Effect of parachlorophenylalanine,a brain serotonin depletor,on the prolactin cells of the eel pituitary

Summary Parachlorophenylalanine (pCPA), an inhibitor of tryptophan hydroxylase depleting brain serotonin in higher vertebrates, was injected into freshwater eels. After 4 or 6 injections (200 mg/kg/day) or 10 injections (100 and 140 mg/kg/day) plasma electrolyte values were not modified. Prolactin (PRL) cells appear less active, with increased granulation after 6 and 10 injections. Their cell height (P < 0.01) and their nuclear area (P < 0.001) are reduced. As injections of 5-hydroxytryptophan stimulate PRL cells, these findings suggest that a serotoninergic system may participate in the regulation of PRL cell activity. Brain serotonin depletion probably decreases granule release in PRL cells, a result comparable to the lowering action of pCPA on the plasma PRL level in some mammals.     

Antiestrogen therapies affect tissue homeostasis of the gerbil (Meriones unguiculatus) female prostate and ovaries

The present work aims to evaluate the response of the adult gerbil female prostate (paraurethral glands) and ovaries to short-term exposure to antiestrogenic agents, consisting of daily oral doses of letrozole (1 mg kg(-1) day(-1)) or intradermal doses of tamoxifen (1 mg/kg) every other day for 21 days. The serum levels of testosterone and estradiol were monitored, and the prostates and ovaries collected for structural, ultrastructural, and immunocytochemical analyses. The letrozole treatment resulted in increases of serum testosterone levels and secretory activity as well as in glandular hyperplasia and dysplastic growth, simulating the effects caused by the exogenous androgens. The effects caused by tamoxifen indicate that this endocrine agent acted as an estrogenic agonist on the prostate, causing glandular hypertrophy, secretory activity decrease, and the development of prostatic lesions. Therefore, it is possible to conclude that the letrozole and tamoxifen therapies result in a series of complex effects that endanger the physiology of hormone-dependent organs, including the female prostate and ovaries. The hormonal imbalance caused by administration of these drugs resulted in considerable changes in prostatic morphology, in a manner very similar to what occurs during the development of prostatic lesions in aged postmenopausal women. Thus, these therapies must be chosen carefully since long-term treatments can result in female prostate dysplasic lesions.     

Amiodarone inhibits interleukin 6 production and attenuates myocardial injury induced by viral myocarditis in mice

A recent study has shown that amiodarone inhibits the production of cytokines in vitro. This study was performed to examine the effects of amiodarone on survival, heart weight-to-body-weight ratio (HW/BW), myocardial lesions and cytokines production in a murine model of viral myocarditis induced by the encephalomyocarditis virus (EMCV). Four-week-old male DBA/2 mice were inoculated with the EMCV. To examine its effect on survival and HW/BW on day 14, mice were administered oral amiodarone (30 mg/kg) or the vehicle only once daily, starting 4 days before inoculation of the virus. The effects of amiodarone on histopathologic changes in myocardial lesions and myocardial cytokine production were studied in mice treated with amiodarone (10 mg/kg or 30 mg/kg) or vehicle, and killed day 7. The survival rate on day 14 was significantly higher in the amiodarone-treated mice than in the control mice. The HW/BW, histopathologic score of cellular infiltration and myocardial interleukin 6 concentration were significantly lower in the amiodarone-treated group than in the control group. Likewise, myocardial necrotic area was significantly smaller in the amiodarone group than in the control group. This study suggests that the beneficial effects of amiodarone in viral myocarditis may be mediated by decreasing interleukin 6 production in myocardial tissue.     

