Downregulation in the human and mice cerebella after ketamine versus ketamine plus ethanol treatment

To study the deleterious effects of ketamine and the potential interaction effects between ethanol and ketamine on the cerebellum, functional magnetic resonance imaging (fMRI) tests were performed on the habitual ketamine users (n = 3) when they flexed and extended their upper limbs. Another fMRI test was performed on the same participants in which they consumed alcohol (12%, 200 mL) 1 h before the test. Downregulation on the activity of cerebellum was observed and the level of activation in the cerebellum decreased dramatically in habitual ketamine users with alcohol consumption before the test. Further studies were performed by using male ICR mice receiving treatment of ketamine only [30 mg kg(-1) intraperitoneally (i.p.)] or ethanol only everyday (0.5 mL 12% orally) and those with coadministration of the above dosages of ketamine and ethanol for 3 months. Fewer Purkinje cells were observed in the cerebellar sections of ketamine treated mice under silver staining. For TUNEL test, a significant increase in the apoptotic cells were observed in the cerebella of the ketamine treated mice (P = 0.016) and of those with co-administration of ketamine and ethanol (P < 0.001), when compared with the control. A statistical significance (P < 0.001) in two-way ANOVA test indicated that there might be an interactive mechanism between ethanol and ketamine acting on the cerebellum.     

Intestinal and liver changes after chronic ketamine and ketamine plus alcohol treatment

The effects of long‐term chronic ketamine treatment on the intestine and the liver were studied in the ICR mice which had daily intraperitoneal injection of ketamine at 30mg/kg per day for 7 months. The intestine showed no significant pathology after treatment but had a decrease of the positive sites of proliferative cell nuclear antigen in the mucosae of the intestines after ketamine and ketamine plus alcohol (added in the last month) treatment. No significant apoptosis (via TUNEL) nor necrosis (via lactic acid dehydrogenase) was detected in the intestines of all control and ketamine‐treated groups, with the exception of an increase of lactic acid dehydrogenase in the mucosae of the intestines of the ketamine plus alcohol group. In the liver, loss of glycogen was observed in animals after ketamine and ketamine plus alcohol treatment, in addition to the pathology reported in a previous work. The decrease in quantity of glycogen in the liver reflected either a failure of glycogen synthesis from glucose or an increase of glycogenolysis in the liver. Microsc. Res. Tech. 75:1170–1175, 2012. © 2012 Wiley Periodicals, Inc.     

柴胡皂苷D对小鼠乳腺癌治疗过程中的药物代谢影响研究

本工作建立了一种代谢组学方法用于研究柴胡皂苷D(SsD)对乳腺癌的治疗作用及其治疗过程中药物作用对机体代谢物产生的影响.采用不同浓度的SsD对小鼠乳腺癌肿瘤进行治疗,SsD给药不同天数后,采集小鼠血液,提取血清,进行超高效液相色谱-串联静电场轨道阱质谱(UPLC-Orbitrap MS)测定;筛查对照组、SsD低和高剂...     

液相色谱-电喷雾离子阱质谱法分析大鼠尿样中的黄芩苷及其异构体

采用液相色谱 -电喷雾离子阱串联质谱 ( LC/ MSn)技术分析了大鼠分别灌胃和静脉注射给予黄芩苷后尿样中原形药及其异构体的化学结构以及其排泄情况。根据代谢物的多级质谱和紫外吸收光谱数据推测 ,两种给药途径均检测到原形药黄芩苷及其异构体黄芩素 6-O-葡萄糖苷酸。收集大鼠灌胃 ( 1 0 0 mg/ kg)和静脉注射 ( 1 5 mg/ kg)给予黄芩苷后 0～ 48h尿样 ,以槲皮素作为内标 ,经乙酸乙酯提取后 ,以甲醇 -水 -甲酸 ( V(甲醇 )∶ V(水 )∶ V(甲酸 ) =60∶ 40∶ 1 )混合液为流动相 ,用 Diamonsil C18柱进行分离 ,采用电喷雾离子阱质谱 ,以选择反应监测 ( SRM)方式检测尿中黄芩素的两种葡萄糖醛酸结合物。黄芩素 6-O-葡萄糖苷酸的形成 ,说明黄芩苷在胃肠道可水解成苷元形式重新与葡萄糖醛酸结合 ,然后被排出体外。大鼠灌胃给予黄芩苷后 ,黄芩苷和黄芩素 6-O-葡萄糖苷酸的尿样累积排泄量分别为 1 .49%和 0 .77% ;大鼠静脉注射给予黄芩苷后黄芩苷和黄芩素 6-O-葡萄糖苷酸的尿样累积排泄量分别为 3 0 .80 %和 0 .2 8% ;以药物原形和尿药浓度评价黄芩苷在大鼠体内的绝对生物利用度为 4.84%。     

