Daniel F. Sousa

Betulinic Acid, a Natural Pentacyclic Triterpenoid, Prevents Abdominal Fat Accumulation in Mice Fed a High-Fat Diet

In the search for potential antiobese agents from natural sources, this study investigated the effects of betulinic acid (BA), a pentacyclic triterpene from Clusia nemorosa L. (Clusiaceae), in mice on a high-fat diet (HFD). Adult male Swiss mice (n = 8) treated or not with BA (50 mg/L, in drinking water) were fed a HFD during 15 weeks. Mice treated with BA and fed a HFD showed significantly (P < 0.05) decreased body weights, abdominal fat accumulation, blood glucose, plasma triglycerides, and total cholesterol relative to their respective controls fed no BA. Additionally, BA treatment, while significantly elevating the plasma hormone levels of insulin and leptin, decreased the level of ghrelin. However, it caused a greater decrease in plasma amylase activity than the lipase. These findings suggest that BA has an antiobese potential through modulation of fat and carbohydrate metabolism, and it may be a suitable lead compound in the treatment of obesity.

Effects of Bixa orellana L. Seeds on Hyperlipidemia

Bixa orellana L., urucum, or urucu, a native tropical tree of Central and South American rain forests is used to treat various diseases in popular medicine. In Ceará, Northeast of Brazil, the seeds of urucum have been used for the treatment of high lipid blood levels. The present study investigated the effects of the aqueous extract from Bixa orellana seeds (AEBO) in mice with hyperlipidemia induced by tyloxapol, fructose and ethanol. In hyperlipidemia induced by Triton WR1339, 400 and 800 mg/kg AEBO reduced triglycerides (TG) serum levels at 24 h and 48 h. In the study of hypertriglyceridemia induced by fructose, AEBO in doses of 400 mg/kg and 800 mg/kg reduced TG levels by 48.2% and 48.7%, respectively. Finally, the ethanol experimental model with 400 mg/kg AEBO promoted a reduction of 33.6% of TG levels, while the 800 mg/kg concentration reduced hypertriglyceridemia in 62.2%. In conclusion, the aqueous extract of the seeds of Bixa orellana was capable of reversing the hypertriglyceridemia induced by Triton, fructose and ethanol, demonstrating a hypolipidemic effect. However, further studies are necessary to discover the precise mechanism of action. Copyright

Inhibitory effects of sertraline in rat isolated perfused kidneys and in isolated ring preparations of rat arteries.

Objectives  Sertraline is often prescribed to patients suffering with end stage renal disease, but its action on kidney has not been investigated. We aimed to investigate the pharmacological action of sertraline on rat kidney with emphasis on the underlying mechanisms involved in the vascular actions of the drug.

Sodium bicarbonate treatment prevents gastric emptying delay caused by acute exercise in awake rats.

Physical exercise, mainly after vigorous activity, may induce gastrointestinal dysmotility whose mechanisms are still unknown. We hypothesized that physical exercise and ensuing lactate-related acidemia alter gastrointestinal motor behavior. In the present study, we evaluated the effects of short-term exercise on gastric emptying rate in awake rats subjected to 15-min swimming sessions against a load equivalent to 5% of their body weight. After 0, 10, or 20 min of exercise testing, the rats were gavage fed with 1.5 ml of a liquid test meal (0.5 mg/ml of phenol red in 5% glucose solution) and euthanized 10 min postprandially to measure fractional gastric dye recovery. In addition to inducing acidemia and increasing blood lactate levels, acute exercise increased (P < 0.05) gastric retention. Such a phenomenon presented a positive correlation (P < 0.001) between blood lactate levels and fractional gastric dye recovery. Gastric retention and other acidbase-related changes were all prevented by NaHCO3 pretreatment. Additionally, exercise enhanced (P < 0.05) the markers progression through the small intestine. In anesthetized rats, exercise increased (P < 0.05) gastric volume, measured by a balloon catheter in a barostat system. Compared with sedentary control rats, acute exercise also inhibited (P < 0.05) the contractility of gastric fundus strips in vitro. In conclusion, acute exercise delayed the gastric emptying of a liquid test meal by interfering with the acid-base balance.

