Safety profile of colocasia esculenta tuber extracts in benign prostate hyperplasia.

INTRODUCTION: This study was motivated by the increasing global incidence of benign prostatic hyperplasia (BPH) and the promising potential of nutraceuticals as complementary therapies in ameliorating its burden. We report the safety profile of C. esculenta tuber extracts, a novel nutraceutical in benign prostate hyperplasia in a rat model. METHODS: In this study, forty-five male albino rats were randomly assigned to 9 groups of 5 rats each. Group 1 (normal control) received olive oil and normal saline. Group 2 (BPH untreated group) received 3 mg/kg of testosterone propionate (TP) and normal saline, and group 3 (positive control) received 3 mg/kg of TP and 5 mg/kg of finasteride. Treatment groups 4, 5, 6, 7, 8, and 9 received 3 mg/kg of TP and a middle dose (200 mg/kg) of LD50 of ethanol crude tuber extract of C. esculenta (ECTECE) or hexane, dichloromethane, butanone, ethyl acetate and aqueous fractions of ECTECE respectively for a period of 28 days. RESULTS: The negative controls showed a significant (p < 0.05) increase in mean relative prostate weight (approximately 5 times) as well as a reduction in relative testes weight (approximately 1.4 times less). There was no significant (p > 0.05) difference in the mean relative weights of most vital organs: liver, kidneys, and heart. This was also observed in hematological parameters: RBC, hemoglobin, HCT, MCV, MCH, MCHC, and platelets counts. In general, we note that the effects of the well-established drug finasteride on the biochemical parameters and histology of selected organs are comparable to those of C. esculenta fractions. CONCLUSION: This study demonstrates that C. esculenta tuber extracts provide potentially safe nutraceutical if applied in the management of benign prostate hyperplasia based on a rat model.

Comparative in vivo antimalarial activities of aqueous and methanol extracts of MAMA powder - A herbal antimalarial preparation.

ETHNOPHARMACOLOGICAL RELEVANCE: The choice of extraction solvent is a significant consideration in ethnomedicine as optimal extraction could influence the bioactivity of the herbal medicinal product. AIM OF STUDY: This study investigated the possible influence of the choice of solvents (methanol and water) for extracting MAMA Powder (MP) against Plasmodium berghei-infected mice to optimize its antimalarial activity and for developing other pharmaceutical dosage forms. MATERIALS AND METHODS: Aqueous and methanol extracts of MP, obtained through the decoction and soxhlet methods, respectively, were subjected to liquid chromatography-mass spectroscopy (LC-MS) for their respective fingerprints. The antimalarial activities of the methanol and aqueous extracts (12.5-100 mg/kg) were evaluated orally using the chemosuppressive test model on chloroquine-sensitive Plasmodium berghei-infected mice. The methanol extract was subjected to the established infection and prophylactic antimalarial tests with chloroquine (10 mg/kg) and pyrimethamine (1.25 mg/kg) as positive controls, respectively. The aqueous extract was investigated in chloroquine-resistant P. berghei using the chemosuppressive (12.5-800 mg/kg) and established infection (25-400 mg/kg) antimalarial models. RESULTS: The LC-MS fingerprints of both aqueous and methanol extracts revealed similar indole alkaloid contents. Chemosuppressive activity of the aqueous extract (75.3%) was significantly (p < 0.05) higher than the methanol extract (67.6%). In the chloroquine-resistant P. berghei infection experiments, the aqueous extract (400 mg/kg) exhibited significant parasite clearance (72%). CONCLUSION: The study concluded that the water extract with higher antimalarial activity could be optimized for chloroquine-resistant malaria and can thus facilitate the production of liquid and solid dosage forms.

Corrigendum to "Long-term consumption of virgin coconut (Cocos nucifera) oil diet impairs learning and memory in CD1 mice" [Chinese Herbal Medicines 12 (2020) 414-420].

[This corrects the article DOI: 10.1016/j.chmed.2020.03.008.].

Corrigendum to “Long-term consumption of virgin coconut (Cocos nucifera) oil diet impairs learning and memory in CD1 mice” Chinese Herbal Medicines 12 (2020) 414–420 (Chinese Herbal Medicines (2020) 12(4) (414–420), (S1674638420300770), (10.1016/j.chmed.2020.03.008)) / 中草药·英文版

When this paper was first published the following ethical statement was omitted in error: All animal experiments followed the guidelines established by the Institutional Animal Ethical Committee of University of Calabar, Nigeria. The authors would like to apologise for any inconvenience caused.