Astaxanthin delayed the pathogenesis of diabetic nephropathy in type 1 diabetic rats

This study was designed to investigate the protective effects of Astaxanthin (AST) in rats with diabetes mellitus (DM) induced by streptozotocin. SD rats were divided into control group (n = 5, only received normal saline), DM group (n = 8) and AST + DM group (n = 8; AST: 50 mg/kg/day). DM rats were induced by intraperitoneal injection of streptozocin (STZ, 65 mg/kg). Blood glucose level and body weight were determined at weeks 0, 2, 4, 6 and 8, respectively. At week 8, kidney function was determined, together with expression of P53 and dynamin-related protein-1 (Drp1) by Western blot analysis and immunofluorescence. AST led to increase of body weight in rats with DM. AST + DM group showed a significant decrease in blood glucose level at week 4 compared with DM group (P < 0.05). AST improved renal function and significantly reduced expression of P53 and Drp1 in DM rats. In addition, AST can effectively reduce the blood glucose in DM rats, and delayed the pathogenesis of diabetic nephropathy. Such delay mediated by AST may be associated with the downregulation of Drp1 and P53.     

Dose–response and histopathological study,with special attention to the hypophysis,of the differential effects of domoic acid on rats and mice

The effects of the neurotoxin domoic acid (DA) in the central nervous system of rodents (essentially rats and mice) after intraperitoneal administration have been profusely studied in the past. These observations have shown that the toxin induces similar symptoms and pathology in both species, but the lethality varies greatly. This article addresses the common and specific histopathological effects in rats and mice and the difference in sensitivity of these species to DA. Various sublethal and lethal doses were employed in mice (from 3 mg/kg to 8 mg/kg) to observe their neurotoxicity by using different histological techniques, and these results were compared with the pathological effects after the administration of LD50 in rats (2.5 mg/kg). Additionally we also detected the presence of this toxin in various tissues by means of immunohistochemistry. Our results showed that rats are more vulnerable than mice to the neurotoxic effects of DA after intraperitoneal inoculation: lethality was extremely high in rats and the toxin produced hippocampal damage in rats surviving the intoxication, while lesions were not observed in DA‐inoculated mice. As for similarities between rats and mice, both displayed similar clinical signs and in both the toxin was detected in the hypophysis by immunohistochemistry, a brain region not reported to date as target of the toxin. Microsc. Res. Tech. 78:396–403, 2015. © 2015 Wiley Periodicals, Inc.     

Effect of indirubin‐3‐monoxime against lung cancer as evaluated by histological and transmission electron microscopic studies

The aim of this study is to evaluate the antitumor effect of indirubin‐3‐monoxime and its mode of action in benzo(α)pyrene [B(α)P] induced lung cancer in A/J mice. Light microscopic examination of lung sections of [B(α)P] induced lung cancer mice revealed the presence of adenocarcinoma characterized by extensive proliferation of alveolar epithelium and loss of alveolar spaces. The control lung tissue showed a normal architecture with clear alveolar spaces. Interestingly the indirubin‐3‐monoxime treated groups showed the reduced adenocarcinoma with appearance of alveolar spaces. Transmission Electron Microscopic (TEM) studies of lung sections of [B(α)P] induced lung cancer mice showed the presence of phaemorphic cells with dense granules and increased mitochondria. The lung sections of mice treated with indirubin‐3‐monoxime showed the presence of shrunken, fragmented, and condensed nuclei implying apoptosis. The effects were dose dependent and prominent in 10 mg/kg/5 d/week groups suggesting the therapeutic role of indirubin analogue against this deadly human malignancy. Here, our results indicate that indirubin‐3‐monoxime brings antitumor effect against [B(α)P] induced lung cancer by its apoptotic action in A/J mice. Microsc. Res. Tech. 73:1053–1058, 2010. © 2010 Wiley‐Liss, Inc.     

