RESUMEN
PURPOSE: In experimental and clinical trials, tamoxifen (TAM) has been shown to increase radiation-induced lung fibrosis (RILF). Furthermore, aromatase inhibitors (AI) have been shown to be superior to TAM in the adjuvant setting and preclinical data suggest that letrozole (LET) sensitizes breast cancer cells to ionizing radiation in other studies. In this experimental study, we evaluated whether AI have any impact on the development of RILF in rats. MATERIALS AND METHODS: 60 female wistar- albino rats were divided into 6 groups: Control (group A), RT alone (group B), RT + TAM (group C), RT + anastrozole (ANA group D), RT + LET (group E), and RT + exemestane (EXE, group F). RT consisted of 30 Gy in 10 fractions to both lungs with an anterior field at 2 cm depth. Equivalent doses for 60 kg adult dose per day of TAM, ANA, LET, and EXE were calculated according to the mean weight of rats and orally administrated with a feeding tube. Percentage of lung with fibrosis was quantified with image analysis of histological sections of the lung. The mean score values were calculated for each group. the significance of the differences among groups were calculated using one way ANOVA test and Tukey HSD post-hoc test. RESULTS: Mean values of fibrosis were 1.7, 5.9, 6.7, 2.5, 2 and 2.2 for groups A, B, C, D, E, and F, respectively (p = 0.000). TAM increased RT-induced lung fibrosis but without statistical significance. Groups treated with RT + AI showed significantly less lung fibrosis than groups treated with RT alone or RT + TAM (p = 0.000). RT + AI groups showed nearly similar RT-induced lung fibrosis than control group. CONCLUSIONS: In this study, we found that AI decreased RT-induced lung fibrosis to the control group level suggesting protective effect.
Asunto(s)
Androstadienos/uso terapéutico , Antineoplásicos Hormonales/uso terapéutico , Inhibidores de la Aromatasa/uso terapéutico , Nitrilos/uso terapéutico , Fibrosis Pulmonar/prevención & control , Traumatismos Experimentales por Radiación/prevención & control , Radioterapia/efectos adversos , Triazoles/uso terapéutico , Anastrozol , Animales , Quimioterapia Adyuvante , Femenino , Letrozol , Fibrosis Pulmonar/etiología , Fibrosis Pulmonar/patología , Traumatismos Experimentales por Radiación/etiología , Traumatismos Experimentales por Radiación/patología , Ratas , Ratas Wistar , Tamoxifeno/uso terapéuticoRESUMEN
This study aims to see in an animal experiment how differently the low and high doses of melatonin affect the antioxidant status and peroxidation of lipids. Forty-two male Wistar-Albino rats weighing about 200 gr (180-220) aged 6-7 months were used. Of these rats, 12 were fed with normal rat chow for 12 weeks. The latter ones were divided into two groups, each containing 6 rats. Group 1 (control group) received daily intraperitoneal injections of NaCl (0.9%; w/v). Group 2 was injected ethanol daily (4%; v/v; i.p.) to see the effects of ethanol in which we dissolved melatonin. Thirty rats were fed with a diet enriched with cholesterol (2%; w/w), cholic acid (0.5%; w/w) and propilthyouracil (0.5%; w/w) for 12 weeks. These rats were divided into three groups each containing 10 rats. The low-dose group received melatonin 1 mg/kg/d; i.p. (group 3), the high-dose group received melatonin in a dose of 10 mg/kg/d; i.p. (group 4), and only the cholesterol group did not get any vehicle (group 5). Total cholesterol (TC), LDL cholesterol (LDL-C), total antioxidant capacity (TAC), oxidized LDL (oLDL) and TBARS lelvels were measured in all groups. The produced high-cholesterol diet increased LDL cholesterol. Melatonin decreased the extent of this plasma lipoprotein increase and also prevented the oxidation of it. This effect was clearer when the dose was higher. Antioxidant status seems to be also dose-dependent (Tab. 2, Ref. 33).
