El pentosán polisulfato de sodio previene las alteraciones morfológicas renales y la albuminuria en ratas con diabetes tipo 1 / Pentosan polysulfate sodium prevents kidney morphological changes and albuminuria in rats with type 1 diabetes

Se ha reportado una disminución de los valores de glicosaminoglicanos (GAG) en el riñón y otros órganos en modelos experimentales de diabetes y en humanos. La administración a largo plazo de heparina y otros GAG previene las alteraciones morfológicas y funcionales del riñón en ratas diabéticas. Evaluamos el efecto del pentosán polisulfato de sodio (PPSNa), un mucopolis acárido semisintético similar a los GAG y de baja actividad anticoagulante, sobre la función renal y los cambios estructurales en ratas diabéticas. La diabetes fue inducida a ratas Sprague Dawley mediante la administración i.v. de estreptozotocina (STZ). Los animales fueron distribuidos al azar en tres grupos (C = control, STZ y STZ + PPSNa = pretratados con 15 mg/kg/día de PPSNa s.c.). Después de 3 meses se tomaron muestras de sangre y de orina de 24 horas; los animales fueron sacrificados y los riñones extraídos mediante microdisección para el análisis morfométrico. Los animales del grupo STZ presentaron un incremento importante de la excreción de albúmina en orina (C = 0,26 ±0,03 frente a STZ = 7,75 ± 1,8 mg/24 h), que fue parcialmente revertido por el pretratamiento con PPSN a (3,7 ± 0,7 mg/24 h),sin afectar al control metabólico, HbA1c(C = 3,6 ± 1,7; STZ = 8,82± 0,47; STZ + PPSNa = 8,63 ± 0,54). En las micrografías electrónicas se observan las lesiones renales típicas descritas en la diabetes experimental (grupo STZ). La administración de PPSNa previene el engrosamiento de la membrana basal tubular y la pérdida de la citoarquitectura inducida por la diabetes. Nuestros resultados demuestran que la administración de PPSNa previene parcialmente el daño renal en este modelo experimental y sugieren un potencial uso terapéutico de este compuesto (AU)

Decreased levels of glycosaminoglycans (GAG) have been observed in kidney and other organs, in human and animal models of diabetes. Long term administration of heparins and other glycosaminoglycans have demonstrated a beneficial effect on morphological and functional renal abnormalitiesin diabetic rats. We assessed the effect of sodium pentosen polysulfate (SPP), a semi-synthetic glycosaminoglycan with low anticoagulant activity, on renal involvement in streptozotocin diabetic rats. Diabetes was induced in male Sprague Dawley rats by i.v. administration of streptozotocin (STZ).Animals were randomly allocated in three groups: C = control, STZ and STZ + SPP = pretreated with SPP (15 mg/kg, s.c.).After three months of follow-up, blood and 24 h-urine samples were obtained and then the animals were sacrificed and the kidney microdissected for morphometric analysis. Urinaryalbumin excretion was markedly increased in untreated diabetic rats (C = 0.26 ± 0.03 vs. STZ = 7.75 ± 1.8 mg/24 h) andSPP treatment partially prevented the albumin rise (3.7 ± 0.7mg/24 h), without affecting the metabolic control HbA1c(C = 3.6 ± 1.7; STZ = 8.82 ± 0.47; STZ + SPP = 8.63 ± 0.54). Electron microscope observation revealed typical renal lesions described in experimental diabetes (STZ group). SPP administration prevent the tubular basement membrane thickening and the lost of cytoarchitecture induced by experimental diabetes. Our data demonstrated that long-term administration of SPP have a favorable effect on morphological and functional abnormalities in kidney of diabetic rats and suggests a potential therapeutic use for this compound (AU)

[Pentosan polysulfate sodium prevents kidney morphological changes and albuminuria in rats with type 1 diabetes]. / El pentosán polisulfato de sodio previene las alteraciones morfológicas renales y la albuminuria en ratas con diabetes tipo 1.