Modulation of Oxidative Stress and Inflammatory Cytokines as Therapeutic Mechanisms of Ocimum americanum L Extract in Carbon Tetrachloride and Acetaminophen-Induced Toxicity in Rats.

Liver diseases have now become a global canker due to increasing drug abuse and several viral infections. The current medicines on the market are woefully inadequate and limited in the application against these diseases. Fortunately, medicinal plants continue to serve as a potential source of drug discovery that could be explored to improve the situation. The present study, therefore, evaluated the hepatoprotective activities of the aqueous extract of various parts (leaves, flower and stem) of Ocimum americanum L on carbon tetrachloride (CCl4)- and acetaminophen-induced toxicity in rats. The protective effect of the plant was assessed using biochemical parameters, histology, levels of liver antioxidants, and expression of some pro-inflammatory cytokines (NF-κß and IL-1) in the liver. The leaves and stem extracts, orally administered for 7 days at 250 mg/kg, effectively prevented CCl4-induced elevation of serum biochemical parameters, prooxidants, as well as the expression of NFk-B and IL-1, which were comparable to Silymarin (standard drug). A comparative histopathological analyses of the liver exhibited virtually normal architecture compared with CCl4-treated group. The findings showed that the hepatoprotective effect of Ocimum americanum was probably due to the inhibition of oxidative stress and downregulation of proinflammatory cytokines by the effective parts of the medicinal plant.

Smilax china leaf extracts suppress pro-inflammatory adhesion response in human umbilical vein endothelial cells and proliferation of HeLa cells.

Objective: The objective of this study was to investigate the anti-inflammatory and anticancer effects of the leaves of Smilax china.Methodology: The aqueous extract was examined for its anti-inflammatory effects on tumour necrosis factor (TNF)-α-induced inflammation in HUVECs whereas the aqueous (water), ethyl acetate (EA), butanol (B) and methylene chloride (MC) extracts were examined for their anticancer effect on HeLa cells.Results: The aqueous extract suppressed the (TNF)-α-induced expression of ICAM-1, VCAM-1 and TNF-R1 and attenuated the expression of MCP-1, MMP-9, NF-kB and IFN-γ. The MC extract suppressed the proliferation of HeLa cells at all doses employed (50, 150, and 300 µg/ml). The EA extract demonstrated appreciable anti-proliferative effect whereas the BuOH extract demonstrated mild anti-proliferative activity. The aqueous extract did not show any significant anti-proliferative effect. None of the extracts were toxic to the normal cells (HUVECs).Conclusion: Smilax china leaf extracts possess significant anti-inflammatory and anticancer effects.

Effect of fatty acids from ethanol extract of Moringa oleifera seeds on kidney function impairment and oxidative stress induced by gentamicin in rats.

Gentamicin, an aminoglycoside drug, used for the treatment of Gram-negative bacterial infections. Despite its potency against bacterial infections, its clinical use is limited owing to nephrotoxicity effect. However, the study investigated the nephroprotective effect of fatty acids from ethanolic extract of Moringa oleifera seeds (EEMOS) against gentamicin-induced kidney injury in rats. Forty-five male Wistar rats, 100-160 g, were divided into 5 groups as follows: Group 1 (control), 5 rats, received 0.2 ml/100 g/day of propylene glycol orally for 28 days. Group 2, 10 rats, received 100 mg/kg/day (i.p) of gentamicin (GENT) for 8 days. Group 3-5, 10 rats each, treated with EEMOS orally for 28 days at graded doses of 100, 200 and 400 mg/kg respectively after GENT treatment. Twenty four after treatment, five rats from each group were sacrificed. The remaining 5 rats were sacrificed after 2 weeks recovery period from the drugs. The result showed that GENT elicited polyuria, elevated plasma creatinine, urea, and lower plasma electrolytes and creatinine clearance levels. Measurements of 24 h urinary output demonstrated marked decrease in creatinine and potassium levels in the GENT-treated group, whereas sodium level remain unchanged. Also, GENT caused significant decrease in superoxide dismutase and an increase in malondialdehyde levels in the kidney of the rats. Histopathological examination revealed evidence of necrosis of the kidney. Treatment with EEMOS significantly ameliorated the alterations caused by GENT in the plasma, urine and kidney homogenate of the rats. Hence, the mono- and poly-unsaturated fatty acids present in EEMOS were responsible for its renoprotective ability.

Potential of Three Ethnomedicinal Plants as Antisickling Agents.