Genotoxic and mutagenic effects of permethrin in mice: Micronuclei analysis in peripheral blood erythrocytes

Pyrethroids such as permethrin are synthetic compounds widely used in the agriculture of many countries to combat plagues and in domestic products, such as acaricides. Not so long ago these chemicals were characterized as non‐toxic for non‐target organisms; however, recent studies have showed that these compounds could present toxic potential for many organisms. In this sense, this study presents genotoxic and mutagenic potential of permethrin administered intraperitoneally in mice under artificial conditions by the use of micronucleus assay in the peripheral blood of these animals. The mice were divided into five groups: group I = negative control (distilled water), group II = positive control (cyclophosphamide), group III = 30% of permethrin LD₅₀ (96 mg/kg), group IV = 50% of permethrin LD₅₀ (160 mg/kg), and group V = 80% of permethrin LD₅₀ (256 mg/kg). The peripheral blood was collected 24, 48, and 72 h after treatment. Results showed that all the tested permethrin dosages presented genotoxic and mutagenic effects 24 h after treatment, which would contradict the classification of this chemical product as moderately toxic, i.e., unable to cause damages to the cell DNA. Microsc. Res. Tech. © 2012 Wiley Periodicals, Inc.     

地参多糖对正常及实验性糖尿病小鼠血糖的影响实验研究

目的：研究地参多糖对正常及实验性糖尿病小鼠血糖的影响。方法：。用地参多糖分别灌胃给予正常小鼠、四氧嘧啶（ALX）性糖尿病小鼠、肾上腺素（Adr）性及葡萄糖性高血糖小鼠模型,连续14d后,分别测定各组小鼠空腹血糖。结果：地参多糖对正常小鼠的血糖没有显著的降低作用,150mg/kg、300mg/kg地参多糖能显著降低四氧嘧啶性糖尿病小鼠高血糖,同时还能拮抗肾上腺素与外源性葡萄糖所致小鼠血糖升高,但150mg/kg地参多糖对肾上腺素性糖尿病小鼠高血糖无明显影响。结论：地参多糖能降低不同类型实验性糖尿病小鼠血糖。     

Expression and localization of translationally controlled tumor protein in rat urinary organs

This study describes the very first assessment of the expression and localization of translationally controlled tumor protein (TCTP) in adult rat urinary organs. TCTP expression levels in kidneys, urinary bladder, and urethra were evaluated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS–PAGE) and Western blotting, and its cellular localization was examined immunohistochemically in paraffin sections of various urinary organs. TCTP was found in all urinary organs. Its expression was high in the urethra and low in the bladder. TCTP was localized in glomerular podocytes, epithelium of proximal and distal renal tubules, in the loop of Henle, and in the transitional epithelium of the bladder and urethra, mostly in basal cell layers). The subcellular localization of TCTP in these urinary organs was cytoplasmic. These findings suggest that TCTP may be involved in urine formation and excretion. Microsc. Res. Tech. 2012. © 2012 Wiley Periodicals, Inc.     

Harmful effects of pyrethroid ester insecticide on the male reproductive system mainly through affecting testicular function and inflammatory markers

Pyrethroid esters are widely used as insecticides worldwide. In this study, we aimed to evaluate the harmful effect of deltamethrin on the male reproductive system through the assessment of reproductive hormones, inflammatory markers, and testicular function. To achieve our aim, eighty male 7-9-week-old, Wistar rats were taken, weighed, and divided into four experimental groups. The first group was kept as a control group, and the other three groups were given deltamethrin orally at different concentrations (0.87, 8.7, and 17.4 mg/kg body weight) for nine weeks. The results indicated that deltamethrin administration associated with a significant decrease in reproductive hormones, especially FSH, LH, and significant elevation in the interleukin 2 (IL2), interleukin 6 (IL6), histamine, and cortisol levels. Also, the significance of inhibition of sperm motility and viability, decreased testis weights, sperm count, and fructose in semen were noted. These findings clarify the harmful effect of deltamethrin on the male reproductive system by producing a significant alteration in reproductive hormones, inflammatory markers as well as testicular function.     