Morphological alterations in distal and collecting tubules of the rat renal cortex after aminoglycoside administration at low doses

Ultrastructural alterations in the cortical, distal and collecting tubules have been examined in female Sprague-Dawley rats treated with various aminoglycosides in clinical use. Gentamicin, dibekacin (10 mg/kg X day), netilmicin, tobramycin (4 or 10 mg/kg X day) or amikacin (37.5 mg/kg X day) were administered intraperitoneally twice a day over different periods of time, extending from 4 to 14 days. The kidney cortex was examined after 4, 7, 10 or 14 days of aminoglycoside administration by light (semithin sections) and electron microscopy. After 7 or more days of treatment, lysosomes in collecting tubular cells (and to a lesser extent in distal tubular cells) contained concentric lamellar material (myeloid bodies), an ultrastructural alteration typical of drug-induced lysosomal phospholipidosis. Although this alteration appeared qualitatively similar to that observed in proximal tubular cells, it was less conspicuous and occurred later during treatment. In addition, distal tubular cells occasionally showed marked vacuolization and disruption of the basal cell architecture. The possible relationship between these alterations and the urine hypo-osmolality characteristic of aminoglycoside-induced renal dysfunction is discussed.     

Role of natural killer cells in the modulation of primary antibody production by purine nucleosides and their analogs.

Previous results from this laboratory demonstrated that treatment of mice with the adenosine analog tubercidin (Tub) reduced natural killer (NK) cell activity while stimulating antibody production whereas the deoxyadenosine analog, 2-fluoroadenine arabinoside-5'-monophosphate (FaraAMP), produced opposite effects; i.e., it stimulated NK cell activity at doses that inhibited antibody formation (Cancer Res. 48, 4799, 1988). Since NK cells have been reported to play a suppressor role in immunoglobulin induction, it was hypothesized that the actions of Tub and FaraAMP on antibody production occurred secondary to their opposing effects on NK cells. To test this hypothesis, abilities of these nucleoside analogs to modulate primary antibody response to sheep red blood cells were evaluated in a C57BL/6 mutant mouse lacking NK cell activity (the beige mutation. C57BL/6-bg/bg). As previously found with C3H/He mice. NK cell activity was inhibited (Tub, doses 2-6 mg/kg/day for 3 days) or stimulated (FaraAMP, doses 75-250 mg/kg/day for 3 days) in heterozygous mice C57BL/6-bg/+. In support of the hypothesis, these nucleosides had no effect on primary antibody formation in the homozygous mutant mice at doses that clearly stimulated (Tub) or inhibited (FaraAMP) this immune response in heterozygous C57BL/6-bg/+ animals. This results was corroborated in C57BL/6 wild-type mice by abrogation of NK cell activity using a monoclonal antibody to the NK cell surface glycophisingolipid, ganglio-n-tetraosylceramide. We conclude that under the conditions of drug administration, modulation of primary antibody formation by Tub and FaraAMP in mice occurs indirectly via NK cells. Similar experiments using the potent ADA inhibitor, deoxycoformycin, indicated that its enhancement of primary antibody formation is independent of NK cell activity.     

Hepatic actions of levonorgestrel: correlations between biochemical and morphological findings

The influence of the synthetic sexual steroid levonorgestrel (LN) on rat liver in various doses and at different structural levels was investigated. A slight reactive hepatosis was found by histological examination after administration of LN in a dose of 10 mg per kg body wt. The same dose caused exclusively distinct lesions of the mitochondria, however, only in centrilobular parenchymal cells, whereas in the periportal hepatocytes only the lipid droplet content appears somewhat elevated. LN decreased the total glutathione content of the liver. The mitochondrial glutathione was decreased more intensively. One mg/kg body wt. of LN decreased the cytochrome P-450 content, but 10 mg/kg body wt. increased ethyl-morphine N-demethylation and 7-ethoxycoumarin O-deethylation activities. Distinct correlations could be shown between the biochemical changes and the ultrastructural findings.     

Losartan, a nonpeptide angiotensin II (Ang II) receptor antagonist, inhibits neointima formation following balloon injury to rat carotid arteries.

