Effect of selenium-enriched malt on VEGF and several relevant angiogenic cytokines in diethylnitrosamine-induced hepatocarcinoma rats

One hundred and ninety-three Sprague–Dawley (SD) rats (average body weight 100–120 g) were randomly divided into five groups (I–V). Groups I and II rats served as the negative and positive controls respectively and both received 0.1 mg/kg Se from sodium selenite supplemented diets for the 18-week experimental period. Groups III–V rats were fed Se from SEM supplemented diets (0.3, 1 and 3 mg/kg respectively). To induce hepatocarcinoma, groups II–V rats received diethylnitrosamine solution (100 mg/L) at the dosage of 10 mg/kg body weight in drinking water daily for 16 weeks, followed by sterilized water for a further 2 weeks. Group I rats received sterilized water throughout. At weeks 4, 8, 12 and 16 five rats in each group were sacrificed by cervical decapitation. At the termination of the study, at week 18, the surplus rats were sacrificed by cervical decapitation. Feed was withheld from the rats for 12  h before sampling. The following items including TNF-α, IGF-II, NO and T-NOS levels in plasma were tested using kit techniques. At the same time the expression of vascular endothelial growth factor (VEGF) in tumor tissue was analyzed by immunohistochemistry using the envision two-step methods with a kit. The results indicated that SEM could increase the levels of TNF-α in the early stages of hepatocarcinoma formation, however there was a decrease in the later stage of hepatocarcinogenesis. SEM could also significantly decrease the levels of IGF-II and NO, and inhibit the expression of VEGF in tumor tissue. SEM delayed the development of hepatocarcinoma in rats and that could be partially attributed to inhibition of angiogenesis.     

The hypoglycemic activity of Euclea undulata Thunb. var. myrtina (Ebenaceae) root bark evaluated in a streptozotocin–nicotinamide induced type 2 diabetes rat model

The hypoglycemic activity of a crude acetone extract of the root bark of Euclea undulata var. myrtina was evaluated in a streptozotocin–nicotinamide induced type 2 diabetes rat model after positive results were obtained by in vitro screening of glucose utilization by C2C12 myocytes, 3T3-L1 preadipocytes and Chang liver cells and alpha-glucosidase inhibition. Thirty male Wistar rats were used for the experiment. Type 2 diabetes was induced by a single intraperitoneal injection of streptozotocin and administration of nicotinamide 15 min after. Animals exhibiting fasting glucose levels of 140–200 mg/dl after 7 days were screened as type 2 diabetes. Extract was administered for 21 days orally at a concentration of 50 mg/kg and 100 mg/kg respectively. Glibenclamide (1 mg/kg) was used as positive control. On day 21, blood lipid profiles and body weight were determined by using standard enzymatic colorimetric kits before the rats were sacrificed by cervical decapitation. The crude acetone extract of E. undulata root bark at a concentration of 100 mg/kg body weight significantly lowered fasting blood glucose levels as well as elevated cholesterol and triglyceride levels to near normal without any weight gain. The results indicate that the crude acetone root bark extract of E. undulata exhibit antidiabetic activity in type 2 induced diabetic rats. It confirms the in vitro screening results as well as its use in the treatment of diabetes by traditional healers and herbalists in southern Africa.     

Antiosteoporotic activity of icariin in ovariectomized rats

Icariin was evaluated for its antiosteoporotic activity in an ovariectomized rat model of osteoporosis. The rats were divided into sham and OVX groups. The OVX rats were then subdivided into five groups treated with water, nylestriol (1 mg/kg body weight, weekly, orally) or icariin (ICA) (5, 25, and 125 mg/kg body weight, daily, orally) for 12 weeks. In OVX rats, the increases of body weight, serum BGP and ALP were significantly decreased by ICA treatment. In OVX rats, atrophy of uterus and descent of BMD were suppressed by treatment with ICA. In addition, ICA (125 mg/kg body weight) completely corrected the decreased serum concentration of Calcium, Phosphorus, and E₂ observed in OVX rats. ICA (125 mg/kg body weight) increased biomechanical strength significantly in comparison to the sham group. Histological results also showed its protective action through promotion of bone formation. The findings, assessed on the basis of biochemical, bone mineral density, biomechanical, and histopathological parameters, showed that ICA has a definite antiosteoporotic effect, similar to estrogen, especially effective for prevention bone fracture induced by estrogen deficiency.     