Towards a better understanding of Ipomoea asarifolia toxicity: evidence of the involvement of a leaf lectin.

Natural intoxication of livestock by ingestion of Ipomoea asarifolia leaves has been reported to occur widely in Brazil. Previous studies carried out by our research group provided strong evidence that a lectin could be involved with the toxic properties of I. asarifolia. To reinforce this hypothesis, a lectin-enriched fraction (LEF) was isolated from I. asarifolia leaves and its toxic effects were assessed. Leaves of I. asarifolia were excised from plants growing widely in the field, mechanically wounded and maintained in a chamber at 25 ± 3 °C for 72h in the dark, under near 100% relative humidity. The leaf proteins were extracted, ammonium sulfate precipitated, chromatographed on DEAE-cellulose and Phenyl-Sepharose to produce LEF that under SDS-PAGE showed a molecular mass of 44.0 kDa and after N-terminal amino acid analysis a primary sequence composed of AGYTPVLDIGAEVLAAGEPY. The in vivo toxicity of LEF assessed by intraorbital injection in mice showed induced severe uncoordinated movements without death. LEF reduced the muscular contraction in a dose depend way and at 29.8 μg/mL (CE(50)) it produces 50% inhibition of contraction, suggesting that LEF blunts autonomic neurotransmission. Isolated rat kidneys were perfused with LEF and no effects on the perfusion pressure or renal vascular resistance were observed, but urinary flow and glomerular filtration rate increased. Moreover, the percentage of tubular transport of Na(+), K(+) and Cl(-) decreased. Histological examination of the kidneys perfused with LEF exhibited little alterations. These toxic effects observed above were concomitant with the increase of LEF hemagglutination activity, which strongly suggest that one of the toxic principles of I. asarifolia is a lectin present in its leaves.

Renal- and calcium-dependent vascular effects of Polybia paulista wasp venom

In the present study, the effects of Polybia paulista venom (PPV) on renal and vascular tissues were investigated. Isolated kidneys perfused with PPV (1 and 3 μg/mL) had increased perfusion pressure, renal vascular resistance, urinary flow, and glomerular filtration rate; and reduced sodium tubular transport. Histological evaluation demonstrated deposits of proteins in Bowmans space and tubular lumen, and focal areas of necrosis. The venom promoted a cytotoxic effect on Madin-Darby canine kidney (MDCK) cells. A significant increase in lactic dehydrogenase levels was observed in response to venom exposure. In isolated mesenteric vascular beds, pressure and vascular resistance augmented in a dose-dependent manner. PPV increased the contractility of aortic rings maintained under basal tension. This contractile response was inhibited when preparations were maintained in Ca2+-free medium. Likewise, verapamil, a voltage-gated calcium channel blocker, also inhibited the contractile response. In this study, phentolamine, a blocker of α-adrenergic receptor blocker, significantly reduced the contractile effect of PPV in the aortic ring. In conclusion, PPV produced nephrotoxicity, which suggests a direct effect on necrotic cellular death in renal tubule cells. The vascular contractile effect of PPV appears to involve calcium influx through voltage-gated calcium channels via adrenergic regulation.

Renal and vascular effects of Crotalus durissus cumanensis venom and its crotoxin fraction