Piceatannol attenuates streptozotocin-induced type 1 diabetes in mice

As a natural analog of resveratrol, piceatannol (Pic) exhibits good antioxidant and anti-inflammatory activities in different disease models. However, the role of Pic in type 1 diabetes mouse model has not been reported yet. In this study, we investigated the in vivo effect of Pic in streptozotocin (STZ)-induced type 1 diabetic mice. Mice were injected with STZ to establish the type 1 diabetes mellitus (T1DM) model. After stable hyperglycemia was achieved, mice were then orally treated with Pic (40 mg/kg b.w., i.g.) for 30 days. The results indicated that Pic supplementation efficiently alleviated the typical symptoms associated with T1DM, including body weight loss, polydipsia, hyperglycemia, and hypoinsulinemia. Pic treatment also improved the glucose tolerance of STZ-induced diabetic mice. In addition, Pic supplementation markedly decreased the expression of pro-inflammatory molecules TNF-α and IL-6, the expression of endoplasmic reticulum (ER) stress markers GRP78 and CHOP, and the level of oxidative stress in T1DM mice. Moreover, Pic administration also partly reversed the metabolic profiles of STZ-treated mice as detected by ¹ H Nuclear Magnetic Resonance (NMR)-based metabolomics. Our study suggested that the therapeutic potential of Pic in type 1 diabetes and the anti-diabetic effects of Pic may be associated with its activities to suppress oxidative stress, inflammation, and ER stress.     

阿托伐他汀钙联合普罗布考治疗冠心病合并高脂血症疗效观察

目的观察分析联合阿托伐他汀钙与普罗布考治疗冠心病合并高脂血症的临床疗效。方法将符合标准的冠心病合并高脂血症患者76例随机分为对照组38例和实验组38例,对照组口服阿托伐他汀钙20 mg/d,1次/d;观察组在此基础上加服普罗布考500mg/d,2次/d。2组均连续服药8周。治疗前后对2组患者的TC、TG、LDC-L水平进行检测。结果治疗后2组间血脂指标TC、TG、LDC-L间差异具有统计学意义（P〈0.05）。观察组与对照组完成治疗后总有效率相比,差异具有统计学意义（P〈0.05）,2组均未见明显不良反应。结论联合阿托伐他汀钙与普罗布考联合治疗冠心病合并高脂血症临床效果优于单用阿托伐他汀钙,值得推广采用。     

Capsaicin exerts anti-benign prostatic hyperplasia effects via inhibiting androgen receptor signaling pathway

Background: Benign prostatic hyperplasia (BPH) is a common condition in middle-aged and elderly men. Enlargement of the prostate causes lower urinary tract symptoms. Capsaicin is a phytochemical extracted from chili peppers and exerts many pharmacological actions, such as anti-tumor and anti-inflammatory effects. Methods: Our study investigated the effect of capsaicin in vitro and in a mouse model in vivo. A prostatic stromal myofibroblast cell line (WPMY-1) was co-incubated with testosterone (1 µM) and different concentrations of capsaicin (10–100 µM) for 24 and 48 h. Capsaicin (10–100 µM) significantly inhibited testosterone-treated WPMY-1 cell growth at 48 h by MTT assay. The testosterone propionate (7.5 mg/kg)-induced BPH mouse model was used to examine the anti-proliferative effect of capsaicin. Treatment with capsaicin (10 mg/kg) for 14 days significantly attenuated prostatic hyperplasia. Finasteride was used as a positive control. Results: Capsaicin significantly decreased prostate weight and prostate index (prostate/body weight ratio) in BPH mice. The expression of 5α-reductase type II, androgen receptor (AR) and prostate specific antigen (PSA) protein expression and PSA serum were all significantly reduced in capsaicin-treated BPH mice. In addition, capsaicin also activated transient receptor potential vanilloid 1 mediated apoptosis and autophagy in BPH mice. Conclusion: These results demonstrate multiple positive effects of capsaicin in controlling prostate growth and suggest its therapeutic potential in the treatment of BPH.     

