Effect of Caralluma tuberculata on the cytological and biochemical changes induced by cyclophosphamide in mice.

Treatment with Caralluma tuberculata extract induced complex biochemical and cytological changes in mice. Its cytotoxicity in the bone marrow cells of mice was comparable with that of the standard drug cyclophosphamide (CP); however, unlike CP, C. tuberculata was not clastogenic (as shown by the micronucleus assay). A dose-dependent decrease in the RNA content of liver and testes was produced by C. tuberculata treatment whereas there was no effect on the content of nucleic acid and protein in the brain. In the extract-treated animals there was a significant and dose-dependent increase in the DNA content of the liver, with a negligible effect on the protein content. Combined treatment with C. tuberculata and CP showed that C. tuberculata diminished the effect of CP on DNA levels; however, RNA levels were further suppressed, resulting in increased cytotoxicity. Pretreatment with C. tuberculata extract significantly reduced the clastogenicity of CP. These results indicated the involvement of different phytoconstituents acting by different routes.     

Protective effects of betulinic acid on intestinal mucosal injury induced by cyclophosphamide in mice

BackgroundBetulinic acid (BA) is a plant-derived pentacyclic triterpenoid with a variety of biological activities. The purpose of this study was to assess the potential protective role of BA against intestinal mucosal injury induced by cyclophosphamide (CYP) treatment.MethodsMice were pretreated with BA daily (0.05, 0.5, and 5.0 mg/kg) for 14 days, then injected intraperitoneally with CYP (50 mg/kg) for 2 days.ResultsBA pretreatment reduced the contents of malondialdehyde (MDA) and glutathione (GSH), decreased the activity of superoxide dismutase (SOD) in small intestine, increased villus hight/crypt depth ratio and restored the morphology of intestinal villi in CYP-induced mice. Moreover, BA pretreatment could significantly down-regulate the levels of pro-inflammatory cytokines interleukin-5 (IL-5), IL-17, IL-12 (P70) and tumor necrosis factor α (TNF-α), reduced production of chemokines macrophage inflammatory protein-1α (MIP-1α), macrophage inflammatory protein-1β (MIP-1β) and regulated upon activation, normal T-cell expressed and secreted (RANTES), and enhanced the levels of anti-inflammatory such as IL-2 and IL-10 in serum, and decreased the mRNA expressions of IL-1β and TNF-α in intestine of CYP-induced mice. Furthermore, RT-PCR demonstrated that BA improved intestinal physical and immunological barrier in CYP-stimulated mice by enhancing the mRNA expressions of zonula occluden 1 (ZO-1) and Claudin-1.ConclusionsBA might be considered as an effective agent in the amelioration of the intestinal mucosal resulting from CYP treatment.     

Modulatory effects of gentisic acid against genotoxicity and hepatotoxicity induced by cyclophosphamide in Swiss albino mice

Objectives This study evaluated the protective effects of gentisic acid (GA) against genotoxicity and hepatotoxicity induced by cyclophosphamide (CP) in Swiss albino mice. Methods Mice were pretreated with GA orally at doses of 50 and 100 mg/kg for 14 consecutive days before the administration of a single intraperitoneal dose of 50 mg/kg CP. The ameliorative effect of GA on genotoxicity was studied using the in‐vivo bone marrow micronuclei induction test, DNA integrity and alkaline unwinding assay. The activity of various oxidative stress enzymes were estimated in hepatic tissue. Key findings A single intraperitoneal administration of CP in mice increased the malondialdehyde level, depleted the glutathione content and antioxidant enzyme activity (glutathione peroxidase, glutathione reductase, catalase and quinone reductase), and induced DNA strand breaks and micronuclei induction. Oral pretreatment with GA at both doses caused a significant reduction in malondialdehyde and glutathione levels, restoration of antioxidant enzyme activity, reduction in micronuclei formation and DNA fragmentation. Serum toxicity marker enzymes such as aspartate aminotransferase, alanine aminotransferase and lactate dehydrogenase were increased after CP treatment but restored in GA pretreated groups. Conclusion The results support the protective effect of GA against CP induced genotoxicity and hepatotoxicity.     

Emesis-related biochemical and histopathological changes induced by cisplatin in the ferret.