Asunto(s)
Antioxidantes/farmacología , Hipercolesterolemia/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Melatonina/farmacología , Animales , Colesterol/sangre , LDL-Colesterol/sangre , Lipoproteínas LDL/sangre , Masculino , Ratas , Ratas WistarRESUMEN
There are no data regarding the late toxicity of trastuzumab (T) administration with radiotherapy (RT). In this experimental study, we aimed to asses if concurrent or sequential administration of T has any impact for the development of radiation-induced pulmonary fibrosis in rats. Fifty-four female Wistar-albino rats were divided into 6 groups. First group of rats (Group 1; concurrent T) had irradiation to whole thoracic region concurrently with T. Second group (Group 2: sequential T-RT) received thoracic irradiation, 1 week after T. Third group (Group 3: sequential RT-T) had thoracic irradiation first and they had T injection 1 week after RT. Fourth group (Group 4: T only) had only T application. Fifth group (Group 5: RT) had only RT. The last group (Group 6: sham) of rats were observed without any application. A single dose of 12 Gy was given to both lungs with an anterior field at 2 cm depth. T dose which was equivalent to 6 mg/kg adult dose was calculated for each rat, and injected by the tail vein. As an end point the extent of pulmonary fibrosis for each field was graded on a scale from 0 (normal lung or minimal fibrous thickening) to 4 (total fibrous obliteration of the field) at histopathological examination. The mean value of fibrosis scores were 1.44, 1.77, 1.75 and 1.62 for Group 1, 2, 3 and 5, respectively, without any statistically significant differences among them (P>0.05). The mean value of fibrosis scores for Group 4 and 6 were 0.25 and 0.33, respectively (P>0.05). When the mean value of fibrosis scores of the groups which had RT with or without T, compared with the observation and the T only groups, the difference was significant (P<0.05) (one-way ANOVA and Tukey HSD post hoc tests) As a conclusion: addition of T to thoracic irradiation either sequentially or concomitantly did not increase radiation-induced pulmonary fibrosis in rats.
Asunto(s)
Anticuerpos Monoclonales/farmacología , Antineoplásicos/farmacología , Fibrosis Pulmonar/tratamiento farmacológico , Fibrosis Pulmonar/etiología , Traumatismos Experimentales por Radiación/tratamiento farmacológico , Animales , Anticuerpos Monoclonales Humanizados , Femenino , Pronóstico , Fibrosis Pulmonar/patología , Traumatismos Experimentales por Radiación/etiología , Ratas , Ratas Wistar , Trastuzumab , Proteína Tumoral Controlada Traslacionalmente 1RESUMEN
BACKGROUND: Curcumin is an anti-oxidant molecule known to be a potent inhibitor of nuclear factor-kappaB (NF-kappaB). It has been shown to attenuate ischemia/reperfusion (I/R) injury in several organ systems. In this study, we sought to investigate the effects of curcumin on the prevention of superior mesenteric artery I/R injury in rats. METHODS: Wistar albino rats were randomly allocated to 3 groups: group I, sham operated (n = 10); group II, I/R injury only (n = 10); group III, curcumin-treated I/R cohort (n = 10). Group I animals underwent laparotomy without I/R injury. After group II animals underwent laparotomy, 60 minutes of superior mesenteric artery ligation were followed by 3 hours of reperfusion. In the curcumin group, 15 days before I/R, curcumin (40 mg/kg) was administered by gastric gavage. All animals were sacrificed at the end of reperfusion. Intestinal tissue samples were obtained to investigate intestinal mucosal injury; in addition we estimated levels of myeloperoxidase (MPO) activity, malondialdehyde (MDA), nitric oxide (NO), glutathione (GSH), interleukin (IL)-6, and tumor necrosis factor (TNF)-alpha. RESULTS: There were statistically significant decreases in GSH levels, along with an increase in intestinal mucosal injury scores, MPO activity, MDA levels, NO, IL-6, and TNF-alpha in group I when compared with groups II and III (P = .01). Curcumin treatment in group III produced a significant increase in GSH levels, as well as a decrease in intestinal mucosal injury scores, MPO activity, MDA, and NO levels when compared with group II (P < .05). CONCLUSION: This study showed that curcumin treatment significantly attenuated reperfusion injury in a superior mesenteric artery I/R model in rats.