Pretreatment with a combination of quercetin and α-tocopherol ameliorates adenosine triphosphatases and lysosomal enzymes in myocardial infarcted rats

AimsMembrane bound adenosine triphosphatases (ATPases) and lysosomal enzymes play an important role in the pathology of myocardial infarction. This study was aimed to evaluate the combined preventive effects of quercetin and α-tocopherol on membrane bound ATPases and lysosomal enzymes in isoproterenol induced myocardial infarcted rats.Main methodsMale Wistar rats were pretreated with a combination of quercetin (10 mg/kg) and α-tocopherol (10 mg/kg) daily for 14 days. After the pretreatment period, isoproterenol (100 mg/kg) was injected to rats at an interval of 24 h for two days to induce myocardial infarction. The activities of ATPases and lysosomal enzymes were assayed.Key findingsIsoproterenol treated rats showed decreased levels of heart creatine kinase and lactate dehydrogenase. The activity of sodium potassium adenosine triphosphatase was decreased and the activities of magnesium adenosine triphosphatase and calcium adenosine triphosphatase were increased in isoproterenol treated rats. Also, the activities of β-glucuronidase, β-N-acetylglucosaminidase, β-galactosidase, cathepsin-B and D were increased (serum and heart), but the activities of β-glucuronidase and cathepsin-D were decreased in lysosomal fraction and increased in cytosolic fraction of the heart in isoproterenol treated rats. Furthermore, the heart lipid peroxidation products were increased in isoproterenol treated rats. Combined pretreatment with quercetin and α-tocopherol to isoproterenol treated rats normalized all the biochemical parameters studied. The observed effects are due to their membrane stabilizing property and this property might be due to decreased lipid peroxidation.SignificanceOur study demonstrated that combined pretreatment was better than single pretreatment. This study may have significant impact on myocardial infarcted patients.     

Celery oil modulates DEHP-induced reproductive toxicity in male rats

The objective of the study was to investigate the protective effect of Apium graveolens (AP) against di-(2-ethylhexyl) phthalate (DEHP)-induced testes injury in rats. Adult rats were divided into nine groups: (1) control group (no treatment); (2) corn oil (60 μg/kg body weight – bwt); (3) AP (50 μg/kg bwt); (4) 300 mg DEHP/kg bwt; (5) 500 mg DEHP/kg bwt; (6) 1000 mg DEHP/kg bwt; (7) 300 mg DEHP/kg bwt + AP; (8) 500 mg DEHP/kg bwt + AP; and (9) 1000 mg DEHP/kg bwt + AP. Oral administration of treatments was performed daily for 6 weeks. DEHP decreased (p < 0.01) body weight, testis weight and serum concentrations of testosterone, cholesterol and total proteins. Moreover, DEHP increased (p < 0.001) total antioxidant capacity in the testis and plasma DEHP level. In addition, DEHP decreased mRNA expression of two testicular steroidogenic enzymes: 3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase. DEHP also caused atrophy, vacuolar degeneration and aspermia of the seminiferous tubules. AP administered concurrently with DEHP effectively alleviated most of the DEHP-induced effects. In conclusion, in male rats, DEHP had adverse effects on the testis including inhibition of androgen production. A concurrent administration of A. graveolens (celery oil) protected the testis against DEHP-induced toxicity.     