Angiotensin-converting enzyme inhibitors have been shown to inhibit intimal thickening following balloon catheterization of rat carotid arteries. To assess the role of the renin-angiotensin pathway and the angiotensin type-I (AT1) receptor in this effect, the nonpeptide Ang II antagonist losartan (DuP 753) or vehicle was infused continuously i.v. in rats from two days before to two weeks after balloon injury to the left common carotid artery; drug effects upon intimal thickening were examined histologically. Losartan produced a dose-dependent reduction in cross-sectional area of intimal lesions determined two weeks post balloon injury. At 5 mg/kg/day a nonsignificant 23% reduction of intimal area was observed. At the higher dose of 15 mg/kg/day, losartan produced a 48% reduction in intimal area (P less than 0.05) compared to the vehicle-infused group. The cellular density of the neointima was not affected by losartan, indicating a probable effect of the drug upon migration and/or proliferation of smooth muscle cells. In separate groups of non-ballooned rats, losartan infusions of 5 and 15 mg/kg/day produced significant rightward shifts (averaging 6.4- and 55-fold, respectively) in curves relating increases in blood pressure to intravenous Ang II in pithed rats determined between 2 and 16 days following initiation of losartan infusion. Mean arterial blood pressure (determined under alpha-chloralose anesthesia) was reduced following continuous losartan infusion for 6 days from 128 +/- 8 mm Hg (vehicle) to 105 +/- 8 mm Hg at 5 mg/kg/day (P less than 0.05), and 106 +/- 4 mm Hg at 15 mg/kg/day (P less than 0.05). Thus, losartan attenuated the vascular response to balloon catheter injury, and this effect was associated with functional block of vascular AT1 receptors. The results support a role for Ang II, acting via AT1 receptors, in myointimal thickening subsequent to balloon injury of rat carotid arteries.     

Abortifacient principle of Achyranthes aspera Linn

Achyranthes apsera is an abundant indigenous herb in India. Extracts of the whole plant had shown an abortifacient effect in mice. Maximal activity was in the benzene extract which was tested. The drug, in olive oil, was given orally to rabbits in doses of 50 mg/kg of body weight on the 8th day postcoitum. Laparotomy was done on the 11th day. No implantation sites were found. However, ovaries contained prominent corpus luteum, indicating that the drug had prevented pregnancy. In rats, the drug was given orally as a single dose of 50 mg/kg of body weight on the 6th or 7th day after mating. No effect was observed. In mice the drug was given at a single dose of either 10, 15, 25, or 50 mg/kg of body weight. For toxicity tests in mice, a single dose of 1000 mg/kg of body weight was given. After 1 month animals were autopsied and the organs examined. The drug was nontoxic. For a chronic toxicity test 75 mg/kg of body weight was given every 21 days. After 6 months of drug treatment, blood and tissue samples were examined. No toxic effects were observed. For a teratogenic study, 15 mated female mice were fed 10 or 25 mg/kg of body weight on Day 6 of gestation. 3 generations of offspring showed no malformations. In mice, abortifacient effects were noted with a maximum activity at 50 mg/kg of body weight. The drug showed no estrogenic, antiestrogenic, or androgenic effects in mice. Progesterone or pituitary extract given along with the drug did not prevent abortions in mice. The drug was species-specific in that no abortifacient effect was found in rats.     

Chronic disturbances in NO production results in histochemical and subcellular alterations of the rat heart