Asunto(s)
Curcumina/uso terapéutico , Daño por Reperfusión/prevención & control , Circulación Esplácnica/efectos de los fármacos , Animales , Curcumina/administración & dosificación , Curcumina/farmacología , Modelos Animales de Enfermedad , Lavado Gástrico , Glutatión/metabolismo , Interleucina-6/metabolismo , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/patología , Masculino , Malondialdehído/metabolismo , Óxido Nítrico/metabolismo , Peroxidasa/metabolismo , Ratas , Ratas Wistar , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
OBJECTIVE: Our aim was to clarify the effects of hypercholesterolemic diet and administeration of atorvastatin on lipid peroxidation, protein oxidation and oxidative DNA damage in male New Zealand white rabbits. METHODS: We determined malondialdehyde (MDA), protein carbonyl (PCO) and total thiol (T-SH) levels in plasma and liver tissue, glutathione (GSH) levels in erythrocyte and liver tissue, and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels in plasma. Twenty rabbits were randomly divided into two groups and fed with a high-cholesterol diet (fortified with 1% cholesterol) for 4 weeks. Such rabbits were subjected to either (Group 1) a high-cholesterol diet non-supplemented with atorvastatin (n=10) or (Group 2) a high-cholesterol diet supplemented with atorvastatin (0.3mg atorvastatin per day/kg body weight) for 4 weeks (n=10). A control group (n=5) (Group 3) was fed a cholesterol free diet for 4 weeks. Colorimetric methods were used to determine the level of the oxidative stress markers, except 8-OHdG, which was measured by ELISA. RESULTS: Rabbits were fed with the high-cholesterol diet alone (Group 1) showed higher levels of lipid profile and oxidative protein and DNA damage than compared with dose of the control group (Group 3). Atorvastatin therapy has substantially beneficial effects on oxidative protein and DNA damage in hypercholesterolemic rabbits. CONCLUSIONS: The current findings will, we hope, lead to a new insight into the pathogenesis of atherosclerosis. On the other hand inhibition of protein oxidation and DNA oxidation in the plasma by atorvastatin may be one of the pleiotropic effects of statins, and thus the underlying mechanism needs to be further clarifications.
Asunto(s)
Anticolesterolemiantes/uso terapéutico , Daño del ADN , Ácidos Heptanoicos/uso terapéutico , Hipercolesterolemia/tratamiento farmacológico , Peroxidación de Lípido/efectos de los fármacos , Oxidación-Reducción , Estrés Oxidativo/efectos de los fármacos , Carbonilación Proteica/efectos de los fármacos , Pirroles/uso terapéutico , 8-Hidroxi-2'-Desoxicoguanosina , Animales , Atorvastatina , Desoxiguanosina/análogos & derivados , Desoxiguanosina/sangre , Desoxiguanosina/metabolismo , Glutatión/sangre , Glutatión/metabolismo , Hipercolesterolemia/metabolismo , Hígado/metabolismo , Masculino , Malondialdehído/sangre , Malondialdehído/metabolismo , Conejos , Distribución Aleatoria , Compuestos de Sulfhidrilo/sangre , Compuestos de Sulfhidrilo/metabolismoRESUMEN
Extracts of the medicinal herb Tribulus terrestris (TT) are used for treating various diseases. The saponins, a component of TT, play a role in regulating blood pressure and in treatment of hyperlipidemia. The aim of the study was to investigate the immunohistochemical and ultrastructural alterations in the cerebral cortex of experimental rabbits on a cholesterol rich diet treated with TT. The rabbits were divided into three groups and followed for 12 weeks as control group (CG); experimental group I (EG-I), fed with a cholesterol-rich diet; experimental group II (EG-II), treated with an extract of TT (5 mg/kg/day) after a cholesterol-rich diet of 4 weeks. In EG-I there were ultrastructural changes, including mitochondrial degeneration, increased lipofuscin pigments, myelin sheath damage with axoplasmic shrinkage and electron dense granules in the neurovascular unit. The number of synapses apparently decreased in both experimental groups. Administration of TT extract in EG-II led to marked ultrastructural alterations in neurons, including decreased mitochondrial degeneration (P<0.001) and extensive oedematous areas in the neurovascular unit. However, in EG-II, lamellar myelin, axonal structures and mitochondria were well protected. These alterations possibly indicate that saponins have an effect on the neurons either directly or by its conversion to steroidal saponins. Therefore, these findings add further evidence supporting the protective claims of TT in cerebral architecture in dietary induced hyperlipidemia.