Metabolic effect of short term administration of Hoodia gordonii,an herbal appetite suppressant

Hoodia gordonii (family: Apocynaceae) is used traditionally by the Khoi-San tribes to control hunger. It has become extremely popular and has triggered commercial interest due to its appetite suppressant property. The present study was undertaken to investigate the appetite regulatory mechanism and associated metabolic changes induced by the herb. Effect of organic solvent extract of H. gordonii on food intake and body weight of male Sprague Dawley rats was monitored at three different doses 50, 100 and 150 mg/kg body weight, given orally for five days. Subsequently, the dose of 100 mg/kg body weight was selected for further studies on the regulatory hormones and biochemical variables. Dose-dependent reduction in food intake (12–26%) was observed at a dose of 100 and 150 mg/kg body weight (p < 0.05). Appetite suppression persisted for 6 h and food intake was restored within 24 h after stopping of the treatment. There was an increase in liver glycogen stores, activity of mitochondrial CPT-1 and thyroid hormones in treated animals. The circulating levels of NPY and IGF-1 were decreased with marginal increase in leptin and CCK, in case of treated rats. There was no change in blood glucose and insulin levels were not affected significantly. The hormonal and metabolic changes due to treatment with the H. gordonii extract may be responsible for its anorectic activity.     

The effect of active hexose correlated compound in modulating cytosine arabinoside-induced hair loss,and 6-mercaptopurine- and methotrexate-induced liver injury in rodents

Background: Active hexose correlated compound (AHCC) (a mixture of polysaccharides, amino acids, lipids and minerals derived from cultured mycelia of a Basidiomycete mushroom, Lentinula edodes) was used to assess amelioration of alopecia (hair loss) caused by cytosine arabinoside (Ara-C) and modulation of liver injury caused by single doses 6-mercaptopurine (6-MP) plus methotrexate (MTX). Methods: Follicular integrity and hair growth was assessed in male and female SD neonatal rats (8 days old) treated with a single dose of Ara-C (30 mg/kg/day, i.p.) and AHCC (500 mg/kg/day, p.o.) for 7 consecutive days. The side effects of a single oral dose of 6-MP (2.5 mg/kg body weight) plus MTX (30 mg/kg body weight) and their amelioration by treatment with AHCC (1000 mg/kg body weight) for 28 days were assessed in male ddY mice (8 weeks old). Results: Of the Ara-C treated rats 71.4% showed severe alopecia and 28.6% showed moderate alopecia. However, the AHCC (p.o.)-treated Ara-C group was significantly protected from alopecia. Ara-C treated rats had profound loss of hair follicles but the Ara-C plus AHCC-treated group had mild losses of follicles. AHCC supplementation to the 6-MP- and MTX-treated mice significantly increased body weight, erythrocytes, leukocytes and serum albumin, improved liver hypertrophy and degeneration, normalized the activities of serum glutamic oxaloacetic transaminase (sGOT) and serum glutamic pyruvic transaminase (sGPT), and enhanced liver drug-metabolizing enzymes. Conclusion: Co-administration of AHCC significantly reduced the side effects associated with Ara-C, 6-MP and MTX. However, the molecular mechanism for AHCC activity and its clinical integrity for use needs defining.     

Effects of Canarium odontophyllum leaves on plasma glucose and T lymphocyte population in streptozotocin-induced diabetic rats

Type 1 diabetes mellitus is a chronic disease characterized by lack of insulin production. Immune mechanisms are implicated in the pathogenesis of Type 1 diabetes. Canarium odontophyllum (CO) fruits and leaves have been shown to possess high antioxidant activity. This study was conducted to evaluate the effects of CO leaves aqueous extract on the blood glucose and T lymphocyte population in the spleen of streptozotocin (STZ)-induced diabetic rats. Nineteen male Sprague–Dawley rats were randomly divided into three groups: normal, diabetic control and CO treated diabetic groups. Diabetes was induced by a single intraperitoneal injection of 65 mg STZ/kg body weight. The extract of CO leaves was administered orally by force feeding daily at the dose of 300 mg/kg for 28 days. The rats were sacrificed at the end of the study and the spleen was harvested for flow cytometry analysis. The results showed a significant decrease in body weight of diabetic and CO treated diabetic groups compared with the normal group (p < 0.05). The fasting blood glucose level of CO treated diabetic group was significantly lower than the diabetic group (p < 0.05). Diabetic and CO treated diabetic groups showed a significant increase in the percentage of spleen CD3⁺ CD4⁺ T lymphocytes (p < 0.05) when compared with the normal group. However, there was no significant difference in the percentage of spleen CD3⁺ CD8⁺ T lymphocytes among all experimental groups. The finding suggested that an aqueous extract of CO leaves has the ability to reduce blood glucose levels in diabetic rats.     