In this study, we evaluated the actions of Crotalus durissus cumanensis venom (CDCmV), and its crotoxin (Crtx) fraction, on renal and vascular functions in Wistar rats. In isolated perfused kidneys, CDCmV (10 µg/mL) significantly increased the perfusion pressure (PP) from 110.7 ± 2.4 to 125.3 ± 2.8 mmHg after 30 minutes. This effect was accompanied by an increased renal vascular resistance (RVR) from 5.4 ± 0.1 to 6.2 ± 0.2 mmHg/mL.g-1.min-1. We observed decreases in urinary flow (UF) from 0.13 ± 0.01 to 0.05 ± 001 mL.g-1.min-1 and glomerular filtration rate (GFR) from 0.66 ± 0.06 to 0.18 ± 0.02 mL.g-1.min-1. Crtx did not change PP or RVR, but diminished GFR (from 0.65 ± 0.05 to 0.26 ± 003 mL.g-1.min-1) and UF (from 0.11 ± 0.008 to 0.09 ± 0.008 mL.g-1.min-1). Both CDCmV and Crtx reduced the percentage of tubular transport of sodium, chloride and potassium. The cytotoxicity of these substances against MDCK cells was tested by the MTT method: only CDCmV caused a decrease in the cell viability with an IC50 of 5.4 µg/mL. In endothelium-intact isolated aortic rings, CDCmV (0.1 to 30 µg/mL) increased the sustained phenylephrine-induced contraction to a value of 130.0 ± 6.6% of its corresponding control, but showed a relaxant effect in endothelium-denuded preparations. Similar results were observed in aortic rings contracted with potassium (40 mM). Crtx was ineffective in aortic ring assays. Thus, it is reasonable to suggest that the renal effects induced by the CDCmV may be due to its influence on the endotheliums ability to release factors that can alter the contractile behavior of vascular smooth muscle. In conclusion, CDCmV is toxic to kidney cells. It changes parameters of the renal function including the glomerular filtration rate, renal vascular resistance and tubular transport. The actions induced by CDCmV also involve endothelium-dependent vasoactive properties. Their effects may be only partially attributed to Crtx.

Antivenom action on renal effects induced by Thalassophryne nattereri venom

Thalassophryne nattereri (niquim) is a venomous fish responsible for numerous accidents involving fishermen in northern and northeastern Brazil. The aim of the present investigation was to evaluate the action of antivenom on renal effects caused by Thalassophryne nattereri venom. Isolated kidneys of Wistar rats were perfused with a previously dialyzed Krebs-Henseleit solution containing 6 g% bovine serum albumin. The antivenom action was studied through perfusion pressure (PP), renal vascular resistance (RVR), urinary flow (UF) and glomerular filtration rate (GFR). The niquim venom (1 µg/mL), the antivenom alone (1 µg/mL) or the venom incubated with antivenom were added to the system 30 minutes after the beginning of each perfusion. Previous works have shown venom induced-alterations of renal function parameters. In the isolated rat kidney, T. nattereri venom (1 µg/mL) increased the perfusion pressure and renal vascular resistance at 60, 90 and 120 minutes. UF and GFR also increased at 60, 90 and 120 minutes when compared with the control group; however, no effects were observed on the percent of sodium (%TNa+control = 81.1 ±0.86; %TNa+60 = 78.04 ±1.18; %TNa+90 = 76.16 ±3.34; %TNa+120 = 79.49 ±0.87) and potassium (%TK+control = 72.29 ±1.12; %TK+60 = 75.41 ±0.65; %TK+90 = 71.23 ±2.55; %TK+120 = 76.62 ±1.04) tubular transport. The administration of the antivenom (1 µg/mL) incubated with venom (1 µg/mL) reduced the changes in PP, RVR, UF and GFR provoked by Thalassophryne nattereri venom. The group perfused with venom alone showed a moderate deposit of a proteinaceous material in the tubules and urinary space. The group perfused with the antivenom presented similar results to the control group. In conclusion, the antivenom was able to decrease the effects induced by T. nattereri venom in isolated rat kidney.

The renal effects and initial characterization of venom from Philodryas nattereri Steindachner, 1870

Highlights • We investigated the effect of P. nattereri venom on the isolated perfused kidney.• We study the mechanism of cytotoxicity of venom on renal epithelial cells.• We demonstrated P. nattereri venom is composed for 86.3% of proteins.• The venom of is capable of changing the kidney functional parameters.