Asunto(s)
Encéfalo/efectos de los fármacos , Neuronas/efectos de los fármacos , Fitoterapia , Extractos Vegetales/farmacocinética , Animales , Encéfalo/patología , Colesterol/toxicidad , Hipercolesterolemia/patología , Inmunohistoquímica , Masculino , Microscopía Electrónica de Transmisión , Vaina de Mielina/efectos de los fármacos , Vaina de Mielina/ultraestructura , Neuronas/patología , Neuronas/ultraestructura , Conejos , Tribulus/químicaRESUMEN
PURPOSE: To assess estrogen-related changes in the redox status of the brain and liver proteins as well as the systemic oxidative stress in ovarectomised (OVX) rats METHODS: Twelve-week-old, sexually mature female Sprague-Dawley rats (200-250g) were randomly divided into four groups: The following treatment combinations were administrated daily to all in 0.05 ml 96% ethanol solution by gastric gavage. (1) Sham operation (2) OVX rats (3) OVX rats [0.02 mg/kg/day of 17beta-estradiol (E2) and 0.01 mg/kg/day of norethisterone acetate] (4) OVX rats [E2 (0.01 mg/kg/day) and drospirenon (0.02 mg/kg/day)]. Estrogen levels were determined using routine clinical-chemistry methods. We also measured protein oxidation parameters such as protein carbonyl (PCO), total thiol (T-SH) and the other oxidative stress markers malondialdehyde (MDA) and glutathione (GSH). RESULTS: Ovariectomy resulted in abnormal elevation of plasma and tissue oxidative stress markers and changes in redox status of the proteins in tissue dependent manner. Supplementation of various estrogens combinations partially alleviated these abnormalities and restored redox homeostasis of proteins after the ovariectomy. Among the studied protein oxidation parameters, plasma and tissue PCO levels of the OVX rats were higher than those of the control groups (P < 0.01). Hormone replacement therapies (HRT) caused a decrease in PCO and MDA in both plasma and tissue of the OVX rats (P < 0.01). HRT in OVX rats decreased plasma MDA and increased liver and brain GSH (P < 0.01). Liver MDA levels of the Drospirenon-treated rats were lower than in the norethisterone acetate group (P < 0.01). On the other hand, Drospirenon increases brain GSH s more effectively than norethisterone acetate (P < 0.01). After bilateral oopherectomy, plasma and tissue T-SH levels decreased in the OVX group compared with control (P < 0.01). Norethisterone acetate increased plasma T-SH more effectively than Drospirenon (P < 0.05) CONCLUSIONS: The study showed the extent of oxidative protein damage (OPD) in this model of estrogen deficiency. The protective effect of estrogens against tissue specific OPD suggests that estrogens play an important role within the antioxidant defense systems in plasma, liver and brain. The exact molecular mechanisms leading to these findings are not yet completely known. Meanwhile, hormone replacement therapy for the prevention of OPD in a tissue specific manner may be required.
Asunto(s)
Estradiol/farmacología , Estrógenos/farmacología , Ovariectomía , Estrés Oxidativo/efectos de los fármacos , Proteínas/metabolismo , Animales , Anticonceptivos Sintéticos Orales/farmacología , Femenino , Glutatión/metabolismo , Malondialdehído/metabolismo , Noretindrona/análogos & derivados , Noretindrona/farmacología , Acetato de Noretindrona , Carbonilación Proteica/efectos de los fármacos , Proteínas/química , Ratas , Ratas Sprague-DawleyRESUMEN
AIMS: To investigate whether the application of vitamin E with or without pentoxifylline could modify the development of radiation-induced pulmonary fibrosis. MATERIALS AND METHODS: Wistar albino rats were supplemented with either vitamin E or pentoxifylline or with both vitamin E and pentoxifylline after a single dose of 14 Gy thoracic irradiation. Supplementation was started the day after irradiation and continued until the rats were sacrificed. As a quantitative end point, the extent of fibrosis was evaluated with a scale from 0 (normal lung) to 8 (total fibrous obliteration of the field) at pathological examination of the lung tissue. RESULTS: A significant reduction in fibrosis was obtained in the group of rats supplemented with vitamin E with or without pentoxifylline, when compared with the group that had irradiation only. CONCLUSION: This experimental study showed that vitamin E supplementation immediately after irradiation protected rats against radiation-induced pulmonary fibrosis. The combination with pentoxifylline was more effective, although pentoxifylline itself had limited efficacy, which was not statistically significant.
