TNF-α and IL-6 was significantly increased, whereas the expression of IL-10 was significantly decreased in the κ-carrageenan + TNBS groups. In addition, κ-carrageenan, together with TNBS, decreased the enzyme activity of SOD and GSH-px and up-regulated the expression of TLR4, NF-κB, p-ERK, p-JNK, p-Jun., IL-8 and MDA in the colonic mucosa.Conclusionsκ-Carrageenan aggravated the TNBS-induced intestinal inflammation, and such an effect could be associated with the oxidative stress and activation of TLR4-NF-κB and MAPK/ERK1/2 pathway.     

Inhibitory effect of β-sitosterol on TNBS-induced colitis in mice

β-Sitosterol, a common sterol in herbal medicines, exhibits anti-inflammatory effects beneficial in the treatment of lung inflammation, asthma, and bronchospasm. To evaluate whether β-sitosterol also has anticolitic benefits, we tested the effect of β-sitosterol on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice. β-Sitosterol inhibited colon shortening and led to lowered macroscopic scores and myeloperoxidase activity in TNBS-treated colitic mice. β-Sitosterol also inhibited the expression of proinflammatory cytokines TNF-α, IL-1β, and IL-6, and an inflammatory enzyme, cyclooxygenase (COX)-2, in the colons of TNBS-induced colitic mice, as well as the activation of NF-κB. Based on these findings, β-sitosterol may ameliorate colitis by inhibiting the NF-κB pathway.     

Anticonvulsive effect of agmatine in mice

AIM: The present study was designed to examine the effect of agmatine, the decarboxylated product of L-arginine by L- arginine decarboxylase, on convulsion in the mouse maximal electroshock (MES) test and mouse glutamate-induced convulsion test. METHODS: MES convulsion and glutamate convulsion were respectively induced by an electrical stimulation     

Effect of a novel phosphodiesterase type 5 inhibitor,CPD1, on carbon tetrachloride-induced liver fibrosis in mice北大核心CSCD

Aim To investigate the effects of CPD1, a novel phosphodiesterase 5 inhibitor, on liver pathological phenotype and hepatic stellate cells (HSCs) activation in hepatic fibrosis model mice caused by carbon tetrachloride ( CCl4). Methods Male C57BL/6 J mice were divided into four groups randomly ( control group, CCl4group, CCl4+ CPD1 group and CCl4+ tadalafil group) . Hepatic fibrosis model was construc¬ted by intraperitoneal injection of CCl4( twice a week) . Four weeks after CCl4injection, the mice were treated with CPD1 (2 mg kg-1• d-1) , or Tadalafil (10 mg • kg-1• d-1) by intragastric administration, respec¬tively, for four weeks. Hematoxylin-eosin staining and Sirius Red staining were used to observe the distribu¬tion of liver tissue structural lesions and fibrosis. Im-munohistochemical staining was used to detect the ex¬pression of a-smooth muscle actin ( a-SMA) and fi-bronectin. Results Compared with control group, the liver tissue structure was seriously damaged in CCl4group with many hepatocytes necrosis and inflammatory cell infiltration, indicating that liver injury occurred in the CCl4-induced hepatic fibrosis model mice. Moreo¬ver, the expressions of a-SMA increased significantly in CCl4group. Compared to CCl4group, the liver tissue damage was significantly improved in PDE5 inhibitors group,most notably, CPD1 had a better curative effect than tadalafil did. Furthermore, CPD1 inhibited the ex¬pression of a-SMA markedly and reduced the expres-sion of ECM-related proteins induced by transforming growth factor pi ( TGF-f31 ) in Lieming Xu-2 ( LX-2 ) cells. Conclusions Phosphodiesterase 5 inhibitor CPD1 strongly alleviates CCl4-induced hepatic damage by inhibiting the activation of HSCs and expression of collagen fibers. © 2023 Publication Centre of Anhui Medical University. All rights reserved.     

5-Aminoimidazole-4-carboxamide-1-β-d-ribofuranoside alleviated carbon tetrachloride-induced acute hepatitis in mice

AMP-activated protein kinase (AMPK) is one of the principal cellular energy sensors participating in maintenance of energy balance but recent evidences also suggested that AMPK might be involved in the regulation of inflammation. In the present study, the AMPK activator 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) was used to investigate the potential roles of AMPK in carbon tetrachloride (CCl₄)-induced acute hepatitis. The experimental data indicated that treatment with AICAR significantly decreased the elevation of plasma aminotransferases and alleviated hepatic histological abnormalities in CCl₄-exposed mice. Treatment with AICAR also inhibited the increase of myeloperoxidase (MPO), the induction of TNF-α, IL-6, inducible nitric oxide synthase (iNOS), nitric oxide and the upregulation of matrix metalloproteinase 2 (MMP-2), MMP-3 and MMP-9 in mice exposed to CCl₄. These effects were associated with suppressed nuclear accumulation of NF-κB p65. These results indicated that the AMPK activator AICAR effectively suppressed the inflammatory responses and alleviated liver damage induced by CCl₄, implying that AMPK activation might be beneficial for ameliorating inflammation-based liver damage.     