Acute toxicity of Orthosiphon stamineus Benth standardized extract in Sprague Dawley rats

The acute toxicity of standardized extract of Orthosiphon stamineus was studied in Sprague Dawley rats. The rats were administered a single dose of 5000 mg/kg body weight (BW) orally on Day 0 and observed for 14 days. There were no deaths recorded and the animals did not show signs of toxicity during the experimental period. The effect of the extract on general behavior, BW, food and water intake, relative organ weight per 100 g BW, hematology and clinical biochemistry were measured. All the parameters measured were unaffected as compared to the control. The acute toxicity LD₅₀ was estimated to be >5000 mg/kg BW.     

Seasonal variations in the body composition and bioaccumulation of heavy metals in Nile tilapia collected from drainage canals in Al-Ahsa,Saudi Arabia

The body composition of Nile tilapia (Oreochromis niloticus) collected from drainage canals in Al-Ahsa, Saudi Arabia and the concentration of four heavy metals; zinc (Zn), cadmium (Cd), cobalt (Co) and lead (Pb) in both fish muscles and the water collected from this environment were assessed across the four seasons. The body composition was found to change with the seasons, with the best body composition being recorded in autumn and winter, where higher levels of protein (17.24, 17.65%), and fat (0.58, 0.71%) and lower water content (80.15, 79.86%) respectively were noted. The concentration of heavy metals in both fish muscles and the water body also varied significantly with the seasons. In the fish muscles, the highest content of Zn (0.409 mg/kg dry weight) and Cd (4.140 mg/kg dry weight) was recorded in winter, however, the highest concentration of Co (0.318 mg/kg dry weight) and Pb (1.96 mg/kg dry weight) was observed in spring and summer respectively. On the other hand, the water samples collected in autumn showed the maximum concentration of Cd (1.385 mg/L), Co (0.762 mg/L) and Pb (0.18 mg/L) however, the maximum concentration of Zn (0.0041 mg/L) was recorded in winter. With the exception of Cd, the accumulation of the studied heavy metals in fish muscles was within the safe limits for seafood recommended by various organizations.     

Astragaloside IV ameliorates renal injury in streptozotocin-induced diabetic rats through inhibiting NF-κB-mediated inflammatory genes expression

Accumulating evidence suggests that inflammatory processes are involved in the development of diabetic nephropathy (DN). However, there are no effective interventions for inflammation in the diabetic kidneys. Here, we tested the hypothesis that Astragaloside IV(AS-IV), a novel saponin purified from Astragalus membranaceus (Fisch) Bge, ameliorates DN in streptozotocin (STZ)-induced diabetic rats through anti-inflammatory mechanisms. Diabetes was induced with STZ (65 mg/kg) by intraperitoneal injection in rats. Two weeks after STZ injection, rats were divided into three groups (n = 8/each group), namely, diabetic rats, diabetic rats treated with AS-IV at 5 and 10 mg kg^?1 d^?1, p.o., for 8 weeks. The normal rats were chosen as nondiabetic control group (n = 8). The rats were sacrificed 10 weeks after induction of diabetes. AS-IV ameliorated albuminuria, renal histopathology and podocyte foot process effacement in diabetic rats. Renal NF-κB activity, as wells as protein and mRNA expression were increased in diabetic kidneys, accompanied by an increase in mRNA expression and protein content of TNF-α, MCP-1 and ICAM-1 in kidney tissues. The α₁-chain type IV collagen mRNA was elevated in the kidneys of diabetic rats. All of these abnormalities were partially restored by AS-IV. AS-IV also decreased the serum levels of TNF-α, MCP-1 and ICAM-1 in diabetic rats. These findings suggest that AS-IV, a novel anti-inflammatory agent, attenuated DN in rats through inhibiting NF-κB mediated inflammatory genes expression.     