Asunto(s)
Antioxidantes/uso terapéutico , Depuradores de Radicales Libres/uso terapéutico , Neoplasias Pulmonares/prevención & control , Neoplasias Inducidas por Radiación/prevención & control , Pentoxifilina/uso terapéutico , Vitamina E/uso terapéutico , Animales , Antioxidantes/administración & dosificación , Suplementos Dietéticos , Quimioterapia Combinada , Femenino , Fibrosis/prevención & control , Depuradores de Radicales Libres/administración & dosificación , Pentoxifilina/administración & dosificación , Dosis de Radiación , Ratas , Ratas Wistar , Vitamina E/administración & dosificaciónRESUMEN
PURPOSE: The presence of hypoxic cells in solid tumors is generally considered as a limiting factor for the complete control of tumors by radiation therapy. Pentoxifylline is a methylxanthine derivative that produces hemorrheologic effects which increase tissue oxygen levels. In this study we aimed to determine whether pentoxifylline would enhance the radiation response of Ehlrich mammary carcinoma in mice. MATERIALS AND METHODS: Ehrlich mammary carcinoma cells were subcutaneously transplanted into the nape of 27 male Balb/c mice. Twelve animals were injected with 50 mg/kg of pentoxifylline intraperitoneally (i.p.) and irradiated 30 min after the administration (study group). Fifteen mice were irradiated without receiving pentoxifylline (control group). All animals were exposed to a single dose of 40 Gy with Co60 gamma rays locally to the tumor site. The effect of pentoxifylline was assessed by the reduxtion rate in tumor volume (mm(3)) which was measured at least 3 times a week until mice were dead. RESULTS: The reduxtion rate of tumor volume on day 4, relative to the initial volume, was 42% in the control group and 61.6% in the study group (p=0.24). The survival of mice in the two groups was not significantly different (p=0.08). CONCLUSION: Although the reduction rate of tumor volume was higher in the study group, the difference was not statistically significant. Pentoxifylline can not be considered as a radiation enhancer in Ehrlich mammary carcinoma.
RESUMEN
In this study, solitary and combined effects of vitamin E and the calcium-channel blocker diltiazem were investigated in streptozotocin (STZ)-induced diabetic rats. Thirty male Wistar albino rats, weighing approximately 200 g were used. Diabetes mellitus was induced by a single intravenous injection of STZ at a dose of 65 mg/kg body weight. Five experimental groups were established as STZ-diabetic, STZ-diabetic + vitamin E, STZ-diabetic + diltiazem and STZ-diabetic + vitamin E + diltiazem. Vitamin E was injected intraperitoneally three times a week at a dose of 500 mg/kg body weight. Diltiazem was given orally every day at a dose of 25 mg/kg body weight. At the end of the study (10 weeks) blood glucose levels of diabetic rats, which had received vitamin E and diltiazem, had significantly decreased when compared with untreated diabetic rats (P < 0.02). Similarly, HbA1c levels had significantly decreased in diabetic rats which had received vitamin E (P < 0.05), diltiazem (P < 0.01) and vitamin E + diltiazem (P < 0.02) when compared with untreated diabetic rats. Liver glutathione levels of diabetic rats, which had received vitamin E (P < 0.01) and vitamin E + diltiazem (P < 0.05) had significantly increased when compared with untreated diabetic rats. Liver lipid peroxide levels had significantly decreased in diabetic rats, which had received vitamin E (P < 0.001) and diltiazem (P < 0.01). With respect to their metabolic and antioxidant effects, vitamin E proved superior to diltiazem.
Asunto(s)
Antioxidantes/farmacología , Bloqueadores de los Canales de Calcio/farmacología , Diabetes Mellitus Experimental/tratamiento farmacológico , Diltiazem/farmacología , Vitamina E/farmacología , Administración Oral , Animales , Antioxidantes/administración & dosificación , Glucemia/efectos de los fármacos , Bloqueadores de los Canales de Calcio/administración & dosificación , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/metabolismo , Diltiazem/efectos adversos , Modelos Animales de Enfermedad , Quimioterapia Combinada , Glutatión/metabolismo , Inyecciones Intraperitoneales , Hígado/efectos de los fármacos , Hígado/metabolismo , Ratas , Ratas Wistar , Estreptozocina , Vitamina E/efectos adversosRESUMEN
This study investigated the possible local adverse effects of intra-articular administration of tenoxicam in the rat knee joint. A total of 50 rats were given 0.25 ml of a standard preparation of tenoxicam by injection into the right knee joint and 0.25 ml of 0.9% saline solution by injection into the left knee joint as a control. Groups of 10 rats were killed 24 h, 48 h, 7 days, 14 days and 21 days after tenoxicam administration. Two rats were sham operated; one was killed on the first day and the other on the second day after this procedure. All the joints were prepared and sectioned for histological examination. Tissue loss and oedema were observed in the specimens obtained 24 h and 48 h after treatment with tenoxicam. No pathological changes were observed in the 7-day, 14-day and 21-day specimens, or in the control joints. Caution should be exercised when using intra-articular tenoxicam for post-operative analgesia.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Cartílago Articular/efectos de los fármacos , Piroxicam/análogos & derivados , Piroxicam/farmacología , Membrana Sinovial/efectos de los fármacos , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/efectos adversos , Cartílago Articular/patología , Inflamación/inducido químicamente , Articulación de la Rodilla/anatomía & histología , Articulación de la Rodilla/efectos de los fármacos , Articulación de la Rodilla/patología , Piroxicam/administración & dosificación , Piroxicam/efectos adversos , Ratas , Ratas Sprague-Dawley , Membrana Sinovial/patologíaRESUMEN
