Alpha-terpineol complexed with beta-cyclodextrin reduces damages caused by periodontitis in rats.

BACKGROUND AND OBJECTIVE: This study aimed to assess the effectiveness of the treatment with alpha-terpineol (αTPN) complexed with beta-cyclodextrin (ßCD) on oral, blood, and hepatic parameters in ligature-induced periodontitis. MATERIAL AND METHODS: Forty female rats were distributed among the following groups: control (vehicle solution), periodontitis (ligature + vehicle solution), 5 mg/kg of αTPN-ßCD (ligature), and 25 mg/kg of αTPN-ßCD (ligature). Compounds were administered daily via intraperitoneal injection over a 20-day period. Periodontitis was induced with the bilateral insertion of ligatures around the first lower molars of each rat. Oral parameters, as well as blood biomarkers, were measured: histopathological assessment of the hepatic tissue was carried out using light and transmission electron microscopy. RESULTS: The treatment with αTPN-ßCD significantly improved several oral parameters and blood biomarkers in comparison with rats with periodontitis. In addition, the treatment with αTPN-ßCD significantly ameliorated the steatosis score and reduced the number of lipid droplets and the amount of foamy cytoplasm in the hepatocytes of rats with periodontitis. CONCLUSION: The results obtained suggest that the treatment with αTPN-ßCD improves several oral and blood parameters in rats with experimental periodontitis. In addition, hepatic alterations caused by periodontitis were ameliorated in the rats treated with αTPN-ßCD.

Antimicrobial activity of Phyllanthus amarus Schumach. & Thonn and inhibition of the NorA efflux pump of Staphylococcus aureus by Phyllanthin.

The aim of this study was to evaluate the antimicrobial activity of ethanoic extract of P. amarus (PAEE) and its compound Phyllanthin, as well as, investigate if these natural products could modulate the fluoroquinolone-resistance in S. aureus SA1199-B by way of overexpression of the NorA efflux pump. Microdilution tests were carried out to determine the minimal inhibitory concentration (MIC) of the PAEE or Phyllanthin against several bacterial and yeast strains. To evaluate if PAEE or Phyllanthin were able to act as modulators of the fluoroquinolone-resistance, MICs for Norfloxacin and ethidium bromide were determined in the presence or absence of PAEE or Phyllanthin against S. aureus SA1199-B. PAEE showed antimicrobial activity against Gram-negative strains, meanwhile Phyllanthin was inactive against all strains tested. Addition of PAEE or Phyllanthin, to the growth media at sub-inhibitory concentrations enhanced the activity of the Norfloxacin as well as, Ethidium Bromide, against S. aureus SA1199-B. These results indicate that Phyllanthin is able to modulate the fluoroquinolone-resistance possibly by inhibition of NorA. This hypothesis was supported by in silico docking analysis which confirmed that Phyllantin is a NorA ligand. Thus, this compound could be used as a potentiating agent of the Norfloxacin activity in the treatment of infections caused by fluoroquinolone-resistant S. aureus.

Periodontitis causes abnormalities in the liver of rats.

BACKGROUND: Periodontitis not only causes injury to the periodontium, but also damages other tissues such as: articulate, renal, cardiac, and hepatic. The objective of this study was to investigate periodontitis induced alterations in liver function and structure using an experimental model. METHODS: Twenty female rats (Rattus norvegicus) were allocated into two groups: control and periodontitis. Gingival bleeding index and oxidative stress parameters and specific circulating biomarkers were measured. Immunohistochemistry was carried out using alkaline phosphatase (AlkP) staining of the liver. Hepatic tissues, cytokines, and lipid contents were measured. Histopathologic evaluation of the liver was carried out using light and electron microscopy. RESULTS: Liver histopathologic and immunohistochemistry assessment showed increase in steatosis score, and presence of binucleate hepatocytes and positive cells for AlkP in periodontitis versus control group. Ultrastructural evaluation showed significant increase in size and number of lipid droplets (LD), distance between the cisterns of rough endoplasmic reticulum (RER), mitochondria size, foamy cytoplasm, and glycogen accumulation in the liver of the periodontitis group compared with the control group. In addition, plasma levels of AlkP, high-density lipoprotein (HDL), triglycerides, and total cholesterol were also changed. CONCLUSION: Experimental periodontitis caused immunohistochemistry, histopathologic, ultrastructural, oxidative, and biochemical changes in the liver of rats.

Moderate-intensity exercise and renin angiotensin system blockade improve the renovascular hypertension (2K1C)-induced gastric dysmotility in rats.