Cisplatin is an effective antineoplastic agent that causes severe vomiting due to unknown mechanism. The ferret, an animal model useful in the determination of emetic activity, was used to clarify the emesis-related biochemical and histopathological changes that were induced by cisplatin. Cisplatin (5 to 10 mg/kg) was administered intraperitoneally and a 7-10 mg/kg i.p. dose evoked dose-dependent emesis in the ferret. Almost all cisplatin-vomiting episodes occurred within a 6 hour observation period. All ferrets receiving cisplatin in this study died within 3-5 days. Significant increases in ileal mucosal levels of serotonin and norepinephrine were observed in cisplatin-treated ferrets. There were no significant changes in the levels of serotonin and dopamine in the gastric mucosa. Also, karyorrhexis was observed in the epithelial cells of the ileum and in the lymph follicles of the spleen of cisplatin-treated ferrets. These significant biochemical and pathological changes in the ileum may play an important role in cisplatin-induced emesis.     

白族药西归对环磷酰胺所致小鼠免疫功能低下的影响

目的：观察白族药西归乙醇提取物对环磷酰胺所致小鼠免疫功能低下的影响。方法：取60只小鼠随机分为6组,分别为空白对照组（生理盐水）、模型组（生理盐水）、阳性对照组（人参浸膏2.0 g·kg^-1·d^-1）、西归乙醇提取物高、中、低剂量组（西归浸膏13.4,6.6,3.3 g·kg^-1·d^-1）。每次给药前,除空白对照组外,其余各组均腹腔注射环磷酰胺（20 mg·kg^-1·d^-1,每2天腹腔注射1次）,建立小鼠免疫低下模型。各组于腹腔注射环磷酰胺1 h后,再灌胃相应的药物,连续给药14 d。治疗后,分别测定各组小鼠脏器质量、脏器指数;血清中免疫球蛋白G（IgG）、免疫球蛋白M（IgM）的含量;小鼠血清中丙二醛（MDA）含量、超氧化物歧化酶（SOD）活性;血常规。结果：西归乙醇提取物能明显提高免疫力低下小鼠脏器质量和脏器指数;明显提高免疫低下小鼠血清IgG、IgM含量;明显降低血清中MDA含量及提高血清中SOD活性;明显改善小鼠外周血血细胞及血红蛋白含量（P<0.05或P<0.01）。结论：西归乙醇提取物能改善免疫力低下小鼠的免疫功能及造血功能。     

Ginger extract ameliorates paraben induced biochemical changes in liver and kidney of mice

The present investigation was undertaken to evaluate the effect of paraben (p-hydroxybenzoic acid) on acidic, basic, and neutral proteins content, as well as carbohydrate and cholesterol contents in liver and kidney of mice. Adult female albino mice were orally administrated with 2.25 and 4.5 mg of paraben in 0.2 mL of olive/animal/day for thirty days. The results revealed dose dependent, significant reduction in acidic, basic, and neutral protein, carbohydrate contents and an increase in cholesterol content of the investigated liver and kidney. Oral administration of aqueous extract of Zinziber officinale (3 mg/animal/day) along with paraben for thirty days caused significant amelioration in all the protein types, carbohydrate and cholesterol of liver and kidney.     

氧化苦参碱协同增加环磷酰胺诱导小鼠肝毒性的研究

环磷酰胺(cyclophosphamide,CPA)是治疗多种肿瘤的一线化疗药,但过量应用可引起肝损伤。本文旨在探讨氧化苦参碱(oxymatrine,OMT)与CPA的联合给药是否会加剧其肝毒性,并初步阐明其机制。小鼠单独给药OMT(100 mg·kg^-1)不同时间后,检测肝组织Cyp2b10 mRNA和CYP2B10蛋白表达。小鼠灌胃(intragastric adminis‐tration,ig)给药不同剂量OMT,同时隔天腹腔注射(intraperitoneal injection,ip)给予CPA(200 mg·kg^-1),10天后,检测血清谷丙/谷草转氨酶(alanine/aspartate aminotransferase,ALT/AST)活力,记录小鼠死亡率,检测肝组织Cyp2b10mRNA水平,并分析ALT/AST活力、死亡率和Cyp2b10 mRNA水平间的相关性。本文中动物福利和实验过程均遵循上海中医药大学实验动物伦理委员会的规定。结果发现,OMT单独给药可以显著提高小鼠肝组织中Cyp2b10mRNA和CYP2B10蛋白表...     