The mechanisms and myocardial alterations associated with NO-deficient hypertension are still far from clear. The aim of the present study was to focus on the enzyme histochemical and subcellular changes in the heart of L-NAME treated rats, as well as to examine the influence of captopril treatment. Wistar rats were administered either L-NAME (40 mg/kg/day) alone or together with captopril (100 mg/kg/day) for a period of 4 weeks. A significant increase of blood pressure confirmed the reliability of the model. The results showed that long-lasting L-NAME administration was accompanied by a decrease of endothelial NO-synthase activity and by a significant local decrease of the following enzyme activities: capillary-related alkaline phosphatase, 5'-nucleotidase and ATPase (but not dipeptidyl peptidase IV) and cardiomyocyte-related glycogen phosphorylase, succinic dehydrogenase, beta-hydroxybutyrate dehydrogenase and ATPases. No activity of these enzymes was found in the scar, whereas a marked increase of alkaline phosphatase and dipeptidyl peptidase IV activities was found in the foci of fibrotization. Histochemical changes correlated with subcellular changes, which were characterized by 1) apparent fibroblast activation associated with interstitial/perivascular fibrosis, 2) heterogeneous population of the normal, hypertrophic and injured cardiomyocytes, 3) enhancement of the atrial granules and their translocation into the sarcolemma, and 4) impairment of capillaries as well as by induction of angiogenesis. Similar alterations were also found in the heart of captopril co-treated rats, despite of the significant suppression of blood pressure. The results indicate that NO-deficient hypertension is accompanied by metabolic disturbances and ultrastructural alterations of the heart and these changes are probably not induced by the renin-angiotension system only.     

The Induction of Phagocytic Activation by Mixtures of the Water Chlorination By‐Products,Dichloroacetate‐ and Trichloroacetate,in Mice after Subchronic Exposure

In this study, groups of B6C3F1 male mice were treated with dichloroacetate (DCA), trichloroacetate (TCA), and mixtures of the compounds (Mix I, II, and III) daily by gavage, for 13 weeks. The tested doses were 7.5, 15, and 30 mg DCA/kg/day and 12.5, 25, and 50 mg TCA/kg/day. The DCA: TCA ratios in Mix I, II, and III were 7.5:12.5, 15:25, and 30:50 mg/kg/day, respectively. Peritoneal lavage cells were collected at the end of the treatment period and assayed for the biomarkers of phagocytic activation, including superoxide anion and tumor necrosis factor‐alpha production, and myeloperoxidase activity. The mixtures produced nonlinear effects on the biomarkers of phagocytic activation, with Mix I and II effects were found to be additive, but Mix III effects were found to be less than additive. © 2013 Wiley Periodicals, Inc. J BiochemMol Toxicol 27:237‐242, 2013; View this article online at wileyonlinelibrary.com . DOI 10.1002/jbt.21476     

Uric acid as an inhibitor of cyclophosphamide-induced micronuclei in mice

Swiss albino male mice, 6-8 weeks old, were treated orally with different doses of uric acid dissolved in water for 7 days. Some of the mice in each group were injected i.p. with cyclophosphamide (25 mg/kg) and killed after 30 h. The blood of all animals was analyzed for uric acid levels. The femoral cells of the mice in different groups were collected and studied. Uric acid was found to be devoid of mitodepressant or clastogenic activity at 10-100 mg/kg/day. Pretreatment with uric acid was found to provide significant protection against cyclophosphamide-induced bone marrow depression and micronucleated polychromatic erythrocytes.     

Morphological changes in the endocrine pancreas of mice after treatment with streptozotocin combined with cyclophosphamide and neurotropin.

The effect of neurotropin (NSP) in combination with streptozotocin (STZ) and cyclophosphamide (CY) on blood glucose and pancreatic histopathology on day 7 and day 14 after the initiation of the treatment was studied in C57Bl/6 male mice. STZ (40 mg/kg) and NSP (1 mg/kg) were applied intraperitoneally on five consecutive days and CY (150 mg/kg)--twice on day 1 and day 3. In single B cells dilatation of the endoplasmic reticulum was found. On day 7 in proximity to some endocrine cells in the mice treated with STZ, STZ + CY + NSP and STZ + CY macrophages were observed. On day 14 lymphocytic infiltration of the islets was demonstrated only in the groups of mice injected with STZ, STZ + CY while in the group treated with the combination STZ + CY + NSP no infiltration was seen. All experimental groups showed no biochemical evidence for hyperglycemia probably due to the mild destruction of a small number of B cells. The results indicate that NSP might possess a restorative action on insulitis induced by multiple low dose streptozotocin administration in mice.     