High doses of bifendate elevate serum and hepatic triglyceride levels in rabbits and mice： animal models of acute hypertriglyceridemia

AIM: To investigate the effects of bifendate on serum and hepatic lipids level in rabbits and mice. METHODS: Animals were administered bifendate [powdered pill suspended in 0.5% sodium carboxymethylcellulose (CMC)] at increasing doses (0.25-1 g/kg, ig). Blood lipid and apolipoprotein levels were measured using commercially available assay kits. RESULTS: The treatment of rabbits with a single dose of bifendate (0.3 g/kg) caused a time-dependent and biphasic change in serum triglyceride (TG) levels, with the value reaching a maximum (3-fold increase compared to the baseline value) between 24 and 36 h post-dosing. When mice were orally treated with bifendate (0.25-1 g/kg), serum TG levels increased by 39%-76% and 14%-39% at 24 and 48 h post-dosing, respectively. When given at daily doses of 0.25 and 1 g/kg for 4 d, bifendate increased serum TG levels (56%-79%), with concomitant elevations in apolipoprotein A-I and apolipoprotein B levels at 24 h after the last dosing. TG levels were also increased (11%-43%) in liver samples of mice receiving single or multiple doses of bifendate. However, bifendate treatment caused slight reductions in serum and hepatic total cholesterol levels (9%-13%). The hypertriglyceridemia induced by bifendate was ameliorated by fenofibrate but not inositol nicotinate treatment in mice. CONCLUSION: The findings suggest that bifendate treatment at high oral doses can cause an acute elevation in serum and hepatic TG levels.     

Antidiabetic effect of a novel non-thiazolidinedione PPAR γ/α agonist on ob/ob mice

AIM: To study whether T33, a new synthesized non-thiazolidinedione (TZD) peroxisome proliferator-activated receptor (PPAR) gamma/alpha dual agonist has an antidiabetic effect on ob/ob mice. METHODS: Ob/ob mice were treated with 4 mg/kg or 8 mg/kg T33 by gavage for 20 d. Blood glucose levels were measured regularly. An oral glucose tolerance test (OGTT) and an insulin tolerance test (ITT) were preformed on d 8 and d 12, respectively. The levels of insulin, triglyceride and free fatty acid (FFA) in the serum were measured at the end of administration. The intramuscular and liver triglyceride content was also determined. RESULTS: T33 reduced the hyperglycemia, hyperinsulinemia and hyperlipidemia of the ob/ob mice. The OGTT and ITT showed that the insulin resistance state of the ob/ob mice was obviously ameliorated after T33 treatment. After 20 d treatment with 8 mg/kg T33, the triglyceride content in the gastrocnemius muscle decreased significantly. T33 did not have any effect on triglyceride content in the liver, whereas rosiglitazone significantly increased the hepatocyte lipid deposition. CONCLUSION: The PPARgamma/alpha dual agonist T33 has antidiabetic and insulin-sensitizing effects in ob/ob mice. It has the potential to be a new therapeutic candidate for the treatment of type 2 diabetes.     

Effects of Ganoderma sterols （GS） on hepatic cytochrome P450 in BCG-induced immunological hepatic injury in BALB／c mice

AIM: To investigate effects of Ganoderma sterols (GS) isolated from Ganoderma lucidum (Leyss ex fr) Karst on hepatic cytochrome P450 in BCG-induced immunological hepatic injury in BALB/c mice and its possible mechanism. METHODS: Immunological liver injury was induced by one intravenous injection of BCG (125 mg/kg) in BALB/c mice. One week later, successiveintragastric administration of GS (20, 40, 80 mg/kg, per day) and     

Distribution and accumulation of 10 nm silver nanoparticles in maternal tissues and visceral yolk sac of pregnant mice,and a potential effect on embryo growth