Antimutagenic activity of ipriflavone against the DNA-damage induced by cyclophosphamide in mice

In the present study we evaluated the potential of ipriflavone against the cytotoxic and mutagenic effects induced by cyclophosphamide chemotherapeutic agent in bone marrow cells of mice, using the micronucleus assay in vivo on cells of bone marrow. The study was performed following three protocols: pre-treatment, simultaneous treatment and post treatment. The results demonstrated that ipriflavone has a protective effect against mutagenicity induced by cyclophosphamide in the pre-treatment and post-treatment and against the cytotoxicity in all treatments. There was variation between the genders in some of the experimental groups. To evaluate their possible mechanisms of action, it was performed the DPPH assay, which showed no ability to donate hydrogens, suggesting that it acts through other mechanisms. Due to its ability to prevent chromosomal damage, ipriflavone is likely to open an interest field concerning its possible the use in clinical applications.     

拆分硫普罗宁对放射线和环磷酰胺所致白细胞减少的防治作用

目的研究硫普罗宁(MPG)拆分体对放射线、环磷酰胺(CTX)引起的白细胞减少的防治作用。方法通过60Co-γ射线照射和注射CTX建立小鼠放射线、CTX致白细胞减少模型。尾静脉注射MPG及其拆分体,于不同时间点采血,以白细胞计数观察各药对外周血白细胞减少的作用。结果消旋和左旋MPG高、中、低剂量组对放射线及CTX致白细胞减少具有显著防治作用(与模型组比较:P<0.01～0.05);右旋MPG高剂量组对放射线及CTX致白细胞减少具有显著的治疗作用(与模型组比较:P<0.01～0.05)。左旋MPG中剂量组对放射线及CTX致白细胞减少预防作用,左旋MPG低剂量组对放射线照射、左旋MPG高、中、低剂量组对CTX致白细胞减少的治疗作用强(与同剂量消旋MPG组比较:P<0.01～0.05)。结论消旋和左旋MPG高、中、低剂量组对放射线及CTX致白细胞减少有防治作用。     

Morphological and biochemical changes associated with apoptosis induced by okadaic acid in human amniotic FL cells

The marine toxin okadaic acid (OA) is an apoptosis inducer and a tumor promoter. During recent years, extensive studies have demonstrated that OA can induce apoptosis in a wide variety of cell types. In contrast to the relatively longer incubation time or higher treatment concentrations of OA in apoptosis shown previously, relatively lower concentrations (相似文献   

Chicoric acid regulates behavioral and biochemical alterations induced by chronic stress in experimental Swiss albino mice

The present study was taken up to see the effect of chicoric acid (CA) on behavioral and biochemical alterations induced by chronic restraint stress in experimental Swiss albino mice. CA at 1 mg/kg dose level exhibited considerable antidepressant activity as shown by significant decrease in immobility period in the Porsolt's swim stress-induced behavioral despair test and escape failures in Learned “helplessness test”. The antidepressant activity shown by CA can be attributed to its modulating effect on nor-adrenaline (NA), dopamine (DA) and 5- hydroxy tryptamine (5-HT) as shown by their quantification in CA treated chronically stressed mice. Further, a significant antioxidant effect was exhibited by CA as shown by estimation of lipid peroxidation, glutathione (GSH) and glycogen in liver of chronically stressed mice. It also normalized altered values of serum glucose, triglycerides, aspartate aminotransferase (AST) alanine aminotransferase (ALT) and alkaline phosphatase (ALP) in a dose dependent manner. The stress busting potential of CA was further confirmed by its regulating effect on raised plasma corticosterone levels and significant attenuation of the depleted ascorbic acid, cholesterol and corticosterone levels in adrenal glands. Thus, our results suggest that CA possesses considerable stress busting potential, and that anti-oxidation may be one of the mechanisms underlying its antistress action.     

The protective effect of hydrated sodium calcium aluminosilicate against haematological, biochemical and pathological changes induced by Zearalenone in mice.