Decreased levels of glycosaminoglycans (GAGs) have been observed in the kidney and other organs, in human and animal models of diabetes. Long-term administration of heparins and other glycosaminoglycans has demonstrated a beneficial effect on morphological and functional kidney abnormalities in diabetic rats. We assessed the effect of pentosan polysulfate sodium (PPS), a semi-synthetic glycosaminoglycan with low anticoagulant activity, on kidney involvement in streptozotocin diabetic rats. Diabetes was induced in male Sprague-Dawley rats by i.v. administration of streptozotocin (STZ). Animals were randomly allocated to three groups: C = control, STZ and STZ + PPS = pretreated with PPS (15 mg/kg, s.c.). After three months of follow-up, blood and 24 h-urine samples were obtained, the animals were sacrificed and the kidney microdissected for morphometric analysis. Urinary albumin excretion was markedly increased in untreated diabetic rats (C = 0.26 ± 0.03 vs STZ = 7.75 ± 1.8 mg/24 h) and PPS treatment partially prevented the albumin rise (3.7 ± 0.7 mg/24 h), without affecting the metabolic control HbA1c (C = 3.6 ± 1.7; STZ = 8.82 ± 0.47; STZ + PPS = 8.63 ± 0.54). Electron microscope observation revealed typical renal lesions described in experimental diabetes (STZ group). PPS administration prevents the tubular basement membrane thickening and the loss of cytoarchitecture induced by experimental diabetes. Our data demonstrate that long-term administration of PPS has a favourable effect on morphological and functional abnormalities in kidneys of diabetic rats and suggests a potential therapeutic use for this compound.

Ultrastructural pathological changes in mice kidney caused by Plasmodium berghei infection.

Malaria, a common health problem in certain parts of the world, has a considerable morbidity and mortality. This work reports under electron microscopy studies serious ultrastructural kidney damage such as extensive cytoplasmic vacuolation, vesiculation and autophagic vacuoles in proximal tubular cells. A thickened endothelial wall on peritubular capillary, interdigitation disorganization and significant decrease of their number in some areas were detected. Swollen rough endoplasmic reticulum, swollen mitochondria, and parasitized erythrocytes were observed. Many epithelial cells exhibited cytoplasmic areas of autophagia and a myelin-like form. A tubular cell presented severe cytoarchitecture alterations. Abundant lipid droplets were noticed. Almost total loss of interdigitations, rough endoplasmic reticulum vesiculation, peritubular capillaries with endothelial cells thickened cytoplasm, papillary processes projected to the lumen, and an inflammatory infiltrate of macrophages were also observed. These ultrastructural kidney changes could cause, on the basis of their clinical and pathologic expressions, a fat accumulation, an acute temporary reversible glomerulonephritis, a chronic progressive irreversible glomerulonephritis, and an acute renal failure (ARF).

Effects of herbicide on the kidneys of two Venezuelan cultured fish: Caquetaia kraussii and Colossoma macropomum (Pisces:Ciclidae and Characeae)

The use of chemical pesticides and herbicides has increased environmental pollution and affected ichthyofauna in the watersheds where they are used.We studied the effect of an herbicide, triazine, on the kidneys of two species (Caquetaia kraussii and Colossoma macropomum )widely found in Caribbean and South American rivers.In Venezuela,these species are abundant and have a high aquaculture potential because they may be cultured and reproduced in captivity.Four kidney samples from juveniles of each species exposed to the herbicide were examined by Transmission Electron Microscopy.Kidney tubule alterations included loss of plasmalemma and cell interdigitations, misshaped mitochondria,decrease in rough endoplasmic reticulum and free polysomes,and the presence of autophagic vacuoles and primary lysosomes.These alterations at the cellular level may explain fish behaviour in terms of kidney tubule pathology,and relative amounts and conditions of organelles within affected cells

Effects of herbicide on the kidneys of two Venezuelan cultured fish: Caquetaia kraussii and Colossoma macropomum (Pisces: Ciclidae and Characeae).

The use of chemical pesticides and herbicides has increased environmental pollution and affected ichthyofauna in the watersheds where they are used. We studied the effect of an herbicide, triazine, on the kidneys of two species (Caquetaia kraussii and Colossomna macropomum) widely found in Caribbean and South American rivers. In Venezuela, these species are abundant and have a high aquaculture potential because they may be cultured and reproduced in captivity. Four kidney samples from juveniles of each species exposed to the herbicide were examined by Transmission Electron Microscopy. Kidney tubule alterations included loss of plasmalemma and cell interdigitations, misshaped mitochondria, decrease in rough endoplasmic reticulum and free polysomes, and the presence of autophagic vacuoles and primary lysosomes. These alterations at the cellular level may explain fish behaviour in terms of kidney tubule pathology, and relative amounts and conditions of organelles within affected cells.

Effects of Azadirachta indica and Melia azedarach (Meliaceae) extracts from leaves on Trypanosoma cruzi growth and ultrastructure.