An increase in oxidative stress may contribute to the development of oxidative protein damage (OPD) in the streptozotocin-diabetic rat. To show the effect of hyperglycemia in promoting OPD, we determined protein carbonyl (PCO), nitrotyrosine (NT), total thiol (T-SH) and advanced oxidation protein product (AOPP) levels as markers of OPD, and lipid hydroperoxide (LHP) levels as a marker of lipid peroxidation in plasma of acute and chronic diabetic male Sprague-Dawley rats and their controls. The levels of the studied markers, except NT, were determined by colorimetric methods. NT levels were measured by ELISA. Plasma PCO and AOPP levels of chronic diabetic rats were increased significantly compared with those of both acute diabetic rats and the controls. Plasma NT levels of the three groups were not different. Plasma T-SH levels of acute diabetics were increased significantly compared with those of the controls while T-SH increase in the chronic diabetics was not significant. Plasma LHP levels were increased significantly in the chronic diabetic rats compared with those of the controls. The increase in plasma PCO, AOPP, LHP levels in chronic but not in acute diabetic rats may be indicating that persistence of hyperglycemia is involved in the evolution of OPD while plasma NT levels do not seem to reflect OPD in diabetes.
Asunto(s)
Diabetes Mellitus Experimental/sangre , Estrés Oxidativo , Proteínas/metabolismo , Tirosina/análogos & derivados , Animales , Biomarcadores , Diabetes Mellitus Experimental/metabolismo , Peróxidos Lipídicos/sangre , Masculino , Oxidación-Reducción , Proteínas/química , Ratas , Ratas Sprague-Dawley , Compuestos de Sulfhidrilo/sangre , Tirosina/sangreRESUMEN
Beneficial effects of medroxyprogesterone acetate (MPA) in cancer therapy is partly mediated via its antiangiogenic activity. The same is true for the antitumoral action of non-steroidal antiinflammatory drugs. We have studied two liposoluble drugs, MPA and the analgesic ibuprofen, on glioma vascularization in vivo. In this study we have shown that, until the sacrifice at 27. day after tumor inoculation in the right hemisphere, MPA had a slight though insignificant activity to reduce the fatality of C6 glioma, growing in right cerebral hemisphere of male Wistar rats. But ibuprofen both alone or with MPA had no effect on survival with gavage application of a 30 mg/kg/day dosing regime. On histological analysis, intra- and peritumoral vessels were counted. Progesterone seemed to lower intratumoral, but to increase peritumoral vessels, especially glomeruloids, around the tumor mass. Coadministration of ibuprofen acted to suppress the peritumoral vessel increase, and to enhance lymphomonocytic infiltration around tumor vessels.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Neoplasias Encefálicas/irrigación sanguínea , Glioma/irrigación sanguínea , Ibuprofeno/farmacología , Medroxiprogesterona/farmacología , Neovascularización Patológica/prevención & control , Congéneres de la Progesterona/farmacología , Animales , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/patología , Quimioterapia Combinada , Glioma/patología , Linfocitos/fisiología , Masculino , Neovascularización Patológica/mortalidad , Neovascularización Patológica/patología , Ratas , Ratas Wistar , Análisis de SupervivenciaRESUMEN
HYPOTHESIS: Tumor implantation (TI) development at the surgical wound following cancer surgery is still an unresolved concern. Trocar site recurrence, which is likely a form of TI, has become one of the most controversial topics and, with the widespread acceptance of laparoscopic surgery, has caused renewed interest in questions about TI. Honey has positive effects on wound healing. Physiological and chemical properties of honey might prevent TI when applied locally. DESIGN, INTERVENTIONS, AND MAIN OUTCOME MEASURES: Sixty BALB/c strain mice, divided into 2 groups, were wounded in the posterior neck area. Group 1 mice formed the control group, and group 2 mice had wounds coated with honey before and after tumor inoculation. All wounds were inoculated with transplantable Ehrlich ascites tumor. The presence of TI was confirmed in the wounded area by histopathological examination on the 10th day. RESULTS: Tumor implantation was achieved in all group 1 animals and verified by palpable mass and histopathological examination. In group 2 mice, although TI could not be detected macroscopically, it was revealed by pathological examination in 8 cases. Tumor implantation was less likely in group 2 mice (8 of 30 vs 30 of 30; P<.001). CONCLUSIONS: Tumor implantation was markedly decreased by the application of honey pre- and postoperatively. It is possible that the physiological and chemical properties of honey protected wounds against TI. Honey could be used as a wound barrier against TI during pneumoperitoneum in laparoscopic oncological surgery and in other fields of oncological surgery.