Influence of recombinant human erythropoietin on neutrophil function in premature neonates

The in vivo influence of recombinant human erythropoietin (rhEpo) and iron on human neutrophil (PMN) antimicrobial function was assessed. A total of 21 preterm infants were randomized to receive either 200 U/kg/other day of rHuEPO+12 mg/kg/day of iron (EPO+high Fe, seven infants) or 200 U/kg/other day of rhEPO+4 mg/kg/day of iron (EPO+standard Fe, 9 infants) or 4 mg/kg/day of iron only (standard Fe, five infants). PMNs were isolated from blood of these infants 60+/-5 days after birth and from eight healthy adults. No differences between infants and adults were found in PMN random migration and chemotactic activity to N-formylmethionyl leucyl phenylalanine (FMLP), superoxide anion production in response to FMLP and phagocytosis of Staphylococcus aureus. In contrast, percentage phagocytosis was significantly lower in EPO+standard Fe as compared to both EPO+high Fe and standard Fe groups (P<0.01). This modest impairment of phagocytic activity of neonatal PMNs found in association with administration of rhEPO and standard iron may be related to consumption of iron during rhEPO-enhanced erythropoiesis.     

Parameters of proliferative activity of hematopoietic cells in mice protected from irradiation by indralin in combination with Zn-metallothionein

One day after the irradiation (dose 6 Gy) of mice protected by the injection of Zn-metallothionein (Zn-MT) in doze 8.6 mg/kg, 10-20 min before irradiation, then alpha-adrenomimetic indraline (150 mg/kg) 5-10 min before irradiation the increase in nucleic cell number, [3H] thymidine incorporation, and antioxidant activity in bone marrow in comparison with the control and indraline per se was revealed. In mice protected according to the scheme: Zn-MT in the same doze, then indraline (100 mg/kg) one day after, and then in 5-10 min exposure to 6 Gy it was found more than 9 times increase of endogeneous CFC in spleen on 8th day while indraline per se raised CFC number only 4.8 times. It was found that Zn-MT reduce the indraline acute toxicity. The data on radioprotective activity of monomeric and polymeric Zn-MT forms are submitted.     

An oral developmental neurotoxicity study of decabromodiphenyl ether (DecaBDE) in rats

BACKGROUND: Decabromodiphenyl ether (DecaBDE; CASRN 1163‐19‐5) is a flame retardant used in a variety of manufactured products. A single oral dose of 20.1 mg/kg administered to mice on postnatal day 3 has been reported to alter motor activity at 2, 4, and 6 months of age. METHODS: To further evaluate these results, a developmental neurotoxicity study was conducted in the most commonly used species for studies of this type, the rat, according to international validated testing guidelines and Good Laboratory Practice Standards. DecaBDE was administered orally via gavage in corn oil to dams from gestation day 6 to weaning at doses of 0, 1, 10, 100, or 1,000 mg/kg/day. Standard measures of growth, development, and neurological endpoints were evaluated in the offspring. Motor activity was assessed at 2 months of age. Additional motor activity assessments were conducted at 4 and 6 months of age. Neuropathology and morphometry evaluations of the offspring were performed at weaning and adulthood. RESULTS: No treatment‐related neurobehavioral changes were observed in detailed clinical observations, startle response, or learning and memory tests. No test substance‐related changes were noted in motor activity assessments performed at 2, 4, or 6 months of age. Finally, no treatment‐related neuropathological or morphometric alterations were found. CONCLUSIONS: Under the conditions of this study, the no‐observed‐adverse‐effect level for developmental neurotoxicity of DecaBDE was 1,000 mg/kg/day, the highest dose tested. Birth Defects Res (Part B) 92:17–35, 2011.© 2011 Wiley‐Liss, Inc.     