The chloroformic extracts from dried fresh leaves ofAzadirachta indica A. Juss. and Melia azedarach L. (Meliaceae) showed marked inhibitory activity on epimastigotes growth of Trypanosoma cruzi, evidenced by 96-wells microtiter plate bioassay and radioactive thymidine incorporation experiment. Each chloroformic extract was separated using silica gel and alumina column. In transmission electron microscopy the bioactive chromatographic fractions caused ultrastructural changes in epimastigotes such as vacuolization probably induced by degeneration of the kinetoplast-mitochondrion complex, organelle degeneration, and cell division disruption. In spectral analysis these bioactive fractions seemed to be composed mainly of fatty acid mixtures.

Cellular and subcellular changes in muscle, neuromuscular junctions and nerves caused by bee (Apis mellifera) venom.

Biopsy specimens of cervico-scutular muscles obtained from animals injected with bee crude venom were prepared for electron microscopy studies. At 6 h from Apis mellifera venom injection, in mice under transmission electron microscopy, the muscular fibres presented different atrophy levels with increment of the intermyofibrillar spaces. Tubules and sarcoplasmic reticulum elements were altered, in some places only tubular fragments and an increment of the intermyofibrillar spaces were noticed as well as loss of fibre regularity and prominent triads. In subsarcolemma region, areas lacking myofibrils and mitochondria damages were observed. Muscular segmental necrosis and atrophy areas were observed. Neuromuscular junctions were altered. The number of synaptic vesicles was very variable and synaptic clefts showed irregularities. A decrease in the number and arrangement of the synaptic clefts, as well as free polysomes, suggesting regeneration processes, were also observed. The myelinic nerves exhibited in the axon or in the wall vacuolisation areas. The presence of severe muscular lesions, the finding of venom activities in the presynaptic region and the detection of damages in the neuromuscular junctions at different chronological stages of our experiments indicate that the bee venom is highly toxic for neuromuscular structures.

Inflammation and nitric oxide production in skeletal muscle of type 2 diabetic patients.

An inflammatory process may be involved in nitric oxide production in skeletal muscle of type 2 diabetic patients. Nitric oxide generation in skeletal muscle was assessed in 14 non-complicated type 2 diabetic patients and in 12 healthy subjects. In samples of quadriceps femoris muscle, endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), nitrite, nitrate and nitrotyrosine were determined. The macrophage-specific antigen CD163, the T-cell membrane factor CD154 and tumour necrosis factor-alpha (TNF-alpha) were also assayed. In six patients, ultrastructural analysis of muscle was performed. Nitrites and nitrates were increased in patients as compared to controls (22.7+/-4.5 and 32.7+/-7.0 vs 16.0+/-2.9 and 22.8+/-4.0 micromol/mg protein; P<0.001, Mann-Whitney U test). Endothelial NOS was similar in diabetic and control subjects (36.4+/-13.8 vs 36.3+/-6.8 ng/mg protein), contrasting with the significant increase of iNOS recorded in patients (34.3+/-13.0 vs 8.5+/-2.8 ng/mg protein, P<0.00002). Nitrotyrosine levels were higher in the patient than in the control group (42.1+/-24.4 vs 10.3+/-2.5 ng/mg protein, P<0.00002), as were CD163 (10-fold) and TNF-alpha (fourfold) levels. Furthermore, CD154 levels were detectable only in the patient samples (10.2+/-5.3 ng/mg protein). By multiple-regression analysis, changes in glycated haemoglobin values could predict 96% variation in nitrotyrosine. Macrophages were present in all muscle samples analysed by electromicroscopy. The increased levels of CD163, CD154 and TNF-alpha indicate that an inflammatory process occurs in skeletal muscle of type 2 diabetic patients. This may contribute to iNOS induction, muscle damage and insulin resistance.

Trypanosoma rangeli: ultrastructure and activity of the mitochondrion.

Axenic cultures of pure Trypanosoma rangeli were used to investigate the relation between ultrastructure and activity in the mitochondrion. Every other day, ultrathin sections were obtained from cultivated flagellates and, subsequently, observed in order to register changes in the cytoarchitecture of the organelle. Culture samples were incubated in tetrazolium salts to determine the mitochondrion's metabolic state. The results show a high correspondence between mitochondrion ultrastructural shape and function of the same organelle in populations of T. rangeli maintained under in vitro conditions.

Ultrastructural alterations in cortex of adrenal gland caused by the toxic effect of bee (Apis mellifera) venom.

