Normal Wistar Rats Research Articles

The influence of chemical structure of phosphonic acids labeled with gallium-68 on their pharmacokinetic properties in animals

68 Ga-labeled phosphonates are of great interest due to their possibility to serve promising agents in nuclear medicine for bone tissue PET imaging. It is known that multidentate aminophosphonate ligands could form much stable chelates with different radiometals as compared to diphosphonates. In this work we studied the pharmacokinetic properties of 68Ga-labeled complexes with two, four and five phosphonate groups (68Ga-HEDP, 68Ga-EDTMP, and 68Ga-DTPMP, respectively) in normal Wistar rats after intravenous administration. It was shown that the structure of phosphonates had a great influence on the biodistribution of 68Ga-HEDP, 68Ga-EDTMP, and 68Ga-DTPMP. Complexes with higher number of aminomethylenephosphonate groups (68Ga-EDTMP and 68Ga-DTPMP) had higher bone uptake than diphosphonate 68Ga-HEDP. In blood 68Ga-HEDP had lower activity than 68Ga-EDTMP and 68Ga-DTPMP, indicating poor stability of diphosphonate-based complex. In other soft organs and tissues 68Ga-EDTMP and 68Ga-DTPMP uptake was slightly lower as compared with 68Ga-HEDP. In conclusion, 68Ga-EDTMP and 68Ga-DTPMP have the potential to be suitable radiotracers for bone tissue PET imaging.

Plasma small extracellular vesicles in hypertensive rats impair reactivity of isolated blood vessels.

Extracellular vesicles (EV) consist of a lipid-bilayered membrane and are typically classified as small EV (sEV or exosome) or large EV (or microvesicle). sEV mediate cell-to-cell communication and play a key role in various disease states. We recently reported that plasma sEV in normotensive Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR), an animal model of human essential hypertension, regulate systemic blood pressure (BP). An abnormal vascular reactivity is involved in the onset and progression of hypertension. In the present study, we tested the hypothesis that plasma sEV may affect the reactivity of isolated blood vessels. sEV were isolated from plasma in male WKY and SHR (WsEV and SsEV, respectively) by precipitation with polyethylene-glycol and ultracentrifugation. The particle distribution and concentration of sEV were measured by a tunable resistive pulse sensing method. Isolated mesenteric arteries from normal male Wistar rats were cultured for 24 hr with WsEV, SsEV, or vehicle. There was no difference in particle distribution and total concentration between WsEV and SsEV. Both SsEV and WsEV had no significant effect on the KCl-induced maximal contraction, while SsEV specifically attenuated contraction induced by noradrenaline compared with WsEV- and vehicle-treatment. In summary, it was for the first time revealed that SsEV attenuate the agonist-induced contractility of isolated blood vessels, which might be at least partly responsible for the BP regulation by SsEV.

High fructose diet-induced metabolic syndrome and the functional abnormalities in the liver and kidney of Wistar albino rats

Background: Metabolic syndrome is the combination of several medical conditions that increase the risk of developing heart diseases, stroke, cancer, non-alcoholic fatty liver, and diabetes mellitus. Different varieties of animal models have been used for the therapeutic studies of diabetes, hyperlipidemia, and kidney diseases. The establishment of appropriate experimental animal models of metabolic syndrome is very important for evaluating the pathophysiology of the disease in humans. Aim and Objective: The aim of the study was to assess the functional abnormalities associated with high fructose diet (HFrD)-induced metabolic syndrome in Wistar albino rats. Materials and Methods: Metabolic syndrome is induced in adult male Wistar albino rats by feeding a combination of HFrD (55%) and fructose enriched water (15%) for 75 days and kept as Group 2 or HFrD group. Normal male Wistar albino rats were kept as normal control. During the entire course of study, weight gain was monitored once a week in both groups. Biochemical investigations such as lipid profile, liver function test, and renal function test were carried out using standard methods. The obtained data were statistically analyzed by students “t-test” and the values were considered statistically significant at p < 0.05. Results: Chronic administration of HFrD resulted in obesity, abnormal hepatic, and renal functions in Wistar rats. Conclusion: Chronic consumption of HFrD produces functional abnormalities in liver and kidney of Wistar rats.