Hydrated sodium calcium aluminosilicate (HSCAS), an anticaking agent for mixed feed, was added alone or simultaneously with a toxic Zearalenone (ZEN) dose to balb/c mice and was evaluated for its ability to restore damages induced by ZEN. The latter is a mycotoxin produced by fusarium genera; it is mainly known to induce several toxic effects such as hepatotoxicity, immunotoxicity and nephrotoxicity on animals and humans. The experimental approach consisted of eight treatments of six mice each by 400 mg/kg bw or 5 g/kg bw of HSCAS. Two experimental groups have received respectively ZEN alone at 40 (8% of LD50) and at 500 mg/kg bw (LD50). Two other groups have received ZEN at 40 or 500 mg/kg bw combined respectively with HSCAS at 400 mg/kg bw and 5 g/kg bw. The control groups received water or olive oil. Forty-eight hours after treatment, blood samples were collected for haematological and serum biochemical parameters measurements. ZEN treatment significantly increased hematocrit, haemoglobin, white blood cells: lymphocytes, eosinophils, neutrophils, monocytes and the most of biochemical serum parameters; it significantly reduced platelets and induced degenerative changes in the hepatic and renal tissues; while, the mixture of HSCAS with ZEN induced a reestablishment of haematological parameters, levels of serum biochemical enzyme activities and histological pictures of both liver and kidney. It also prevented general toxicity of ZEN. This was observed by the shift of LD50 for this toxin. Thus, our data strongly suggested that deleterious effects of ZEN could be overcome or, at least, significantly were diminished by HSCAS. Moreover, this sorbent by itself did not show any toxic effects.     

Cardioprotective effect of lemon grass as evidenced by biochemical and histopathological changes in experimentally induced cardiotoxicity

Isoproterenol is a synthetic catecholamine found to cause toxicity leading to severe stress in the myocardium of experimental animals. The aim of the present study is to evaluate the cardioprotective effect of Cymbopogon citratus, which is used as a culinary item and commonly known as lemon grass (LG), in isoproterenol-induced cardiotoxicity. Male Wistar albino rats were segregated into five different groups as follows. Groups I and II rats were treated with vehicle. Groups III and IV rats were treated with 100 and 200 mg/kg b.wt. of LG. Group V with 100 mg/kg b.wt. of vitamin E. Myocardial necrosis was induced in Groups II, III, IV and V on 58(th) and 59(th) day using isoproterenol at a dose of 85 mg/kg twice at 24-hour interval. Animals were sacrificed on the 60( th) day. LG pretreatment exhibited cardioprotective activity as evidenced by decreased activity of cardiac markers in serum and increased the same in heart homogenate (p < 0.05). LG administration decreased the toxic events of lipid peroxidation (TBARS) in both serum and heart tissue, by increasing the level of enzymatic antioxidants and non-enzymatic antioxidants significantly in both heart homogenate and serum sample (p < 0.05). The histopathological observations also revealed that the cardioprotective effect of LG extract was observed at a dose of 200 mg/kg b.wt. The results of the present study reveal that LG is cardioprotective and antilipid peroxidative by increasing various antioxidants at a dose of 200 mg/kg b.wt., which is comparable with that of vitamin E.     

Citrus extract modulates genotoxicity induced by cyclophosphamide in mice bone marrow cells

The protective effect of citrus extract was investigated by using the micronucleus assay for anticlastogenic activity in mouse bone marrow cells; liver glutathione (GSH) content was determined against toxicity induced by cyclophosphamide. Mice were orally (gavage) pretreated with solutions of citrus peel extract (Citrus aurantium var. amara) prepared at three different doses (100, 200 and 400 mg kg(-1;) body weight) for 7 consecutive days. Then mice were injected intraperitoneally on the seventh day with cyclophosphamide (50 mg kg(-1)) and after 24 h killed for the evaluation of micronucleated polychromatic erythrocytes (MnPCEs) in bone marrow cells. Non-protein thiol levels in liver were estimated in mice injected with citrus extract with or without cyclophosphamide treatment. Administration of citrus extract before cyclophosphamide treatment significantly reduced the frequency of MnPCEs in mice bone marrow compared with the group treated with cyclophosphamide alone (P<0.0001-0.05). Citrus extract at a dose of 400 mg kg(-1) reduced MnPCEs 2.8 fold against genotoxicity induced by cyclophosphamide. Administration of cyclophosphamide depleted the GSH level in liver. Citrus extract showed excellent scavenging effects on 1,1-diphenyl-2-picryl hydrazyl radical (DPPH) at a concentration of 1.6 mg mL(-1). Application of citrus extract 1 h before cyclophosphamide treatment allowed GSH content to reach the normal level. It appeared that citrus extract, particularly flavonoids constituents with antioxidative activity, may return the GSH level to normal in stress conditions and reduces genotoxicity induced by cyclophosphamide in bone marrow cells.     