Bee accidents incidence is underestimated because many people do not consult to the physicians. Here it is described for the first time the severe mice adrenal gland damage induced by Apis mellifera venom. Biopsy specimens were obtained from mice adrenal gland and after sample preparation observed in Hitachi H-7100 electron microscope. In this work the ultrastructural analysis showed, 6 h after injection, a non homogeneous smooth endothelial reticulum, and in some places loss of plasma membrane. The fenestrae spaces were bigger and detritus in the capillary lumen were observed. Erythrocytes were seen in a cortical cell. After 48 h of venom injection, expanded fenestrae were observed. Capillary basal membrane was interrupted. Myelin-like figures and autophagic vacuoles were noticed. Swollen smooth endoplasmic reticulum elements and endothelial unfolding to the light were seen. Moreover, swollen Golgi and mitochondria were observed, in some places forming myelinic-like figures. At 144 h after venom injection, widened spaces were noticed in capillary fenestrae. Cellular section showed swollen and lost smooth endoplasmic reticulum elements. Smooth endoplasmic reticulum tubules disappearance suggested non steroidogenesis. In conclusion, we suggest that some of the bee envenoming human clinical manifestations, as is observed in mice, are determined by suprarenal gland damage produced by toxins present in this venom.

Alteraciones estructurales v ultraestructurales del encéfalo ocasionados por veneno de la serpiente mapanare (Bothrops colombiensis) / Structural and ultrastructural encephalic alterations caused by the poison of the snake mapanare (Bothrops colombiensis)

Las actividades tóxicas y enzimáticas del veneno de serpiente mapanare (Bothrops colombiensis), cuya acción abarca casi todos los tejidos de mamíferos, no han sido estudiadas, estructural o ultraestructuralmente de manera exhaustiva, en el Sistema Nervioso Central (SNC).Se inocularon ratones adultos C57/Bl por vía endovenosa con concentraciones de veneno de 0,25 mg/kg de peso. Se sacrificaron a las 24 horas después de la inoculación de veneno y se hizo extracción del encéfalo, se fijó inmediatamente con paraformaldehído y se realizaron cortes vértico-tranversales, tomando áreas representativas de corteza cerebral y cerebelosa, asta de Amón, núcleos grises basales y tallo encefálico. Se prepararon para estudio de histología convencional (hematoxilina y eosina) y para microscopía electrónica, en un equipo de transmisión Hitachi HS-500. A1 extraer el encéfalo y hacer cortes coronales no se observaron lesiones macroscópicas, a pesar de verse intensa hemorragia en las áreas dérmicas. A la microscopía óptica, los cerebros de ratones mostraron eritrocitos extravasados en las leptomeninges y pericapilares, en los núcleos grises centrales, así como ligera espongiosis subpial, pericapilar y en el neuropilo. En el ámbito ultrastructural, las células endoteliales de los capilares corticales se encontraban tumefactas con algunas vesículas de pinocitosis en la superficie luminal, la luz capilar ocluida y mitocondrias hinchadas. Además se observó tumefacción de las prolongaciones astrogliales pericapilares. El endotelio de los capilares de los plexos coroideos mostró algunas figuras mielínicas citoplasmáticas y engrosamiento de la membrana basal.En conclusión, la actividad del veneno de Bothrops colombiensis no fue de la intensidad que se observa en otros tejidos del organismo, probablemente por el efecto protector de la barrera hematoencefálica, que pudiera bloquear la acción de muchos componentes tóxicos y enzimáticos del veneno. Este hecho es observado en pacientes humanos mordidos por serpientes de esta especie, donde los hallazgos de daño del SNC son escasos (AU)

Estudio clinico, histopatológico y ultraestructural del músculo de la lengua en pacientes con carcinoma epidermoide / A clinical, histopathological and ultrastructural study of tongue muscle in patients with squamous cell carcinoma

En el presente trabajo se realizó un estudio mediante microscopÝa de luz y electrónica de transmisión con el fin de estudiar las alteraciones musculares producidas en el músculo de la lengua en pacientes con carcinoma epidermoide. Las anomalÝas estructuras observadas incluyeron, alteraciones tanto en el sistema contrßctil como sarcotubular, por otro lado se observó atrofia y necrosis segmentaria, alteración de mitocondrias y proliferación de organelos, asÝ como vaculolas, lisosomas y grßnulos de lipofucsina. El infiltrado mononuclear estuvo representado principalmente por neutrófilos, macrófagos y mastocitos. Este estudio representa el primer reporte sobre las alteraciones ultraestructurales a nivel del músculo de la lengua producida por esta patologÝa maligna

Kidney structural and ultrastructural pathological changes induced by uracoan rattlesnake (Crotalus vegrandis Klauber 1941) venom.