Growth performance and starch utilization in common carp (Cyprinus carpio L.) in response to dietary chromium chloride supplementation

A nutrition trial was conducted on juvenile common carp (Cyprinus carpio), initial mean body weight 15 ± 0.4 g within a controlled facility at 25 ± 0.5 °C. Six diets containing various levels of supplementary Cr (0, 0.2, 0.5, 1.0, 1.5, and 2.0) mg Cr/kg of diet as Cr chloride hexahydrate were fed to carp for a period of 10 weeks. Lower growth performance was observed in fish fed on the control diet and the diet supplemented with the highest level of Cr (2.0 mg Cr/kg). Although fish fed 0.5 mg Cr/kg showed the best growth performance, this was not significantly different (P > 0.05) from fish fed 1.0 mg Cr/kg. The regression of plasma glucose concentration was linear (R² = 0.97 and P value = 0.001) as the Cr content of the diet increased (up to 1.5 mg Cr/kg).Cr carcass content was elevated with an increasing level of dietary Cr supplementation up to 1.5 mg Cr/kg; but fish fed on the diet supplemented with the highest level of Cr (2.0 mg Cr/kg) showed a decrease in Cr carcass content.Histological examination to evaluate the impact of different Cr supplementation on liver and gut tissues showed notable changes. The higher level of Cr (2.0 mg Cr/kg) in the diet gave rise to elevated hepatocyte vacuolization and changes in gut tissue morphology.It appeared that Cr chloride significantly improved growth within a defined range (0.2–1.5) mg Cr/kg without any negative impact, while 2.0 mg Cr/kg in carp diet seems to be the threshold for the initiation of toxicity.     

Effect of Bacopa monniera on liver and kidney toxicity in chronic use of opioids

In the present study, we investigated the protective effect of Bacopa monniera, an indigenous Ayurvedic medicinal plant in India, against morphine-induced liver and kidney toxicity in rats. Morphine intoxicated rats received 10-160 mg/kg body weight of morphine hydrochloride intraperitoneally for 21 days. Bacopa monniera Extract (BME) pretreated rats were administered with BME (40 mg/kg) orally once a day 2 h before the injection of morphine for 21 days. Pretreatment with BME has shown to possess a significant protective effect against morphine-induced liver and kidney functions in terms of serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, alkaline phosphatase, lactate dehydrogenases and gamma-glutamyl transferase activities and urea, creatinine and uric acid level respectively. Histopathological changes of liver and kidney were also in accordance with the biochemical findings. The results of this study indicate that Bacopa monniera extract exerted a protection against morphine-induced liver and kidney toxicity.     

Supplementation of selenium reduces chemical hepatocarcinogenesis in male Sprague-Dawley rats

Selenium is an essential micronutrient mineral found mainly in soils and has been shown to prevent certain cancers in humans and animals. However, the dose and effects of selenium on liver cancer are controversial. The aim of this study was to investigate the effects of sodium selenite (4 mg/kg in drinking water) on chemically induced hepatocarcinogenesis in rats. Hepatocarcinogenesis was induced by a single intraperitoneal injection of diethyl nitrosamine (DEN) (200 mg/kg body weight) and 2 weeks later, the carcinogenic effect was promoted by 2-acetylaminofluorene (2-AAF) (0.02%). 44 Sprague-Dawley rats were divided into 6 groups: negative control, positive control (DEN+2-AAF), pre-selenium group (sodium selenite for 4 weeks, then DEN+2-AAF), pre-selenium control group (sodium selenite for 4 weeks, no DEN or 2-AAF), post-selenium group (sodium selenite for 8 weeks after 4 weeks of DEN injection) and post-selenium control group (sodium selenite for 8 weeks, no DEN or 2-AAF). Hematoxylin and eosin plus Gordon and Sweet’s methods were used to stain liver tissues. The results showed that the number and sizes of hepatic nodules in pre- and post-selenium treatment groups significantly decreased (P<0.05) compared with the positive control. Microscopic analysis of pre- and post-selenium groups showed that the majority of nodules were hyperplastic with preserved liver architecture, whereas the positive control was full of neoplastic nodules with a completely disrupted liver architecture. Hence, pre- and post-selenium treatments can reduce the extent of liver cancer on chemically induced hepatocarcinogenesis in rats.     