Effects of alpha-chlorohydrin on the male reproductive tissues of the Polynesian rat,Rattus exulans

Abstract

Doses of α-chlorohydrin (‘Epibloc’) were administered by gavage to mature male Polynesian rats (Rattus exulans) at 100, 200, and 300 mg per kg body weight. Animals that survived were sacrificed either 1 day or 7 days later for assessment of epididymal and testicular cytology and sperm viability. Two of 10 animals died 6 days after treatment with 100 mg/kg; 1/6 died within 24 h of treatment with 200 mg/kg, though 6/10 died when left for 7 days; 300 mg/kg was lethal to all 3 rats tested. After 1 day, microscopic lesions were observed in the Initial Segment of the epididymis of 4/6 rats dosed with 100 mg/kg and in all 5 of the 200 mg/kg group; however, in only one animal at the higher dose level was the damage severe enough to cause epithelial exfoliation and potential blockage of the lumen. In all the animals that survived for 7 days testicular and epididymal cytology were normal, and viable spermatozoa were present at all levels of the tract. Autopsies revealed no evidence of gross epididymal lesions in any of the animals that died from the drug. We conclude that although α-chlorohydrin causes minor lesions in the epididymis of this feral species, the damage appears to be reversible in animals that survive an acute dose, and the drug cannot be considered an effective chemosterilant, as distinct from a poison.     

Strain differences in the dose-response curves of adrenalectomized, starved-refed rats to dehydroepiandrosterone (DHEA)

The effects of adrenalectomy and dehydroepiandrosterone (DHEA) doses (0, 15, 30, 60, 120 and 240 mg/kg/day ip) on hepatic enzyme activity and lipid content and on the amount of epididymal fat pad lipid were studied in starved-refed BHE and Sprague-Dawley rats. BHE rats had significantly greater relative liver size, glucose-6-phosphate dehydrogenase (G6PD) and malic enzyme (ME) activities, and percentage liver lipid but less epididymal fat pad lipid than Sprague-Dawley rats. Adrenalectomized (ADX) rats consumed significantly less food, gained less weight per day, and had less lipid in their livers and fat pads than intact rats. As the level of DHEA increased from 0 to 240 mg/kg/day there was a significant linear decrease in average daily weight gain, food intake, G6PD activity, and percentage liver lipid. At the 15 mg/kg/day dose, G6PD activity was significantly reduced without reductions in the other parameters measured. At the 120 mg/kg/day dose, however, weight gain, food intake, G6PD activity, and percentage liver lipid were significantly lower than that of the controls. At this dose DHEA treatment reduced food intake by 17% whereas it diminished average daily weight gain and G6PD activity by 30 and 56%, respectively. The 240 mg/kg/day dose of DHEA significantly reduced food intake, weight gain, liver lipid, G6PD activity, and ME activity. Intact and ADX BHE rats reduced their G6PD activity and liver lipid more rapidly than Sprague-Dawley rats as the level of DHEA administered increased. ADX Sprague-Dawley rats receiving DHEA had greater liver lipid content and enzyme activity than their intact counterparts whereas the reverse situation was true in BHE rats. These data indicate that the effect of DHEA on body weight gain, food intake, and hepatic and peripheral adiposity are dependent on the strain of rat, the adrenal status, and the DHEA dose.     

Cytotoxic effects of 6-mercaptopurine on the limb-bud blastemal cells of rat embryos.

On day 12 of pregnancy Wistar rats were each given a single ip injection of 5, 8, 16, 25, or 50 mg/kg 6-mercaptopurine. The embryos were removed 1, 2, 3, 5, 6, 10, 24, 48, or 72 h after injection or on day 20 and studied by light and electron microscopy. After 25 or 50 mg/kg all embryos showed no mineralization in the lower extremities. By electron microscopy condensation, shrinking, and fragmentation of cells in the limb bud blastema could be seen after 5 h. The fragments were phagocytosed and broken down by neighboring cells or remained in the extracellular space. After 25 or 50 mg/kg the damage was so extensive that the number of undamaged cells and of cells transforming into phagocytes was not sufficient to remove the debris or to compensate for the defect by mitotic activity. Epithelial cells, nerves, and blood vessels, show no morphological signs of damage. The "critical period" was the time cartilage just starts developing, i.e., when the blastema begins to differentiate.     