Acute renal insufficiency related to acute tubular necrosis is the most important complication caused by crotalid bite. For structural and ultrastructural studies of renal tissue, mice injected with crude venom or C. vegrandis haemorrhagic fraction, and controls were tested. Light microscopy analysis of kidneys at 24 h after injection of crude venom showed only moderate alterations such as tubular epithelia microvacuolisation. After 120 h marked glomerular and tubular capillaries congestion and interstitial oedema were observed. At 24 h after Uracoina-1 i.p. injection, intense glomerular and peritubular capillaries congestion was observed. Electron microscopic analysis of kidneys 24 h after i.p. injection of crude venom showed, capillary endothelial cell debris and pleomorphic mitochondria. Loss of interdigitations regularity, abundant dense bodies and light widening of the basal membrane were observed. Autophagic vacuoles were present as well as endothelia unfolding to the lumen and altered forms of podocytes. At 48 h, augmented endothelia without fenestrae formation with sequestration of low optical density debris inside the protrusions were noticed. At 120 h, capillary residues with loss of the endothelium were present and the basal membrane was widened. At 15 days, the number of vesicles and vacuoles in the tubules was increased and only few interdigitations were noticed. Autophagic vacuoles and mitochondrial matrix low electron density were observed. At 120 h after injection of crude venom, vascular damage with loss of capillary cell structures and collagen fibres were observed. At 24 h of haemorrhagic fraction injection, presence of autophagic vacuoles and myelinic figures were noticed.

Skeletal muscle ultrastructural pathology in mice infected with Trypanosoma evansi.

An ultrastructural study of skeletal muscle alterations wascarried out in mice experimentally infected with Trypanosoma evansi. Manifested anomalies were found, in both muscle fibre and microvasculature. Muscle fibre changes included atrophy, autophagic vacuoles formation, mitochondrial degeneration, nuclei pyknosis and segmental necrosis. In another direction, the cytoplasm of capillary endothelial cells showed rough endoplasmic reticulum and mitochondrial swelling, as well as luminal infoldings; parasites were found in the endothelial cell cytoplasm. A mononuclear infiltrate, formed by macrophages and neutrophils, was also observed. This work shows that skeletal muscle is an important target tissue for Trypanosoma evansi.

Extraocular muscle ultrastructural pathology in the paraneoplastic phenomenon associated with retinoblastoma.

Extraocular muscle biopsies were obtained during enucleation because of advanced intraocular retinoblastoma in four patients admitted to the Service of Ophthalmology at the Caracas University Hospital. Slight limitations of ocular movements and strabismus were present in all cases. The electron microscopical analysis showed muscle fibres with slight to severe atrophy exhibiting myopathic structures as nemaline, filamentous and zebra bodies. Fibre necrosis was also observed characterized by sarcomeric hypercontraction, autophagia, sarcolemmal disruption, and mitochondrial swelling. Capillary alterations included endothelial proliferation with intraluminal infoldings and, in some cases, capillary degeneration and necrosis. A mononuclear cell infiltration formed by macrophages and scarce mast cells located next to atrophic fibres and altered capillaries was observed. Additionally, neutrophils were found around capillaries and in their wall. Cancer cells invading muscle tissue were not seen. Two different ethiopathogenic mechanisms for muscle damages seem to be present. Because of the similarity between the microvascular changes we observed and those found in the muscle compromise of several autoimmune diseases, an autoimmune component in the ethiopathogenesis of the observed capillary alterations is proposed. On the other hand, abnormalities observed in muscle fibres are very similar to those in neurogenic atrophy. This study represents the first report on an extraocular muscle paraneoplastic phenomenon associated with orbital tumours.

Skeletal muscle microvascular alterations in euthyroid and hypothyroid patients with autoimmune thyroid disease.

An electron microscopic study of skeletal muscle biopsies from euthyroid and hypothyroid patients with autoimmune thyroid disease (ATD) showed the existence of capillary alterations and a mononuclear cell infiltrate. Microvascular abnormalities included thickening and lamination of basement membrane, endothelial proliferation with progressive lumen occlusion, and hypertrophied pericytes. Capillary degeneration was also observed. Macrophages, and scarce lymphocytes and mast cells formed the cell infiltrate. This pathological picture is similar to that found in the muscular compromise of other autoimmune diseases, particularly Graves' hyperthyroidism. This study shows that patients with ATD may have skeletal muscle capillary abnormalities that could probably be related to autoimmunity and are independent of thyroid functional status.