Hypoglycemic activity of a polyphenolic oligomer-rich extract of Cinnamomum parthenoxylon bark in normal and streptozotocin-induced diabetic rats

Cinnamon bark has been reported to be effective in the alleviation of diabetes through its antioxidant and insulin-potentiating activities. The water-soluble polyphenolic oligomers found in cinnamon are thought to be responsible for this biological activity. In this study, the hypoglycemic activity of a polyphenolic oligomer-rich extract from the barks of Cinnamomum parthenoxylon (Jack) Nees was studied in normal, transiently hyperglycemic, and streptozotocin (STZ)-induced diabetic rats. Oral administration of the extract at doses of 100, 200, and 300 mg/kg body wt. caused significant changes in body weight loss and fasting blood glucose levels of normal rats. In STZ-induced diabetic rats, after administration of the extract at doses of 100, 200, and 300 mg/kg body wt. over 14 days, the blood glucose levels were decreased by 11.1%, 22.5%, and 38.7%, respectively, and the plasma insulin levels were significantly increased over pre-treatment levels. In an oral glucose tolerance test, the extract produced a significant decrease in glycemia 90 min after the glucose pulse. These results suggest that Cinnamomum parthenoxylon polyphenolic oligomer-rich extract could be potentially useful for post-prandial hyperglycemia treatment.     

Xanthohumol lowers body weight and fasting plasma glucose in obese male Zucker fa/fa rats

Obesity contributes to increased risk for several chronic diseases including cardiovascular disease and type 2 diabetes. Xanthohumol, a prenylated flavonoid from hops (Humulus lupulus), was tested for efficacy on biomarkers of metabolic syndrome in 4 week old Zucker fa/fa rats, a rodent model of obesity. Rats received daily oral doses of xanthohumol at 0, 1.86, 5.64, and 16.9 mg/kg BW for 6 weeks. All rats were maintained on a high fat (60% kcal) AIN-93G diet for 3 weeks to induce severe obesity followed by a normal AIN-93G (15% kcal fat) diet for the last 3 weeks of the study. Weekly food intake and body weight were recorded. Plasma cholesterol, glucose, insulin, triglyceride, and monocyte chemoattractant protein-1 (MCP-1) levels were assessed using commercial assay kits. Plasma and liver tissue levels of XN and its metabolites were determined by liquid–chromatography tandem mass spectrometry. Plasma and liver tissue levels of xanthohumol were similar between low and medium dose groups and significantly (p < 0.05) elevated in the highest dose group. There was a dose-dependent effect on body weight and plasma glucose levels. The highest dose group (n = 6) had significantly lower plasma glucose levels compared to the control group (n = 6) in male but not female rats. There was also a significant decrease in body weight for male rats in the highest dose group (16.9 mg/kg BW) compared to rats that received no xanthohumol, which was also not seen for female rats. Plasma cholesterol, insulin, triglycerides, and MCP-1 as well as food intake were not affected by treatment. The findings suggest that xanthohumol has beneficial effects on markers of metabolic syndrome.     