Gastroprotective Effect of Acacia aroma Gill. ex Hook. and Arn. Leaves Extracts in Gastric Ulcer Models in Rats

Background: Peptic ulcer is a disease caused by imbalance between protective and aggressive factors in the gastric mucosa. Acacia aroma Gill. ex Hook. and Arn. (tusca) is widely used in Argentinian’s folk medicine for gastrointestinal disorders. The present study was designed to evaluate the protective effect of two A. aroma leaf extracts, 5% infusion and 10% hydroalcoholic extract in experimental models of acute gastric ulceration in rats. Methods: The gastroprotective action of the extracts was evaluated in absolute ethanol-induced gastric lesion models in adult Westar rats through macroscopic, histological and biochemical analyses of the stomach and gastric wall. We also determined the effects on the gastric juice parameters with a pylorus ligature model in rats. Evaluation of the acute toxicity of each extract was performed in adult normal Wistar rats. All results were statistically analyzed. Results: The lowest effective dose was 150 mg/Kg for each extract. Both of them showed a high protection of the mucosa against absolute ethanol. Pre-treatments with the extracts produced a significant increase in adherent mucus. These extracts showed a free radical scavenging capacity and they caused a significant reduction of the malondialdehyde, reduced glutathione levels, catalase and myeloperoxidase activities. The animals presented no signs of acute toxicity indicating a high safety margin for both extracts. Conclusion: This study shows for the first time the gastroprotective efficacy of 5% infusion and 10% hydroalcoholic extract of A. aroma leaves, highlighting their benefits as a prophylactic approach to maintain the integrity of the gastric mucosa.

Neuroprotection by Insulin-like Growth Factor-1 in Rats with Ischemic Stroke is Associated with Microglial Changes and a Reduction in Neuroinflammation

We and others have shown that insulin-like growth factor-1 (IGF-1) is neuroprotective when administered systemically shortly following stroke. In the current study, we addressed the hypothesis that microglia mediate neuroprotection by IGF-1 following ischemic stroke. Furthermore, we investigated whether IGF-1 modulates pro- and anti-inflammatory mediators in ischemic brain with a special reference to microglia. Ischemic stroke was induced in normal conscious Wistar rats by infusing the vasoconstrictor, endothelin-1 (Et-1), next to middle cerebral artery (MCA). IGF-1 (300 μg) was injected subcutaneously (SC) at 30 and 120 min following stroke. Microglial inhibitor, minocycline, was injected intraperitoneally (IP) at 1 h before stroke (25 mg/kg) and 11 h after stroke (45 mg/kg). Post-stroke IGF-1 treatment reduced the infarct size and increased the sensorimotor function which coincided with an increase in the number of ameboid microglia in the ischemic cortex. Minocycline treatment abrogated the increase in ameboid microglia by IGF-1, while the effect of IGF-1 in the reduction of infarct size was only partially affected. IGF-1 suppressed mRNA expression of inducible nitric oxide synthase (iNOS) and interleukin (IL)-1β in the ischemic hemisphere, while in purified microglia, only iNOS expression levels were reduced. Our findings show that microglia are a target for IGF-1 and that neuroprotection by IGF-1 coincides with down-regulation of inflammatory mediators which could be instrumental to the beneficial effects.

Cortical Somatosensory Neurons in WAG/Rij Rats Transform Firing Evoked by Simulation of Posterior Thalamic Nucleus from Tonic to Phasic at Age of 6 Months.

Functional peculiarities of paralemniscal subdivision of the thalamocortical system were examined in normal Wistar and in WAG/Rij rats genetically prone to absence epilepsy. In 6-7-month-old WAG/Rij characterized by developed epileptic activity, the response of cortical somatosensory neurons to single electrical stimulation of the posterior thalamic nucleus was phasic, whereas in normal Wistar rats, similar reaction was tonic. The study views this phasic response as neural equivalent of spike-wave discharges known as typical EEG symptom of absence epilepsy.