Linagliptin improves insulin sensitivity and hepatic steatosis in diet-induced obesity

Linagliptin (TRADJENTA?) is a selective dipeptidyl peptidase-4 (DPP-4) inhibitor. DPP-4 inhibition attenuates insulin resistance and improves peripheral glucose utilization in humans. However, the effects of chronic DPP-4 inhibition on insulin sensitivity are not known. The effects of long-term treatment (3-4 weeks) with 3 mg/kg/day or 30 mg/kg/day linagliptin on insulin sensitivity and liver fat content were determined in diet-induced obese C57BL/6 mice. Chow-fed animals served as controls. DPP-4 activity was significantly inhibited (67-89%) by linagliptin (P<0.001). Following an oral glucose tolerance test, blood glucose concentrations (measured as area under the curve) were significantly suppressed after treatment with 3 mg/kg/day (-16.5% to -20.3%; P<0.01) or 30 mg/kg/day (-14.5% to -26.4%; P<0.05) linagliptin (both P<0.01). Liver fat content was significantly reduced by linagliptin in a dose-dependent manner (both doses P<0.001). Diet-induced obese mice treated for 4 weeks with 3 mg/kg/day or 30 mg/kg/day linagliptin had significantly improved glycated hemoglobin compared with vehicle (both P<0.001). Significant dose-dependent improvements in glucose disposal rates were observed during the steady state of the euglycemic-hyperinsulinemic clamp: 27.3 mg/kg/minute and 32.2 mg/kg/minute in the 3 mg/kg/day and 30 mg/kg/day linagliptin groups, respectively; compared with 20.9 mg/kg/minute with vehicle (P<0.001). Hepatic glucose production was significantly suppressed during the clamp: 4.7 mg/kg/minute and 2.1 mg/kg/minute in the 3 mg/kg/day and 30 mg/kg/day linagliptin groups, respectively; compared with 12.5 mg/kg/minute with vehicle (P<0.001). In addition, 30 mg/kg/day linagliptin treatment resulted in a significantly reduced number of macrophages infiltrating adipose tissue (P<0.05). Linagliptin treatment also decreased liver expression of PTP1B, SOCS3, SREBP1c, SCD-1 and FAS (P<0.05). Other tissues like muscle, heart and kidney were not significantly affected by the insulin sensitizing effect of linagliptin. Long-term linagliptin treatment reduced liver fat content in animals with diet-induced hepatic steatosis and insulin resistance, and may account for improved insulin sensitivity.     

Ultrastructural evaluation of the effect of endosulfan on mice kidney

In this study, the effect of the endosulfan on mice kidney was investigated at ultrastructural level. Moreover, biochemical analyses (G6PD, CAT, SOD, GSH and MDA) were determined in supernatant of kidney tissue. Endosulfan (13mg/kg/day body weight) was administered orally to mices via intragastric-during 10 days. The presence of mitochondrial degeneration in cytoplasm of proximal convoluted tubule cells were a striking feature. Furthermore, there was lipofuscin granules and membranous structures in some of proximal convoluted tubule cells. In some glomeruli, ultrastructural changes such as fusion in pedicels and focal thickening at glomerular basal membrane were seen. There were cytoplasmic bulges in some distal convoluted tubule cells. The biochemical results of the experimental group were significant when compared to the control. The effect of the endosulfan was mainly on the proximal convoluted tubule cells. Morever, the other parts of the nephron were effected. Thus, this degeneration in kidney may be thought that oxidative stress may play a role to the mediator in changing configuration of cell membrane and seem to account for the morphologic alteration of kidney.