Sickle cell disease (SCD) is a genetic blood disorder that affects the shape and transportation of red blood cells (RBCs) in blood vessels, leading to various clinical complications. Many drugs that are available for treating the disease are insufficiently effective, toxic, or too expensive. Therefore, there is a pressing need for safe, effective, and inexpensive therapeutic agents from indigenous plants used in ethnomedicines. The potential of aqueous extracts of Cajanus cajan leaf and seed, Zanthoxylum zanthoxyloides leaf, and Carica papaya leaf in sickle cell disease management was investigated in vitro using freshly prepared 2% sodium metabisulfite for sickling induction. The results indicated that the percentage of sickled cells, which was initially 91.6% in the control, was reduced to 29.3%, 41.7%, 32.8%, 38.2%, 47.6%, in the presence of hydroxyurea, C. cajan seed, C. cajan leaf, Z. zanthoxyloides leaf, and C. papaya leaf extracts, respectively, where the rate of polymerization inhibition was 6.5, 5.9, 8.0, 6.6, and 6.0 (×10-2) accordingly. It was also found that the RBC resistance to hemolysis was increased in the presence of the tested agents as indicated by the reduction of the percentage of hemolyzed cells from 100% to 0%. The phytochemical screening results indicated the presence of important phytochemicals including tannins, saponins, alkaloids, flavonoids, and glycosides in all the plant extracts. Finally, gas chromatography-mass spectrometry analysis showed the presence of important secondary metabolites in the plants. These results suggest that the plant extracts have some potential to be used as alternative antisickling therapy to hydroxyurea in SCD management.

In-vitro anticancer activity of green synthesized silver nanoparticles on MCF-7 human breast cancer cells.

In recent years, green synthesis of metallic nanoparticles is a growing area of research because of their potential applications in nanomedicine. In the present study we synthesized silver nanoparticles (silver NPs) from AgNO3 using aqueous extract of Lonicera hypoglauca flower as reducing and capping agents. The synthesized silver NPs were characterized using UV-Vis spectroscopy, FTIR, SEM-ED, TEM and SAED. Silver NPs were found to be significantly toxic to MCF-7 cells via the induction of apoptosis whereas sparing normal immune system (RAW 264.7) cells.

Antisickling and toxicological evaluation of the leaves of Scoparia dulcis Linn (Scrophulariaceae).

BACKGROUND: Scoparia dulcis Linn (Scrophulariaceae) together with other medicinal plants serve as antisickling remedies in Africa. This study was aimed at investigating the antisickling activity of the leaves of the plant as well as establishing the toxicological profile. METHOD: Chemical tests were employed in phytochemical investigations. Evaluation of the antisickling activity involved the inhibition of sodium metabisulphite-induced sickling of the HbSS red blood cells obtained from confirmed sickle cell patients who were not in crises. Concentrations of the crude extract and its fractions were tested with normal saline and p-hydroxybenzoic acid serving as controls. Acute toxicological evaluation was carried out in mice while 30-day assessment was done in rats. RESULTS: Phytochemical screening revealed the presence of alkaloids, tannins, flavonoids and saponins. Percentage sickling inhibitions of the aqueous methanol extracts of S. dulcis were significant all through the period of assay p < 0. 05 compared to normal saline, but not significant with PHBA. The fractions had less activity compared to the crude extracts. The LD 50 of the extract in mice was above 8000 mg/kg body weight when administered orally. Toxicological evaluations at 250 and 500 mg/kg showed mild congestion in virtually all the target organs. CONCLUSION: The antisickling results confirmed traditional usage of Scoparia dulcis in the management of Sickle cell disorders and a candidate for further investigations.

Studies of the antitrypanosomal and toxicological properties of Anogeissus leiocarpus (Dc.) Guill. & Perr. (Combretaceae) and Vitellaria paradoxa C. F. Gaertn (Sapotaceae) in mice / Estudios de las propiedades antitripanosómicas y toxicológicas de Anogeissus leiocarpus (Dc). Guill. & Perr. (Combretaceae) y Vitellaria paradoxa C. F. Gaertn (Sapotaceae) en ratones