Salivary gland ultrastructural alterations in mice inoculated with Tityus discrepans (Buthidae) venom.

In this work we have studied the possible relationships between clinical manifestations such as sialorrhea, appearing in response to the toxic aggression by Tityus discrepans venom, and the alterations or changes at cellular or subcellular levels in sub-maxillary salivary glands in the murine model. To evaluate salivary gland subcellular response to Tityus discrepans venom, male C57/Bl adult mice were randomised into two groups: a group of mice were intraperitoneally injected with Tityus discrepans venom at a dose of 5 mg/Kg of weight and controls received saline solution. In the salivary glands from the envenomed animals sub-cellular changes such as hyperchromatic nucleus, swollen rough endoplasmic reticulum, granules of different electron density, some of them practically transparent, nucleolus of low density and big size and electron-transparent cisterns were observed. Capillary wall was augmented in certain areas and thin in others. Endothelial cell infolding to the lumen was seen. The distribution of the vesicles and its density varied. Macrophages and plasmocytes were observed next to the damaged capillaries. Different electron density of cytoplasm was noticed. In conclusion, we suggest that sialorrhea is determined by salivary gland damage produced by toxins present in this venom.

Hepatocyte ultrastructural alterations in cocaine users.

The ultrastructural examination of liver biopsies from five male cocaine users showed hepatocytes presenting diverse alterations in rough and smooth endoplasmic reticulum, mitochondria, nuclei and microvilli. Lipid deposition and an increase of autophagic vacuoles were also observed. This study demonstrates that the hepatocyte is an important target cell for cocaine toxic effects in some patients.

Capillary changes in skeletal muscle of patients with essential hypertension.

Arterial hypertension produces changes along the vascular tree. However, there are few reports on its effect on human muscle capillaries. This study demonstrates the effects of essential hypertension on the capillaries of human quadriceps muscle. Muscle biopsy was taken from quadriceps femoris in eight men with recent diagnosis of essential hypertension, without treatment. Biopsies were also taken from eight normotensive men and were used as controls. Fiber types were classified by ATPase reaction, capillaries counted in alpha-amylase-PAS stained sections and ultrastructure studied by conventional methods of transmission electron microscopy. No changes were found in capillaries or muscle fiber types by histochemical methods. However, electron microscopy revealed abnormal capillaries with endothelial cells infoldings into the lumen, as well as occluded or degenerated capillaries. In some cases the endothelial cell area covered by pericytes was increased. Basement membrane of capillaries was frequently increased in width, sometimes irregularly, and in other instances it was reduplicated. In transversely sectioned capillaries lumen diameter was reduced and wall thickness was increased, although total diameter was unchanged. In hypertensive patients the finding of some degenerated capillaries adjacent to muscle fibers could be interpreted as the beginning of a process of rarefaction. Some capillaries showed morphological changes, and the ratio wall thickness/lumen was increased.

Liver ultrastructural pathology in mice envenomed with Uracoan rattlesnake (Crotalus vegrandis) venom.

In South America rattlesnake venom activities have not been entirely characterised. Some studies have shown haemorrhagic, myotoxic, and neurotoxic effects as manifestations of envenoming in experimental animals and humans. Biopsy specimens were obtained from liver and immediately fixed in situ and observed in Hitachi H-500 and H-7100 electron microscopes. In this work the ultrastructural analysis of experimental mice liver showed hepatocytes with increased lipid droplets content and significant vacuolation in areas of their cytoplasm limiting with the Disse space. Lysosomes and altered peroxisomes exhibiting a very dense electron content were also evident. Mitochondrial pleomorphism including cup-shaped and ring-shaped mitochondria were frequently found. The cristae were scarce or absent in the majority of mitochondria observed. The rough endoplasmic reticulum showed a preferentially disposition lining the outer mitochondrial membranes. In some section glycogen particles were scarce and lipofuchsin granules could be observed. Red blood cells showed endothelial cell adherence and, in many instances, the liver sinusoids were observed plugged with aggregated red blood cells. In conclusion, using an animal model that probably correlates well with the pathological effects found in envenomed humans, we have shown the severe hepatocellular alterations caused by this venom.