Flaxseeds (L. Usitatissimum) attenuates blood pressure, acetylcholinesterase activity and oxidative stress in ouabain-induced hypertension in normal Wistar rats

PurposeThe purpose of this study is to evaluate the effects of flaxseed (L. usitatissimum [Linn]) on blood pressure, redox status markers and acetylcholinesterase enzyme activity in ouabain-induced hypertension in normal Wistar rats.Design/methodology/approachMale Wistar rats weighing 250 ± 7 g (n = 24) fed with an experimental diet containing 20 per cent casein were divided into three groups (n = 8) and received a daily subcutaneous injection of either 0.9 per cent saline solution (T group) or 10 µg/kg/day of ouabain diluted in saline solution-treated Oub-Lu or not with 1 per cent of flaxseed (L. usitatissimum) mixed in the diet for 21 days.FindingsThe results showed that treatment with flaxseed had a significant effect (p < 0.05) in decreasing systolic, diastolic blood pressure, mean arterial pressure and the heart rate in hypertensive rats. Total and non-HDL cholesterol levels were reduced by –26 and –35 per cent; p = 0.04, respectively. Concentrations of thiobarbituric acid-reactive substances were significantly decreased by –85 and –42 per cent (p = 0.001 and p = 0.04), respectively in the plasma and heart. Nitric oxide levels were increased in the aorta (+ 63 per cent; p = 0.001). Moreover, in the heart and aorta, a significant increase was noted in the thiol contents (+81 and +69 per cent; p = 0.001, respectively), glutathione peroxidase (+50 per cent; p = 0.03 and p = 0.01, respectively) and acetylcholinesterase activities (75 and +19 per cent, respectively; p = 0.001 and p = 0.04).Originality/valueThese results suggest hypotensive, cardiomoderating and antioxidant effects of flaxseed in ouabain-induced hypertension in the rat. In addition, it promotes a significant increase of the acetylcholinesterase activity in tissues.

Diuretic activity of ethanol extract of Mirabilis jalapa (Linn.) leaf in normal male Wistar rats

Background: Ethanol extract of Mirabilis jalapa leaf (EEMJL) has been used in the folk medicine of Nigeria as diuretics without any scientific evidence.Aim: Ethanol extract of Mirabilis jalapa leaf at 200, 400 and 600 mg/kg body weight was investigated for diuretic activity in male Wistar rats.Setting: Fresh leaf of M. jalapa was collected from a farmland at the Alanamu area in Ilorin, Kwara State, Nigeria, authenticated and processed for the study.Methods: Thirty male rats (231.50 g ± 13.51 g) were assigned into five groups (A–E) of six rats each. Rats in group A (control) received 1.0 mL of physiological saline (the vehicle). Animals in groups B (positive control), C, D and E received 1.0 mL equivalent to 100 mg/kg body weight of furosemide, 200, 400 and 600 mg/kg body weight of EEMJL, respectively. All administrations were done by oral gavage. The animals were monitored for indicators of diuresis for 5 h using standard methods.Results: Ethanol extract of Mirabilis jalapa leaf dose-dependently increased (p &lt; 0.05) urine volume, urine concentrations of Na+, K+ and Cl− and decreased (p &lt; 0.05) the body weight of the animals. Ethanol extract of Mirabilis jalapa leaf increased the urine pH, saliuretic activity, saliuretic index, Na+ index, K+ index, Cl− index, diuretic action (diuretic index), kaliuretic index, Lipschitz value and percentage saline load excreted, whereas the latency of urination, natriuretic index, carbonic anhydrase inhibitory activity and carbonic anhydrase inhibition index were decreased. The EEMJL treatment-related changes in these parameters were essentially similar to those of the furosemide-treated animals.Conclusion: This study has thus validated diuretic activity of M. jalapa leaf with the 600 mg/kg body weight of EEMJL being the most effective.

Amelioration of antioxidant potential, toxicity, and antihyperglycemic activity of Hippophae salicifolia D. Don leaf extracts in alloxan-induced diabetic rats.

Efficacy of several plant extracts in the clinical research for modulating oxidative stress correlated with diabetes mellitus (DM) is well documented. In the present study, we investigated the in vitro antioxidant activity, toxicity, and anti-diabetic activity of methanolic extract of Hippophae salicifolia leaves in normal and alloxan-induced diabetic wistar rats. H. salicifolia leaves were found to be rich in antioxidants. The acute toxicity test of methanolic extract of H. salicifolia leaves revealed that the median lethal dose (LD50) was found to be 3.92g/kg body weight in mice. Administration of H. salicifolia leaves at 200mg/kg and 400mg/kg in alloxan-induced diabetic rats illustrated significant reduction (22% and 39%, respectively) in fasting blood glucose compared to diabetic control. Both the doses were found to be effective when compared to diabetic rats. The Hippophae-treated diabetic rats showed significant increase in the endogenous antioxidant enzymes, superoxide dismutase (50% and 74%, respectively), glutathione peroxidase (57% and 41%, respectively) and decrease in malondialdehyde (33% and 15%, respectively) levels. These results suggested that the methanolic leaf extract of H. salicifolia enhanced the antioxidant defence against reactive oxygen species produced under hyperglycaemic conditions.