Protective effect of aqueous suspension of dried latex of Calotropis procera against oxidative stress and renal damage in diabetic rats

Calotropis species have been used in the traditional medicinal system for the treatment of diseases of the liver and abdomen. In view of the antioxidant and anti-hyperglycemic properties of an aqueous suspension obtained from the dried latex of Calotropis procera, the present study was carried out to evaluate its efficacy in affording protection against alloxan induced changes in rat kidney. A single intraperitoneal injection of alloxan (150 mg/kg) in rats produced hyperglycemia within 3 days and altered kidney functions over a period of 90 days. Daily oral administration of the aqueous suspension (100 and 400 mg/kg) in diabetic rats produced anti-hyperglycemic effect that was comparable to that of glibenclamide (10 mg/kg). Unlike glibenclamide, the aqueous suspension did not increase the serum insulin levels in diabetic rats. However, it produced a marked reduction in the levels of urinary glucose and protein and normalized the renal tissue levels of thiobarbituric acid-reactive substances (TBARS) and glutathione (GSH) in diabetic rats and the effect was comparable to that of glibenclamide. The protection afforded by the aqueous suspension was also evident from the histological analysis of the renal tissue. Our study shows that by exhibiting antioxidant and anti-hyperglycemic property the aqueous suspension of dried latex of C. procera affords protection against the complications associated with diabetes.     

Cytotoxicity of fipronil on mice liver cells

In the present study, mice livers were examined following exposure to different doses of fipronil (15, 25, and 50 mg/kg). Histological and histochemical techniques were used to determine the cytotoxic potential of this compound and to assess the damage it caused to livers. Mice were divided into four groups: control group and groups I, II, and III were exposed to 15, 25, and 50 mg/kg fipronil, respectively. Our findings revealed cytological, morphohistological, and histochemical alterations in liver cells of animals from groups I, II, and III compared to group control animals. These changes included Kupffer-cell proliferation, hepatocyte hypertrophy, accumulation and distribution of proteins, polysaccharides, lipids, and vacuoles in the cytoplasm of hepatocytes, and congestion of blood vessels. These phenotypes mainly characterize the following: (a) autophagic processes, (b) steatosis, and (c) cell death by necrosis, which demonstrate the damage caused by fipronil on nontarget organisms in artificial conditions.     

20(R)-ginsenoside Rg3, a product of high-efficiency thermal deglycosylation of ginsenoside Rd,exerts protective effects against scrotal heat-induced spermatogenic damage in mice

Heat stress (HS) reaction can lead to serious physiological dysfunction associated with cardiovascular and various organ diseases. Ginsenoside Rg3 (G-Rg3) is a representative component of ginseng rare saponin and can protect against multiple organs, also used as functional food to adjust the balance of the human body, but the therapeutic effect and molecular mechanism of G-Rg3 on male diseases under HS are underexplored. The aim of the present study, G-Rg3 was prepared through the efficient conversion of ginsenoside Rd and investigate the contribution of G-Rg3 to testicular injury induced exposure to HS. All mice were divided into four groups as follows: normal group, HS group, and HS+G-Rg3 (5 and 10 mg/kg) groups. G-Rg3 was administered orally for 14 days, then exposed to a single scrotal heat treatment (43°C, 18min) on the 7th day. After HS treatment, the morphology of testis and epididymis changes, and caused a significant loss of multinucleated giant cells, desquamation of germ cells in destructive seminiferous tubules, and degenerative Leydig cells, further destroying the production of sperm. After administration G-Rg3 (5 and 10 mg/kg/day) for 2 weeks, the spermatogenic-related indexes of testosterone levels and superoxide dismutase (SOD) activity, glutathione (GSH) content significantly (p < 0.01) increase compared with the HS group. Moreover, G-Rg3 treatment effectively ameliorated the production of malondialdehyde (MDA) (p < 0.05 or p < 0.01). Importantly, G-Rg3 exhibited the protective potential against HS-induced injury not only suppressing the protein levels of heme oxygenase-1 (HO-1), hypoxia-inducible factor-1α (HIF-1α), and heat shock protein 70 (HSP70) but also modulating the Bcl-2 family (p < 0.01 or p < 0.001) and activation of mitogen-activated protein kinase (MAPK) signaling pathways (p < 0.01). For most of the parameters tested, the HS+G-Rg3 (10 mg/kg) group exhibited potent effects compared with those exhibited by the low dose (5 mg/kg) group. In conclusion, the present study demonstrated that G-Rg3 exerted protective effects against HS-induced testicular dysfunction via inhibiting the MAPK-mediated oxidative stress and apoptosis in mice.     