A phytosterol enriched refined extract of Brassica campestris L. pollen significantly improves benign prostatic hyperplasia (BPH) in a rat model as compared to the classical TCM pollen preparation Qianlie Kang Pule’an Tablets

In Qinghai Province, the Brassica campestris L. pollen preparation Qianlie Kang Pule’an Tablet (QKPT) is traditionally used for BPH therapy. However, in QKPT the content of supposedly active phytosterols is relatively low at 2.59%, necessitating high doses for successful therapy. Therefore, a phytosterol enriched (4.54%) refined extract of B. campestris pollen (PE) was developed and compared with QKPT in a BPH rat model. Six groups of rats (n = 8 each), namely sham-operated distilled water control, castrated distilled water control, castrated QKPT 2.0 g/kg, castrated PE 0.1 g/kg, castrated PE 0.2 g/kg, and castrated PE 0.4 g/kg, were intragastrically treated with the respective daily doses. Testosterone propionate (0.3 mg/day) was administered to all castrated rats, while the sham-operated group received placebo injections. After 30 days, the animals were sacrificed and prostates as well as seminal vesicles excised and weighted in order to calculate prostate volume index (PVI) as well as prostate index (PI) and seminal vesicle index (SVI), defined as organ weight in g per 100 g body weight. Compared with sham-operated controls, PI (p < 0.01), PVI (p < 0.01), and SVI (p < 0.01) were all significantly increased in all castrated, testosterone treated rats. After treatment with PE at 0.4 and 0.2 g/kg or QKPT at 2.0 g/kg per day, both indices were significantly reduced (p < 0.01) as compared to the castrated distilled water control. For PE at 0.1 g/kg per day only PI was significantly reduced (p < 0.05). At the highest PE concentration of 0.4 g/kg per day both PI and SVI were also significantly reduced when compared to the QKPT group (p < 0.05). Both PE and QKPT demonstrated curative effects against BPH in the applied animal model. In its highest dose at 0.4 g/kg per day, PE was clearly superior to QKPT.     

Chromium picolinate attenuates hyperglycemia-induced oxidative stress in streptozotocin-induced diabetic rats

Chromium picolinate is advocated as an anti-diabetic agent for impaired glycemic control. It is a transition metal that exists in various oxidation states and may thereby act as a pro-oxidant. The present study has been designed to examine the effect of chromium picolinate supplementation on hyperglycemia-induced oxidative stress. Diabetes was induced in male Wistar rats by a single intraperitoneal injection of streptozotocin (50 mg/kg body weight) and chromium was administered orally as chromium picolinate (1 mg/kg body weight) daily for a period of four weeks after the induction of diabetes. As is characteristic of diabetic condition, hyperglycemia was associated with an increase in oxidative stress in liver in terms of increased lipid peroxidation and decreased glutathione levels. The activity of antioxidant enzymes like superoxide dismutase, catalase and glutathione reductase were significantly reduced in liver of diabetic animals. Levels of α-tocopherol and ascorbic acid were found to be considerably lower in plasma of diabetic rats. Chromium picolinate administration on the other hand was found to have beneficial effect in normalizing glucose levels, lipid peroxidation and antioxidant status. The results from the present study demonstrate potential of chromium picolinate to attenuate hyperglycemia-induced oxidative stress in experimental diabetes.     

Effect of two selenium sources on hepatocarcinogenesis and several angiogenic cytokines in diethylnitrosamine-induced hepatocarcinoma rats