Electroconvulsive shock restores the decreased coverage of brain blood vessels by astrocytic endfeet and ameliorates depressive-like behavior

BackgroundAlthough growing evidence indicates that ECT affects astrocytes, the exact mechanisms of the therapeutic effect of ECT are still unknown. Astrocytic endfeet express the water channel aquaporin (AQP) 4 abundantly and ensheath brain blood vessels to form gliovascular units. It has been shown that the coverage of blood vessels by AQP4-immunostained endfeet is decreased in the prefrontal cortex (PFC) of patients with major depression. This study was made to determine whether ECT restores the astrocytic coverage of blood vessels with amelioration of depressive symptoms. MethodsAfter electroconvulsive shock (ECS) administration to rats, the forced swimming test (FST) and Y-maze test were performed. Subsequently, immunofluorescence analysis was conducted to measure the coverage of blood vessels by astrocytic endfeet in the PFC and hippocampus by using the endothelial cell marker lectin and anti-AQP4 antibody. We also performed Western blot to examine the effects of ECS on the hippocampal expression of AQP4 and the tight junction molecule claudin-5. ResultsGunn rats showed learned helplessness and impaired spatial working memory, compared to normal control Wistar rats. ECS significantly improved the depressive-like behavior. Gunn rats showed a decrease in astrocytic coverage of blood vessels, that was significantly increased by ECS. ECS significantly increased expression of AQP4 and claudin-5 in Gunn rats. ConclusionsECS increased the reduced coverage of blood vessels by astrocytic endfeet in the mPFC and hippocampus with amelioration of depressive-like behavior. Therefore, therapeutic mechanism of ECT may involve restoration of the impaired gliovascular units by increasing the astrocytic-endfoot coverage of blood vessels.

Biochemical effect of aqueous extract of Dialium Guineense stem bark on oxidative status of normal wistar rats

The present study was undertaken to investigate the biochemical effects of aqueous stem bark extract of D. guineense on activities of antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glucose 6-phosphate dehydrogenase (G6PDH)), and malondialdehyde (MDA) and total protein concentrations in normal Wistar rats. Ten adult male Wistar rats weighing 150 to 180 g were randomly assigned to two groups of five rats each: control group and observation group. The observation group received 1000 mg/kg body weight, bwt, of aqueous extract orally for twenty-eight days, and assays were performed on weekly basis. Results of phytochemical analyses of the plant stem bark revealed the presence of tannins (3.76 ± 0.31 %), alkaloids (1.22 ± 0.06 %), phenols (1.40 ± 0.03 %), flavonoids (0.92 ± 0.03 %), saponins (0.18 ± 0.02 %), glycosides (0.04 ± 0.01 %) and steroids (0.04 ± 0.01 %). There was no significant difference in the concentration of total protein between the two groups (p > 0.05). The concentration of MDA was significantly lower in observation group than in control group (p < 0.05). However, the activities of G6PDH, SOD, CAT and GPx were significantly higher in observation group than in control group (p < 0.05). The extract potentiated the activities of G6PDH, SOD, catalase and GPx.

Hypolipidemic effect of ethanol extract from Mesona chinensis Benth. in high fat diet-induced obesity mice

Hypolipidemic effect of ethanol extract from Mesona chinensis Benth. in high fat diet-induced obesity mice

Baillonella toxisperma improves sexual performance and protects against stress-induced reproductive dysfunction in male Wistar rats