石墨炉原子吸收光谱法测定土壤中的铅背景值

土壤样品用盐酸-硝酸-氢氟酸-高氯酸消解,并加入基体改进剂磷酸氢二铵,采用氘灯作背景校正,用石墨炉原子吸收光谱法测定土壤中铅的含量。加标回收率在98％～106％之间,RSD≤4．4％（n=6）。方法的检出为限为0．1mg／kg。应用该法对某区域土壤背景采样点不同土层中铅的背景值进行测定,结果表明,该区域土壤表层铅为25．1mg／kg,在纵向分布上无明显差异;与全国土壤表层铅的背景值26．0mg／ku相比,两者无明显差异。     

Protective effect of aqueous suspension of dried latex of <i>Calotropis procera</i> against oxidative stress and renal damage in diabetic rats

Calotropis species have been used in the traditional medicinal system for the treatment of diseases of the liver and abdomen. In view of the antioxidant and anti-hyperglycemic properties of an aqueous suspension obtained from the dried latex of Calotropis procera, the present study was carried out to evaluate its efficacy in affording protection against alloxan induced changes in rat kidney. A single intraperitoneal injection of alloxan (150 mg/kg) in rats produced hyperglycemia within 3 days and altered kidney functions over a period of 90 days. Daily oral administration of the aqueous suspension (100 and 400 mg/kg) in diabetic rats produced anti-hyperglycemic effect that was comparable to that of glibenclamide (10 mg/kg). Unlike glibenclamide, the aqueous suspension did not increase the serum insulin levels in diabetic rats. However, it produced a marked reduction in the levels of urinary glucose and protein and normalized the renal tissue levels of thiobarbituric acid-reactive substances (TBARS) and glutathione (GSH) in diabetic rats and the effect was comparable to that of glibenclamide. The protection afforded by the aqueous suspension was also evident from the histological analysis of the renal tissue. Our study shows that by exhibiting antioxidant and anti-hyperglycemic property the aqueous suspension of dried latex of C. procera affords protection against the complications associated with diabetes.     

Aged garlic extract ameliorates the oxidative stress,histomorphological, and ultrastructural changes of cisplatin‐induced nephrotoxicity in adult male rats

Aim: Aged garlic extract (AGE) is a natural dietary substance having different antioxidant free‐radical‐scavenger compounds that ameliorates the toxicity of the oxidative stress. This study aimed to investigate the effect of AGE on cisplatin (CP)‐induced nephrotoxicity in rats. Materials and Methods: Twenty‐four, adult male Wistar albino rats were randomly divided into four groups namely control, AGE‐treated (a single oral dose of 250 mg/kg/day for 21 days), CP‐treated (a single intraperitoneal dose of 7.5 mg/kg on Day 16), and AGE + CP‐treated (AGE at a dose of 250 mg/kg/once daily for 21 days and a single dose of CP of 7.5 mg/kg intraperitoneally on Day 16). Body weight and absolute and relative kidney weights of each rat were calculated. Serum creatinine, uric acid, and urea levels were determined. Level of malondialdehyde and reduced glutathione and activity of superoxide dismutase and catalase of renal tissues were measured. Renal specimens from each rat were prepared for both light and electron microscopic examinations. Results: Interstitial cell infiltration, hemorrhage, glomerular atrophy, necrosis, and tubular degeneration were observed after CP treatment. Superoxide dismutase and catalase activities and glutathione level were significantly decreased and malondialdehyde level was significantly increased in CP‐treated rats compared with AGE + CP‐treated animals. A remarkable improvement in the histopathological and ultrastructural changes induced by CP in renal tissues was observed in AGE + CP‐treated rats. Conclusion: AGE exhibited antioxidant effect that could ameliorate the nephrotoxic effects of CP. Microsc. Res. Tech. 78:452–461, 2015. © 2015 Wiley Periodicals, Inc.