This experiment was designed to compare the effect of two selenium sources at the dosage of therapeutic level on hepatocarcinogenesis and angiogenic cytokines in DEN-induced hepatocarcinoma rats to further approach their possible anticancer's mechanism. One hundred and seventy-eight Sprague-Dawley (SD) rats (average weight being 100–120 g) were randomly divided into 5 groups (I–V). Animals in group I, group II and group III served as the negative control, sodium selenite control (SS) and positive controls respectively, and received 0.1, 3.0, and 0.1 mg/kg selenium from sodium selenite supplemented diets during the whole experimental time. Rats in group IV and group V were fed with selenium from selenium-enriched malt (SEM) and sodium selenite (SS) supplemented diets (3 mg/kg respectively). To balance the nutritional content among each group, normal malt which was not treated with selenium was added into the diets of the challenge groups. The nutrition contents, except the selenium of the diet in each group, were similar and in accordance with NRC standards. Rats in groups III–V were treated by aqueous diethylnitrosamine solution (100 mg/L) at the dosage of 10 mg/kg body weight every day for 16 weeks to induce hepatocarcinoma, and drank sterilized water for an additional two weeks. Rats in group I and group II drank sterilized water throughout the experiment. At 4th, 8th, 12th, 16th week, five rats in each group were then sacrificed by cervical decapitation. At the termination of the study, at 18th week, the surplus rats were sacrificed by cervical decapitation. Feed was withheld from the rats for 12 h before sampling. The number of hepatoma nodules in liver and mortality of rats were calculated. The values of the following items, including α-fetoprotein (AFP), gamma-glutamyltranspeptidase (GGT), tumor necrosis factor-α (TNF-α), insulin-like growth factors-II (IGF-II), nitric oxide (NO) and total nitric oxide synthase (T-NOS) in plasma were determined. At the same time, the positive numbers of vascular endothelial growth factor (VEGF) and protein kinase C-α (PKCα) staining cells in tumor tissue were analyzed by immunohistochemistry using the Envision two step methods with a kit. The results indicated that SEM could significantly decrease the mortality of rats and the number of hepatoma nodules, values of GGT and AFP, and the levels of IGF-II, NO and NOS and lessen the positive numbers of VEGF and PKCα staining cells in tumor tissue. Moreover, SEM could increase the levels of TNF-α in the initiated time of hepatocarcinogenesis, whereas, decrease the levels of TNF-α in the progressive time of hepatocarcinogenesis. SS could only significantly inhibit the positive numbers of PKCα staining cells in tumor tissue, decrease the levels of GGT, AFP and TNF-α at minority sampling times, and increase the levels of NO. In conclusion, SEM could reduce the mortality. It might be related to deaden significantly the lesion of liver, delay the cause of hepatocarcinogenesis, and inhibit the progress of angiogenesis to increase the livability of DEN-induced hepatocarcinoma rats. SS at the same therapeutic dosage had less effect on the hepatocarcinogenesis by inhibiting angiogenesis and relative cytokines to some extent.     

Trace mineral status and liver and blood parameters in sheep without mineral supply compared to local roe deer (Capreolus capreolus) populations

General health, clinical-chemical blood analysis and copper (Cu), zinc (Zn), selenium (Se) and vitamin E concentrations in plasma and liver tissue (wet weight, ww) of two extensive grazing sheep flocks without mineral supply were compared to the status of local roe deer (Capreolus capreolus) populations (liver samples). Both sheep flocks were classified as healthy except for a remarkable variation in body weight and a slight foot rot infection in one flock. Hematology of sheep was normal, and total protein and creatinine as well as activities of creatin kinase, aspartat-amino-transferase, alkaline phosphatase and gamma-glutamyl-transferase in plasma were within reference levels. The mean of glutamate dehydrogenase (13.8 U/l) was slightly elevated in one flock. Mean liver concentrations of Zn (38.9 and 43.5 mg/kg ww) and Cu (111 and 87.5 mg/kg ww) in sheep flocks were higher compared to the respective roe deer populations (27.5 and 36.3 mg Zn/kg ww; 18.3 and 28.6 mg Cu/kg ww). This is supposed to be caused by differences in Cu and Zn metabolism in sheep and roe deer. Selenium deficiency was diagnosed in liver samples of both sheep flocks (0.21 and 0.23 mg/kg ww). There were neither significant differences compared to roe deer (0.21 and 0.27 mg Se/kg ww) nor differences depending on location. Correlations between plasma and liver concentrations of Cu, Zn and Se were not significant in sheep. Means of vitamin E in liver samples (30.6 and 41.8 mg/kg ww) were higher in roe deer populations. This may be caused by the opportunity of selective browsing for wild ruminants, which allows access to younger plants which are higher in vitamin E.