Baillonella toxisperma Pierre (Sapotaceae) is a medicinal plant widely used in Central Africa against several diseases including erectile dysfunction and male infertility. However, no study dealing with these male reproductive dysfunctions has been published until now. Accordingly, the present study was undertaken. It evaluated the capacity of an aqueous extract of stem bark of B. toxisperma (BT) at 75, 150 and 300 mg/kg/d to induce aphrodisiac effects and prevent the stress-induced reproductive dysfunction in males using normal non-experienced (an 8-day oral treatment) and stressed (a 6-h/day immobilization stress for 35 consecutive days)male Wistar rats. Both in normal and stressed animals, BT at the doses of 150 and 300 mg/kg decreased (p &lt; 0.05) the mount and intromission latencies, and increased (p &lt; 0.05) the number of total penile licking, mount and intromission as well as ejaculation frequencies. In stressed animals, a significant (p &lt; 0.05) increase in sperm levels, sperm mobility as well as in the relative weight of androgen-dependent organs (testis, epididymis and seminal vesicles) was observed at the same doses compared with the stressed control. These results suggest that this aqueous extract of B. toxisperma might endow with aphrodisiac and androgenic properties in normal and stressed male Wistar rats.

TMEM16A is implicated in the regulation of coronary flow and is altered in hypertension

Coronary artery disease leads to ischaemic heart disease and ultimately myocardial infarction. Thus, it is important to determine the factors that regulate coronary blood flow. Ca2+ -activated chloride channels contribute to the regulation of arterial tone; however, their role in coronary arteries is unknown. The aim of this study was to investigate the expression and function of the main molecular correlate of Ca2+ -activated chloride channels, TMEM16A, in rat coronary arteries. We performed mRNA and protein analysis, electrophysiological studies of coronary artery myocytes, and functional studies of coronary artery contractility and coronary perfusion, using novel inhibitors of TMEM16A. Furthermore, we assessed whether any changes in expression and function occurred in coronary arteries from spontaneously hypertensive rats (SHRs). TMEM16A was expressed in rat coronary arteries. The TMEM16A-specific inhibitor, MONNA, hyperpolarised the membrane potential in U46619. MONNA, T16Ainh -A01, and Ani9 attenuated 5-HT/U46619-induced contractions. MONNA and T16Ainh -A01 also increased coronary flow in Langendorff perfused rat heart preparations. TMEM16A mRNA was increased in coronary artery smooth muscle cells from SHRs, and U46619 and 5-HT were more potent in arteries from SHRs than in those from normal Wistar rats. MONNA diminished this increased sensitivity to U46619 and 5-HT. In conclusion, TMEM16A is a key regulator of coronary blood flow and is implicated in the altered contractility of coronary arteries from SHRs.

Extracts of Guiera senegalensis J.F. Gmel (Combretaceae) Galls Ameliorates Streptozotocin-Induced Diabetes Mellitus Rats Status

Background: A good number of medicinal and dietary plants are used for diabetes treatment in Burkina Faso.&#x0D; Aim of the Study: The present study aimed to investigate the antidiabetic activity of Guiera senegalensis galls extracts and its potential mechanisms in streptozotocin-induced diabetic rats.&#x0D; Methodology: The methanol extract was administered by gavage to healthy Wistar rats for the determination of toxicity, to normal and diabetic Wistar rats for the determination of glucose reduction level, lipid profile, insulin level and glycaemic parameters in serum. The histology and immunohistochemistry of the pancreas were also determined.&#x0D; Results: The acute toxicity results showed that the medium lethal dose (LD50) of the methanol galls extract of Guiera senegalensis is greater than 2000 mg/kg body weight in rats. Guiera senegalensis methanolic extract (250 mg/kg) and the tolbutamide (100 mg/kg) recorded a significantly (p &lt; 0.05) lower level of triglyceride compared to the diabetic group. The methanol extract (250 and 500 mg/kg pc) significantly (p &lt; 0.05) decreased the blood glucose level and increased the serum insulin level in diabetic rats. Interestingly, improved ß-cell function and antioxidant status were also observed in G. senegalensis-treated diabetic rats when compared to tolbutamide-treated diabetic rats.&#x0D; Conclusion: These data showed direct evidence that G. senegalensis has antidiabetic activity by decreasing blood glucose level, improving insulin secretion and β-cell functions and modulating antioxidant status.