We examined the distribution of silver in pregnant mice and embryos/fetuses following intravenous injections of 10?nm silver nanoparticles (AgNPs) or soluble silver nitrate (AgNO₃) at dose levels of 0 (citrate buffer control) or 66?µg Ag/mouse to pregnant mice on gestation days (GDs) 7, 8 and 9. Selected maternal tissues and all embryos/fetuses from control, AgNP- and AgNO₃-treated groups on GD10 and control and AgNP-treated groups on GD16 were processed for the measurement of silver concentrations, intracellular AgNP localization, histopathology and gross examination of tissue morphology. Inductively-coupled plasma mass spectrometry revealed silver in all examined tissues following either AgNP or AgNO₃ treatment, with highest concentrations of silver in maternal liver, spleen and visceral yolk sac (VYS), and lowest concentrations in embryos/fetuses. For VYS, mean silver concentration following AgNO₃ treatment (4.87?ng Ag/mg tissue) was approximately two-fold that following AgNP treatment (2.31?ng Ag/mg tissue); for all other tissues examined, mean silver concentrations following either AgNP or AgNO₃ treatment were not significantly different from each other (e.g. 2.57 or 2.84?ng Ag/mg tissue in maternal liver and 1.61 or 2.50?ng Ag/mg tissue in maternal spleen following AgNP or AgNO₃ treatment, respectively). Hyperspectral imaging revealed AgNP aggregates in maternal liver, kidney, spleen and VYS from AgNP-treated mice, but not AgNO₃-treated mice. Additionally, one or more embryos collected on GD10 from eight of ten AgNP-treated mice appeared small for their age (i.e. Theiler stage 13 [GD8.5] or younger). In the control group (N?=?11), this effect was seen in embryos from only one mouse. In conclusion, intravenous injection of 10?nm AgNPs to pregnant mice resulted in notable silver accumulation in maternal liver, spleen and VYS, and may have affected embryonic growth. Silver accumulation in embryos/fetuses was negligible.     

Anti -inflammatory effect of Vam3 on asthmalike reaction induced by allergen in sensitized mice

An alcoholic extract of Vitis amurensis （ Vit A ） has been demonstrated to have strong anti - asthma action in two guinea pig models of acute asthma. Vam3 is the major component of Vit A and its anti - inflammatory action has been extensively investigated in our laboratory. Here, the effects of Vam3 on airway inflammation, cytokine production, and lung pathology were evaluated in a murine model of asthma. BALB/c mice were sensitized and challenged with ovalbumin （ OVA）, and developed airway inflammation and asthmalike syndrome. Oral administration of Vam3 significantly inhibited OVA- induced increases in total bronchoalveolar lavage （BALF） leukocyte numbers;     

The therapeutic effect of cimifugin on atopic dermatitis in mice and its mechanism北大核心CSCD

Aim To investigate the effects of cimifugin on mouse atopic dermatitis (AD) induced by fluorescein isothiocyanate (FITC) and further explore the mechanism of its action. Methods ICR mice were randomly divided into blank group, model group, positive group (dexamethasone),low dose group,high dose group and administration group of cimifugin. FITC solution was applied to the shaved abdomen of mice in the sensitization stage, and 0.6 % FITC solution was applied to attack the ears of mice in the stimulation stage. The administration groups were given medicine for seven consecutive days. The effects of cimifugin on body weight, thymus index and spleen index of mice were detected. Ear inflammatory cell infiltration was observed by HE staining. The ear swelling of mice was measured, and Th2 cytokines IL-5,IL-13 and the key promoter of allergy IL-33 were detected by ELISA. The epithelial barrier structural proteins, filaggrin, claudinl,occludin and E-cadherin,were detected by immunohistochemistry and Western blot. Results Compared with the blank group, the model group showed significant AD symptoms. Compared with the model group, cimifugin transdermal administration group significantly reduced ear inflammatory cell infiltration,ear swelling, IL-5,IL-13 and IL-33, and significantly increased the expression of filaggrin and occludin. Conclusions Transdermal administration of cimifugin could significantly inhibit AD in mice, and its mechanism involves repairing epithelial barrier function, restoring filaggrin and occludin, inhibiting allergy promoting factor IL-33, and finally inhibiting AD inflammation. © 2023 Publication Centre of Anhui Medical University. All rights reserved.     

Comparative effect of berberine and its derivative 8-cetylberberine on attenuating atherosclerosis in ApoE−/− mice

Berberine (BBR), one of the main bioactive compounds in Rhizoma coptidis, has multiple pharmacological activities. It has been reported that 8-cetylberberine (8-BBR-C16) has increased anti-microbial property in vivo and a higher bioavailability in hamsters. Therefore, in the present study, we used apolipoprotein E-deficient mice (ApoE^−/−) as an atherosclerosis model to investigate the anti-atherosclerosis effects of 8-BBR-C16. After 12 weeks of treatment, the atherosclerotic plaque area of the aorta, serum lipid profile, the plasma redox state and the expression of inflammatory cytokines in ApoE^−/− mice were determined. Both BBR and 8-BBR-C16 significantly decreased the atherosclerotic plaque area by suppressing inflammatory and oxidative markers in ApoE^−/− mice. Treatment with BBR or 8-BBR-C16, decreased serum levels of IL-1β and TNF-α as well as mRNA levels of NF-κBp65, i-NOS, ICAM-1, IL-6 in the aorta. In addition, the expression of NF-κB p65 protein decreased in the nucleus, whereas IκBα levels increased in the cytosol. The anti-inflammatory and anti-oxidative effect of BBR and 8-BBR-C16 attributed to inhibition of the translocation of NF-κB to the nucleus. Since the dosage of BBR used was 10 fold higher than that of 8-cetylberberine, we conclude that 8-BBR-C16 is more efficient in treating atherosclerosis in ApoE^−/− mice.