African animal trypanosomosis (AAT) is a disease of concern with ravaging effects on the health of both animals and livestock in tropical Africa. This study investigates the anti-trypanosomal activities of Anogeissus leiocarpus (ALE) and Vitelleria paradoxa (VPE) stem bark extracts and also determines the toxicological profile of the active plant, with a view to establishing the anti-trypanosomal potential and safety of the plants. Laboratory mice (19 g – 26 g) and rats (140 g – 165 g) obtained from the Animal house, Faculty of Pharmacy, OAU, Ile-Ife were used for the study. The animals were treated according to the standard set criteria for animal use and care. VPE showed neither trypanocidal nor trypanostatic activities while ALE was found to be trypanostatic at 62.5 and 125 mg/kg body weight. However, the partitioned aqueous fraction of ALE was found to demonstrate comparable anti-trypanocidal effect as Diminal (standard agent). In conclusion, the ethanolic extract of A. leiocarpus possesses antitrypanosomal effect through the relative suppression or delay in parasite establishment in trypanosome-infected mice. The toxicological study of A. leiocarpus stem bark extract revealed that it is relatively safe for use in cattle and other grazing animals.

La tripanosomiasis africana de los animales es una enfermedad de preocupación que causa estragos sobre la salud de los animales y el ganado en África tropical. Este estudio investiga las actividades anti-tripanosomal de Anogeissus leiocarpus (ALE) y Vitelleria paradoxa (VPE) del tallo y extractos de corteza. También determina el perfil toxicológico de la planta activa, con el fin de establecer el potencial anti-tripanosomal y la seguridad de las plantas. Ratones de laboratorio (19 g - 26 g) y ratas (140 g - 165 g) obtenidos del Bioterio de la Facultad de Farmacia de la OUA, se utilizaron para el estudio. Los animales fueron tratados de acuerdo con los criterios estándar establecido para el uso y cuidado de animales. VPE mostró actividades no tripanocidas ni tripanostáticas mientras que en ALE se encontró que era tripanostático a 62,5 y 125 mg/kg de peso corporal. Sin embargo, se encontró que la fracción acuosa de ALE demostró un efecto anti-tripanocida comparable como Diminal (agente estándar). En conclusión, el extracto etanólico de A. leiocarpus posee efecto sobre tripanosomas a través de la supresión relativa o retraso en la creación de parásitos en ratones infectados con tripanosomosis. El estudio toxicológico del extracto de corteza del tallo A. leiocarpus reveló que es relativamente seguro para su uso en el ganado y otros animales de pastoreo.

Chemotherapeutic interaction between Khaya grandifoliola (WELW) CDC stem bark extract and two anti-malarial drugs in mice.

In malarial endemic countries especially in the tropics, conventional antimalarial drugs are used with herbal remedies either concurrently or successively. Khaya grandifoliola is one of such popular herbs used in the treatment of malaria.Various doses of ethanol extract of K. grandifoliola stem bark (50-400 mg/kg/day) were administered orally to Swiss albino mice infected with Plasmodium yoelii nigerense. A dose of 100 mg/kg/day of the extract was also combined with 2.5 mg/kg/day of chloroquine or 6.25 mg/kg/day of halofantrine in both early and established malaria infection test models. The results showed that in the early malaria infection test, K. grandifoliola in combination with chloroquine or halofantrine elicited enhanced antiplasmodial effect in the established infection, there was significantly greater parasite clearance following administration of the combination when compared to the effects of K. grandifoliola or the conventional drugs alone. The mean survival period of parasitized animals was also enhanced by the extract/halofantrine combination. Lower therapeutic doses of halofantrine may be required to potentiate parasite clearance when used in combination with K. grandifoliola. This may constitute great advantage to halofantrine which is associated with cardiotoxicity at high doses.

Viscum album (mistletoe) extract prevents changes in levels of red blood cells, PCV, Hb, serum proteins and ESR in high salt-fed rats.

AIM OF THE STUDY: The present study was aimed to determine the effects of Viscum album (mistletoe) on red blood cells, packed cell volume, Hb content, absolute haematological values {mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), colour index (CI)}, plasma proteins and ESR in high salt-fed rats. MATERIALS AND METHODS: 24 male albino Wistar rats were divided into 4 groups of 6 rats each. Group 1 received normal rat pellets+drinking water. Group 2 took same as group 1+mistletoe extract (150 mg/kg body weight, orally once daily). Group 3 took high salt (8% NaCl) diet+1% NaCl drinking water. Group 4 took same as group 3+mistletoe extract (150 mg/kg body weight, orally once daily). The feeding regimens lasted for 6 weeks. RESULTS: We observed that the mean RBC, PCV and Hb in the control group were 5.21+/-0.09 x 10(6)cells/mm(3), 43.50+/-1.61%, and 10.88+/-0.21 g/dl respectively. The extract significantly (P<0.05) reduced the RBC (5.72+/-0.08 x 10(6)cells/mm(3)), PCV (54.50+/-2.64%) and Hb (14.33+/-5.78 g/dl) in high salt-fed rats to near control levels. The extract also brought the elevated total plasma protein levels and reduced ESR in the high salt-fed rats (86.77+/-1.08 g/L and 1.83+/-0.31 mm/h respectively) to near control levels (82.23+/-0.91 g/L and 2.83+/-0.31 mm/h respectively), indicating the ability of the extract to prevent marked changes in the blood viscosity. The MCV, MCH, MCHC, and CI were not significantly altered by either extract or salt loading. CONCLUSION: Crude mistletoe extract prevents changes in RBC, PCV, plasma protein levels, and ESR, and indication that the extract prevents changes in blood viscosity a major determinant of arterial blood pressure.