Unequivocal evidence for endogenous geranylgeranoic acid biosynthesized from mevalonate in mammalian cells

Geranylgeranoic acid (GGA) has been reported to induce autophagic cell death via upregulation of lipid-induced unfolded protein response in several human hepatoma-derived cell lines, and its 4,5-didehydro derivative has been developed as a preventive agent against second primary hepatoma in clinical trials. We have previously reported that GGA is a natural diterpenoid synthesized in several medicinal herbs. Here, we provide unequivocal evidence for de novo GGA biosynthesis in mammals. First, with normal male Wistar rats, the levels of GGA in liver were found to be far greater than those in other organs analyzed. Second, we demonstrated the metabolic GGA labeling from the 13C-labeled mevalonolactone in the human hepatoma-derived cell line, HuH-7. Isotopomer spectral analysis revealed that approximately 80% of the cellular GGA was newly synthesized from mevalonate (MVA) in 12 h and the acid picked up preexisting farnesyl diphosphate (FPP) and geranylgeranyl diphosphate (GGPP), suggesting that GGA is derived from FPP and GGPP through the MVA pathway. Third, zaragozic acid A, a squalene synthase inhibitor, induced dose-dependent upregulation of endogenous GGA content in HuH-7 cells and their concomitant cell death. These results strongly suggest that a cancer-preventive GGA is biosynthesized via the MVA pathway in mammals.

Ce-141-labeled DOTMP: A theranostic option in management of pain due to skeletal metastases.

Owing to its favorable radioactive decay characteristics (T1/2 =32.51 d, Eβ [max]=434.6keV [70.5%] and 580.0keV [29.5%], Eγ =145.4keV [48.5%]), 141 Ce could be envisaged as a theranostic radionuclide for use in nuclear medicine. The present article reports synthesis and evaluation of 141 Ce complex of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylenephosphonic acid (DOTMP) as a potent theranostic agent targeting metastatic skeletal lesions. Ce-141 was produced with 314±29MBq/mg (n=6) specific activity and >99.9% radionuclidic purity (n=6). Around 185MBq dose of [141 Ce]Ce-DOTMP was synthesized with 98.6±0.5% (n=4) radiochemical yield under optimized conditions of reaction, and the preparation showed adequately high in vitro stability. Biodistribution studies in normal Wistar rats demonstrated significant skeletal localization and retention of injected activity (2.73±0.28% and 2.63±0.22% of injected activity per gram in femur at 3hours and 14 days post-injection, respectively) with rapid clearance from non-target organs. The results of biodistribution studies were corroborated by serial scintigraphic imaging studies. These results demonstrate the potential utility of 141 Ce-DOTMP as a theranostic molecule for personalized patient care of cancer patients suffering from painful metastatic skeletal lesions.

Enhancement of211At Uptake via the Sodium Iodide Symporter by the Addition of Ascorbic Acid in Targeted α-Therapy of Thyroid Cancer

211At is an α-emitter that has similar chemical properties to iodine and is used in targeted α-therapy. In the present study, we added ascorbic acid (AA) to 211At solution to increase the radiochemical purity of astatide and evaluated its efficacy against differentiated thyroid cancer, which is characterized by the expression of sodium/iodide symporter (NIS). Methods: Crude 211At solution (AA(−)) and 211At solution treated with AA (AA(+)) were prepared. Uptake by the thyroid was compared between the 2 solutions in normal male Wistar rats (n = 6). Cellular uptake in K1-NIS cells was analyzed under the AA(+) and AA(−) conditions. AA(+) was injected at 3 doses into K1-NIS xenograft mice: 1 MBq (n = 6), 0.4 MBq (n = 6), and 0.1 MBq (n = 6), and vehicle was injected into control mice (n = 6). The treatment effects were compared among the 4 groups. Results: Uptake by the thyroid was significantly enhanced in rats injected with the AA(+) as compared with those injected with AA(−). Cellular uptake analysis showed significantly increased uptake of 211At by the K1-NIS cells under the AA(+) condition as compared with the AA(−) condition. In the mouse xenograft model, the K1-NIS tumors showed significant accumulation of 211At at 3 and 24 h after administration (22.5 ± 10.4 and 12.9 ± 6.8 percentage injected dose, respectively). Tumor growth was immediately inhibited in a dose-dependent manner after administration of 211At. In the survival analysis, the 211At groups (0.1, 0.4, and 1 MBq) showed significantly better survival than the control group. Conclusion: Uptake of 211At was enhanced in differentiated thyroid cancer cells as well as the normal thyroid using 211At solution treated with AA. The method also showed dose-dependent efficacy against the K1-NIS xenografts, suggesting its potential applicability to targeted α-therapy.

Effect of "edible clay" (takere) suspension on serum lipid profiles and atherogenic indices of normal Wistar rats.