Heterogeneity of splenic natural suppressor cells induced in mice by treatment with cyclophosphamide

Administration of high dose cyclophosphamide (CY, 200 mg/kg body weight) to adult mice induces transient, nonspecific suppressor activity in the spleen of treated animals. Characterization of the CY-induced natural suppressor (NS) cells which inhibit mixed lymphocyte reactions revealed a heterogenous population of lymphocytes expressing the CD8 T cell marker and the B220 B cell marker, as well as cells bearing the granulocyte-monocyte marker CD11b. On a cell per cell basis the most potent of these suppressors were found to be positive for CD11b. Inhibitory activity was also detected in the CD8⁻, CD11b⁻, B220⁻ compartment of CY-spleen, suggesting the presence of null NS cells. The fact that several phenotypically distinct cell populations contribute to the overall inhibitory effect of CY-spleen cells indicates that natural suppression defines an activity rather than a specific cell type. Interestingly, NS activity was observed to reside solely within the fraction of CY-spleen that is agglutinable with soybean agglutinin or wheat germ agglutinin, suggesting that expression of receptors for these plant lectins is a universal characteristic of CY-induced NS cells, regardless of their lineage. CY-spleen cell-mediated suppression of lymphoproliferative responses was found to be partially dependent on DNA synthesis and totally dependent on protein synthesis, but did not require cell-cell contact, indicating the production of soluble suppressor factor(s).     

Quantitative prediction of catalepsy induced by amoxapine, cinnarizine and cyclophosphamide in mice

Parkinsonism can be a side effect of antipsychotic drugs, and has recently been reported with peripherally acting drugs such as calcium channel blockers, antiarrhythmic agents and so on. In this study, we examined the quantitative prediction of drug-induced catalepsy by amoxapine, cinnarizine and cyclophosphamide, which have been reported to induce parkinsonism. Dose-dependent catalepsy was induced by these drugs in mice. In vivo dopamine D(1), D(2) and muscarinic acetylcholine (mACh) receptor occupancies by these drugs in the striatum were also examined. The in vitro binding affinities (K(i) values) of amoxapine and cinnarizine to dopamine D(1), D(2) and mACh receptors in rat striatal synaptic membrane were 200 and 2900 nM, 58.4 and 76.4 nM and 379 and 290 nM, respectively. Cyclophosphamide did not bind to these receptors at concentrations up to 100 microM. Twenty drugs, including those mentioned above, showed a significant correlation between the observed intensity of catalepsy and the values predicted with a pharmacodynamic model (Haraguchi K, Ito K, Kotaki H, Sawada Y, Iga T. Prediction of drug-induced catalepsy based on dopamine D(1), D(2), and muscarinic acetylcholine receptor occupancies. Drug Metab Disp 1997; 25: 675-684) based on in vivo occupancy of dopamine D(1), D(2) and mACh receptors. We conclude that occupancy of dopamine D(1) and D(2) receptors contributes to catalepsy induction by amoxapine and cinnarizine.     

海牡方对环磷酰胺所致小鼠造血功能损伤的保护作用

目的 研究中药复方制剂海牡方对小鼠造血功能损伤的保护作用。方法 单次尾静脉给予大剂量(250 mg/kg)的环磷酰胺建立小鼠白细胞减少症模型;灌胃给予不同剂量的海牡方受试物,观察对小鼠血细胞、骨髓细胞DNA含量等的影响。结果 海牡方可以促进模型小鼠的白细胞、红细胞及血小板计数水平的恢复(p<0.01),缓解骨髓细胞DNA含量的降低。结论 海牡方能促进环磷酰胺模型小鼠造血机能的恢复,对环磷酰胺所致骨髓损伤具有一定的保护作用。