Asunto(s)
Miel , Siembra Neoplásica , Complicaciones Posoperatorias/prevención & control , Cicatrización de Heridas , Animales , Ratones , Ratones Endogámicos BALB C , Procedimientos Quirúrgicos Operativos/efectos adversosRESUMEN
Fetal tissue transplantation has gathered considerable interest among researchers dealing with organ transplantation. A large number of studies concerning fetal intestinal transplantation have been published in the past 2 decades, almost all of them aiming to determine the feasibility of a properly functioning fetal transplant in continuity with the host's own enteral system. This study was designed to determine the absorptive capacity of the neogut in vivo, without anastomosing the transplant to the host's intestine, and to evaluate its use as an accessory enteral segment. Intestinal segments taken from Wistar albino fetuses were transplanted subcutaneously into the abdominal wall of 20 Sprague-Dawley rats. Immunosuppression was maintained by daily cyclosporin A (Cy A) 10 mg/kg injections s.c. and evaluated by determination of serum Cy A level and T-helper/T-suppressor cell ratio. The neogut was converted into a Thiry-Vella loop 2 weeks after transplantation. A test solution composed of 20% glucose and Trophamine was perfused via the stomas; glucose and amino acid absorption gradients were calculated. The gamma-glutamyl transferase (GGT) activity and mitotic index of the neogut were determined. Results were compared to those obtained from the host. There was no significant difference (P > 0.05) in glucose absorption between the neogut and the host tissue. Amino acid absorption and specific GGT activity were significantly less (P < 0.01) in the neogut. There was no significant difference (P > 0.05) between neogut and host intestine in mitotic index. Our data support the idea of using a transplanted fetal intestinal segment as an accessory feeding route.
Asunto(s)
Trasplante de Tejido Fetal , Absorción Intestinal , Intestinos/trasplante , Aminoácidos/metabolismo , Animales , Trasplante de Tejido Fetal/patología , Terapia de Inmunosupresión , Mucosa Intestinal/metabolismo , Intestinos/patología , Índice Mitótico , Peptidil Transferasas/metabolismo , Ratas , Ratas Sprague-Dawley , Ratas Wistar , gamma-Glutamiltransferasa/metabolismoRESUMEN
Successful transplantation of encapsulated islets (bioartificial pancreas) would circumvent problems of islet availability and rejection in the treatment of insulin-dependent diabetes with biological organ replacement. Alginates are widely used as a hydrogel matrix or membrane for immunoprotected transplantation. A major problem in the use of diffusion-based devices is the biocompatibility of the material used. The foreign body reaction after implantation of empty microcapsules into different compartments in rats, dogs and pigs is evaluated in this article. However, biocompatibility of the bioartificial pancreas has three different aspects: reaction of the entrapped islet to the encapsulation technique and material; reaction of the recipient against the incorporated device ( = foreign body reaction); and finally the reaction of the recipient against the encapsulated islet ( = immunology of bioartificial pancreas). It is obvious from different experiments that even if foreign body reactions (reactions against material) are almost abolished the recipient may react against material released from the encapsulated islet. In conclusion, transplantation of encapsulated islets induces various morphological reactions (i.e. inflammation and fibrosis) as a result of a variety of donor and recipient related factors. Therefore, the use of an adequate animal model that reflects the human situation is essential for progress in the development of a bioartificial pancreas.