This study was undertaken to ascertain the effect of an aqueous suspension of a commonly available preparation of edible clay (“takere”) on serum lipid profiles and atherogenic indices of normal Wistar rats. Ninety‐five adult Wistar rats of average weight of 100 g were assigned into seven groups. Group 1 (Baseline) was immediately sacrificed at the commencement of study; Group 2 (Control) daily received distilled water, orally; and Groups 3 to 7 received via the same route (per body weight), 125 mg/kg (T125), 250 mg/kg (T250), 500 mg/kg (T500), 1,000 mg/kg (T1000), and 2,000 mg/kg (T2000) of the takere suspension, respectively, for 28 days. In week 1, the treatments significantly (p < 0.05) lowered the levels of serum triglyceride (by T250, T1000, and T2000), VLDL cholesterol (by T250, T1000, and T2000), and atherogenic index of plasma (AIP; by T250) and significantly (p < 0.05) raised the levels of serum HDL (T250), LDL (T250 and T2000), non‐HDL (T2000) cholesterols, atherogenic coefficient (AC; T2000), cardiac risk ratio (CRR; T2000), and Castelli's risk index II (CRI‐II; T2000) of the rats. In week 2, the treatments significantly (p < 0.05) lowered the levels of serum triglyceride (T2000), HDL (T125, T500, T1000, and T2000), VLDL (T2000) cholesterols and significantly (p < 0.05) raised levels of serum LDL (T125, T1000, and T2000), non‐HDL (T125, T1000, and T2000) cholesterols, AC (T125, T500, and T1000), CRR (T125, T500, and T1000), CRI‐II (T125 and T1000), AIP (T125, T500, and T1000) of the rats. In week 4, the treatments significantly (p < 0.05) raised the levels of serum total (T500 and T2000), HDL (T2000), non‐HDL (T500 and T1000) cholesterols, AC (T500), CRR (T500), and CRI‐II (T500). This result indicates that the consumption of takere suspension may have adverse effects on serum lipid profiles and atherogenic indices of Wistar rats, at least at the doses administered in this study.

Synthesis and evaluation of 99mTc-analogues of [123/131I]mIBG prepared via [99mTc][Tc(CO)3(H2O)3]+ synthon for targeting norepinephrine transporter

Introductionmeta-[123/131I]Iodobenzylguanidine (mIBG) is a clinical agent used for imaging neuroendocrine tumors, where uptake in tumor is via active transport mechanism through norepinephrine transporters (NET). Our group in past have evaluated a 99mTc-analogue of the above tracer, based on 99mTc-4 + 1 labeling approach, which exhibited significant affinity for NET but suffered from reduced specific uptake in comparison to reference standard no-carrier-added (n.c.a.) [125I]mIBG. The present work attempts to synthesize two new 99mTc-analogues of the radio-iodinated derivative following [99mTc]Tc(CO)31+ approach with an aim to improve the above specific uptake content. MethodsTwo different precursors, xylylenediamine and 1,3-bis(chloromethyl)benzene, were synthetically modified to yield meta-functionalized benzylguanidine derivatives bearing iminodiacetate (IDA) and aminoethylglycine (AEG) tridentate chelating moieties, respectively. These ligands were labeled with technetium-99m via [99mTc][Tc(CO)3(H2O)3]+ synthon to form desired radioactive complexes 9 and 10. The radiolabeling yields of the complexes obtained were >90% as confirmed by radio-HPLC. The HPLC purified complexes were used for in vitro and in vivo evaluation to understand the true biological efficacy. Structural characterization of the radiolabeled complexes was carried after synthesizing and characterizing their Re-analogues. ResultsCell uptake studies with the radiolabeled complexes in SK-N-SH neuroblastoma cell lines revealed reduced uptake in the cells (<1% of incubated radioactivity/106 cells) in comparison to n.c.a. [125I]mIBG (~12%). However, limited specificity (~60%) was observed for the complexes as ascertained through desmethylimipramine (DMI) inhibition. Biodistribution studies in normal Wistar rats exhibited desired non-target clearance pharmacokinetics for the complexes but in vivo NET efficacy in myocardium for the neutral complex 10 could not be established. ConclusionsTridentate [99mTc]Tc(CO)31+ chelation approach severely affects biological behavior of the present small bioactive molecule under study to a significant extent in comparison to monodentate ligation in 99mTc-4 + 1 strategy.