Effect of ethanolic extract of Dennettia tripetala fruit on haematological parameters in albino Wistar rats.

The effect of oral administration of ethanolic extract of Dennettia tripetala fruits on haematological parameters in albino Wistar rats was investigated. Lethality studies revealed that the extract had an LD50 value of 251.19mg/kg mice intraperitoneal. Fifteen (15) male albino wistar rats weighing between 150 - 200g were used for the study and randomly assigned into three study groups of five animals each. The group 1 control received via oral route a placebo (4ml of normal saline), while test groups 2 and 3 received 85mg/kg body weight and 170mg/kg body weight of D. tripetala extract in 2.0ml and 4.0ml of the vehicle (normal saline) via oral route respectively. The administration of ethanolic extract of D. tripetala for 14 days produced a significant (P < 0.05) decrease in RBC and WBC counts in group 2 versus group 1 (control) but the decrease in RBC and WBC counts in group 3 were not significant compared to group 1. There was no significant difference in PCV and haemoglobin levels in groups 2 and 3 compared to control. The differential WBC results showed a significant increase (P < 0.001) in neutrophil count in group 2 versus group 1. While neutrophil count in group 3 was significantly decreased (P <0.001) compared to group 1. There was a significant decrease (P < 0.01) in eosinophil count in groups 2 and 3 when compared to the control group. From the results, there was a significant decrease (P < 0.001) in lymphocyte count in group 2 while a significant increase (P <0.01) in lymphocyte count was observed in group 3 when compared to the control group. There were no significant differences in basophils and monocytes counts in groups 2 and 3 compared to the control group. The study shows that D. tripetala extract, given at moderate to high doses may have hematotoxic effect, but the effect was worse with moderate doses.

Anti-inflammatory and hypoglycaemic effects of Tetrapleura tetraptera (Taub) [Fabaceae] fruit aqueous extract in rats.

The fruit of Tetrapleura tetraptera (Taub) [Fabaceae] is frequently used in Tropical African traditional medicine for the management and/or control of an array of human ailments, including arthritis and other inflammatory conditions, asthma, diabetes mellitus, hypertension, epilepsy, schistosomiasis, and so on. The present study was undertaken to examine the anti-inflammatory and hypoglycaemic effects of Tetrapleura tetraptera (Taub) fruit aqueous extract in rats. Fresh egg albumin-induced pedal oedema and streptozotocin (STZ)-induced diabetes mellitus were used as experimental test models of inflammation and diabetes. Diclofenac (DIC, 100mg/kg p.o.) and chlorpropamide (250 mg/kg p.o.) were employed as reference anti-inflammatory and hypoglycaemic agents, respectively, for comparison. Tetrapleura tetraptera (TTE, 50-800 mg/kg p.o.) produced dose-related, significant reductions (P < 0.05-0.001) of the fresh egg albumin-induced acute inflammation of the rat hind paw oedema. The plant extract (TTE, 50-800 mg/kg p.o.) also produced dose-dependent, significant reductions (P < 0.05-0.001) in the blood glucose concentrations of both fasted normal and fasted diabetic rats. The results of this experimental animal study indicate that T. tetraptera fruit aqueous extract possesses anti-inflammatory and hypoglycaemic properties. These findings lend pharmacological credence to the suggested folkloric uses of the plant's fruit in the management and/or control of arthritis and other inflammatory conditions, as well as in adult-onset, type-2 diabetes mellitus in some Yoruba-speaking communities of South-Western Nigeria.

Analysis of the distribution of MRI contrast agents in the livers of small animals by means of complementary microscopies.