Asunto(s)
Materiales Biocompatibles/normas , Reacción a Cuerpo Extraño/prevención & control , Trasplante de Islotes Pancreáticos , Islotes Pancreáticos/inmunología , Alginatos/efectos adversos , Animales , Órganos Artificiales , Supervivencia Celular/inmunología , Diabetes Mellitus Tipo 1/terapia , Perros , Reacción a Cuerpo Extraño/inmunología , Humanos , Islotes Pancreáticos/citología , Islotes Pancreáticos/fisiología , Trasplante de Islotes Pancreáticos/inmunología , Microesferas , Ratas , PorcinosRESUMEN
The effects of calcium channel blockers (CCB)-verapamil, nifedipine, diltiazem on metabolic control in streptozotocin-induced long-term diabetes in rats were investigated. Diabetes mellitus was induced by single intravenous injection of streptozotocin (65 mg/kg body wt.). The animals were divided into five groups: a healthy control group, a diabetic group and three diabetic groups treated with one of the calcium channel blockers (verapamil, 25 mg/kg/day, nifedipine, 20 mg/kg/day, and diltiazem, 30 mg/kg/day, respectively). Body weight, glycemia, glycated hemoglobin and total serum protein levels of these animals were measured at the beginning and at the end (after 13 weeks) of the experiment. It was observed that diabetic animals who were not treated with CCB had lost weight at the end of the experiment (P < 0.01). The blood glucose and glycated hemoglobin levels were increased in the diabetic group in comparison to the healthy control group (P < 0.001). However, the calcium channel blockers seem to have beneficial effects on body weight, glycated hemoglobin and blood glucose levels.
Asunto(s)
Glucemia/metabolismo , Bloqueadores de los Canales de Calcio/farmacología , Diabetes Mellitus Experimental/sangre , Diltiazem/farmacología , Nifedipino/farmacología , Verapamilo/farmacología , Animales , Glucemia/efectos de los fármacos , Proteínas Sanguíneas/efectos de los fármacos , Proteínas Sanguíneas/metabolismo , Peso Corporal/efectos de los fármacos , Diabetes Mellitus Experimental/fisiopatología , Hemoglobina Glucada/efectos de los fármacos , Hemoglobina Glucada/metabolismo , Masculino , Ratas , Ratas Wistar , Valores de ReferenciaRESUMEN
The influence of selenium supplementation on the activity of Na(+)-K(+)-ATPase and on the degree of free radical generation was studied in brain tissue of rats. Selenium was administered for 5 months in drinking water, and was measured in plasma by the fluorometric method at the end of the experimental period. Animals were sacrificed and brain tissue homogenates were used for enzyme assay and for assessment of lipid peroxide formation. Brain tissue from rats who received selenium showed significantly increased Na(+)-K(+)- ATPase activity but also significantly decreased lipid peroxide farmation. Since this enzyme is known to be inhibited by oxygen free radicals, selenium supplementation appears to exert a beneficial effect on the Na(+)-K(+)-ATPase activity by preventing free radical-induced damage.
Asunto(s)
Encéfalo/enzimología , Selenio/farmacología , ATPasa Intercambiadora de Sodio-Potasio/efectos de los fármacos , Animales , Radicales Libres , Peroxidación de Lípido/efectos de los fármacos , Masculino , Microsomas/enzimología , Ratas , Ratas Sprague-Dawley , Selenio/sangreAsunto(s)
Absorción Intestinal , Intestino Delgado/trasplante , Aminoácidos/metabolismo , Animales , Relación CD4-CD8 , Ciclosporina/uso terapéutico , Glucosa/metabolismo , Rechazo de Injerto/inmunología , Rechazo de Injerto/patología , Íleon/patología , Íleon/fisiología , Íleon/trasplante , Intestino Delgado/patología , Intestino Delgado/fisiología , Yeyuno/patología , Yeyuno/fisiología , Yeyuno/trasplante , Índice Mitótico , Evaluación Nutricional , Ratas , Ratas Sprague-Dawley , Ratas Wistar , Valores de Referencia , Trasplante HomólogoRESUMEN
The aim of this study was to assess the relation between the use of cocaine during pregnancy and development of necrotizing enterocolitis in a rat model. Different doses of cocaine HCl were given to pregnant Wistar Albino rats during gestation. Total number of live births, mean birth weight, mean placental weight and histopathological examination of the maternal uterus, placenta, embryonal G-I tract and liver were investigated. These results were compared with a control group and showed that the number of live births, mean birth weight and mean placental weight were lower than in non-cocaine controls. Histopathologic examinations revealed severe inflammation and vascular changes in the uterus and placenta. We also observed focal necrosis, necrobiosis, cellular debris, haemorrhage, inflammatory reactions in the G-I tract of embryos. These findings indicate that maternal cocaine abuse should probably be considered a major risk factor for development of NEC in baby rats and embryos.