BACKGROUND: Magnetic resonance imaging (MRI) contrast agents contain magnetic molecules such as iron (Fe) or gadolinium (Gd) that are injected in vivo into rats or mice to study their distribution inside the liver. Fluorescent europium (Eu) can be used as a model of Gd to obtain comparable information of this distribution of corresponding contrast agents. In a similar approach, Fe can be attached to Texas Red and used as a model of ferumoxides and be detected by fluorescence. METHODS: To combine and compare the advantages of different microscopic imaging modes, characterization studies were carried out by means of a confocal laser scanning microscope (CLSM), a secondary ion mass spectrometric (SIMS) microscope, and an electron energy loss spectrometric (EELS) microscope. In the case of CLSM, the locations of fluorescent signals inside preparations were determined by factor analysis of biomedical image sequences (FAMIS) and selection of image sequences at emission. RESULTS: By CLSM and FAMIS, we distinguished chelated Eu and Texas Red attached to Fe. By SIMS microscopy, we distinguished Eu and Gd of chlorides and chelates and Fe of a ferumoxide. By EELS microscopy, we distinguished Eu and Gd of chlorides. CONCLUSIONS: Analysis of compounds inside correlative specimens by means of CLSM, SIMS, and EELS microscopes provided complementary results.

Mechanisms of action of liver contrast agents: impact for clinical use.

New contrast agents for magnetic resonance imaging are continually being developed by pharmaceutical companies in order to better image the liver. These agents can be divided into hepatobiliary agents directed to the hepatocytes and nanoparticulate agents directed to the reticulo-endothelial system. After intravenous injection, all these agents concentrate in the liver and induce profound changes in signal intensity. Particulate agents induce predominantly a darkening of the liver parenchyma, while hepatobiliary agents induce a brightening. In both cases, liver-lesion conspicuity is enhanced, leading to a better visualization of the lesion. After a brief description of the principal characteristics of the agents, this paper will attempt to summarize the utility of these agents for the detection and characterization of focal liver disease.

Measurement of liver blood volume using a macromolecular MRI contrast agent at equilibrium.

Liver regional blood volume (LRBV) is altered by several disease states and various drugs. Preliminary studies in the rat, using research MR imaging instruments at 2T and vascular contrast agents, have suggested that MRI may be used to measure LRBV. Our goal was to develop a technique for measuring LRBV using a clinical machine at 1.5 T. This study was performed in the rabbit, using CarboxyMethylDextran Gd-DTPA, a macromolecular contrast agent with a molecular weight of 158 kDa. MRI was performed at 1.5 T, in the plane of the inferior vena cava, with and without flow compensation, before contrast injection and in the steady state after injection. Accuracy and stability of LRBV measurement, over 2 h and with various doses (0.01-0.05 mmol/kg), was tested against a standard Evan's Blue dye-indicator technique. LRBV was 28 +/- 2 mL/100 g when measured by MRI with flow compensation, which is in good agreement with the literature and with the 26 +/- 6 mL/100 g, measured by the Evan's Blue dilution technique. Measurements varied less than 7% over time and less than 9% over the range of doses. LRBV was overestimated using a sequence without flow compensation especially when large doses of contrast agent were injected. This noninvasive MRI technique provides a simple method for measuring liver LRBV and offers new prospects for future physiological and pathological studies.

Gadolinium-ethoxybenzyl-DTPA, a new liver-directed magnetic resonance contrast agent. Absence of acute hepatotoxic, cardiovascular, or immunogenic effects.

RATIONALE AND OBJECTIVES: Gadolinium-ethoxybenzyl-DTPA (Gd-EOB-DTPA) is a recently introduced experimental magnetic resonance (MR) contrast agent for hepatic imaging. Although liver enhancement has been investigated in a number of animal models, tolerance evaluations of Gd-EOB-DTPA injection have been limited. METHODS: The authors investigated acute hepatotoxicity in an isolated perfused rat liver model, cardiovascular effects in the anesthetized rat, and potential immunogenicity of Gd-EOB-DTPA using detection of specific antibodies. RESULTS: Using perfused rat liver model, no significant deviation could be observed for functional parameters, liver enzymes, or potassium release, comparing Gd-EOB-DTPA to a control, but there was a significant choleresis (+250% bile flow). Hemodynamic effects of Gd-EOB-DTPA were observed after femoral bolus injection, but only with relatively high dosages (0.3-0.5 mmol/kg, 10-fold the likely clinical dose in humans). Experimental conditions, idealized for antibody induction, failed to cause an IgG immune response to Gd-EOB-DTPA in the intact rat. CONCLUSIONS: The results further support preliminary conclusions that Gd-EOB-DTPA is a well-tolerated MR contrast agent.