Actually, arterial hypertension is a major public health concern, which involves the renin angiotensin aldosterone system (RAS), via activation of the angiotensin receptors AT1 and AT2 of the cardiovascular system. Although angiotensin is an important stimulant of the gut permeability to sodium and water, little is known about the effects of arterial hypertension on gut motor behavior. Thus, we evaluated in rats the effect of hypertension induced by two-kidney one-clip (2K1C) model on the gastric motility, as well as the influence of exercise and RAS blockers treatment in such phenomenon. One week after surgery the rats were treated with Aliskiren (50 mg·kg-1, p.o.), Captopril (50 mg·kg-1, p.o.) or Losartan (10 mg·kg-1, p.o). Other group of rats was submitted to swimming with 5% body weight overload. After 4 weeks of physical training or pharmacological treatment, we assessed the gastric retention in all groups (GR) of a liquid test meal, the mean arterial pressure (MAP), the heart rate (HR) and the HR variation (HRV) as well as the in vitro contractility of gastric fundus. Renovascular hypertension increased (p < 0.05) the GR, MAP and HR, a phenomenon prevented by pretreatment with RAS blockers or exercise. The two kidney one-clip Hypertension (2K1C) decreased (p < 0.05) the gastric fundus responsiveness, a phenomenon also prevented by exercise. It conclusion, renovascular hypertension delays the gastric emptying of liquids, a phenomenon involving the activation of RAS, where exercise or blockade with aliskiren, captopril and losartan prevent gastric dysmotility.

Garcinielliptone FC, a polyisoprenylated benzophenone from Platonia insignis Mart., promotes vasorelaxant effect on rat mesenteric artery.

Polyisoprenylated benzophenones represent a group of chemical compounds commonly identified in Clusiaceae species and are responsible for a large amount of biological activities. In this work, the vasorelaxant effect induced by garcinielliptone FC (GFC) isolated from Platonia insignis Mart. (Clusiaceae), a monotype species from Platonia genus, was investigated. GFC promoted an endothelium-independent vasorelaxation on phenylephrine (PHE, 10(-5) mol L(-1))-induced vasoconstriction, but not on KCl (80 mmol L(-1))-induced vasoconstriction, on rat superior mesenteric artery rings. In addition, a concentration-dependent decrease of PHE- or serotonin-induced cumulative concentration-response curves was observed for GFC, and a slight decrease of pD2 value on CaCl2-induced vasoconstriction. In a Ca(2+)-free medium, GFC interfered in calcium mobilisation from PHE (10(-5) mol L(-1))-sensitive intracellular stores. GFC-induced vasorelaxant effect is probably mediated by a dual effect on mobilisation of calcium intracellular stores and attenuation of transmembrane calcium influx.

Antihypertensive and vasorelaxant effects of ethanol extract of stem barks from Zanthoxylum rhoifolium Lam. in rats.

Administration of ethanol extract of stem bark from Z. rhoifolium (EEtOH-ZR) induced hypotension associated with a dual effect in heart rate in normotensive rats. This response was highlighted in spontaneously hypertensive rats (SHR). In rat superior mesenteric artery rings, the cumulative addition of EEtOH-ZR (0.1-750 microg/mL) on a phenylephrine-induced pre-contraction (10(-5) M) promoted a vasorelaxant effect by a concentration-dependent manner and independent of vascular endothelium. A similar effect was obtained on KCl-induced pre-contractions (80 mM). EEtOH-ZR attenuated contractions induced by cumulative addition of CaCl2 (10(-6)-3 x 10(-2) M) in depolarizing medium without Ca2+ only at 500 or 750 microg/mL. Likewise, on S-(-)-Bay K 8644-induced pre-contractions (10(-7) M), the EEtOH-ZR-induced vasorelaxant effect was attenuated. EEtOH-ZR (27, 81, 243 or 500 microg/mL) inhibited contractions induced by cumulative addition of phenylephrine (10(-9) - 10(-5) M) in endothelium-denuded preparations or by a single concentration (10(-5) M) in a Ca(2+)-free medium. The involvement of K+ channels was evaluated by tetraethylammonium (3 mM); the EEtOH-ZR-induced vasorelaxation was not attenuated. Thus, calcium influx blockade through voltage-operated calcium channels (CavL) and inhibition of calcium release from intracellular stores are probably underlying EEtOH-ZR-induced cardiovascular effects.

Citronellal, a monoterpene present in Java citronella oil, attenuates mechanical nociception response in mice.

CONTEXT: Citronellal is a monoterpene present in the oil of many species, including Cymbopogon winterianus Jowitt (Poaceae). OBJECTIVE: The present study investigated the effect of citronellal on inflammatory nociception induced by different stimuli and examined the involvement of the NO-cGMP-ATP-sensitive K⁺ channel pathway. MATERIALS AND METHODS: We used male Swiss mice (n = 6 per group) that were treated intraperitoneally with citronellal (25, 50 or 100 mg/kg) 0.5 h after the subplantar injection of 20 µl of carrageenan (CG; 300 µg/paw), tumor necrosis factor-α (TNF-α; 100 pg/paw), prostaglandin E2 (PGE2; 100 ng/paw) or dopamine (DA; 30 µg/paw). The mechanical nociception was evaluated at 0.5, 1, 2 and 3 h after the injection of the agents, using a digital analgesimeter (von Frey). The effects of citronellal were also evaluated in the presence of L-NAME (30 mg/kg) or glibenclamide (5 mg/kg). RESULTS: At all times, citronellal in all doses inhibited the development of mechanical nociception induced by CG (p < 0.001 and p < 0.01) and TNF-α (p < 0.001, p < 0.01, and p < 0.05). The citronellal was able to increase the pain threshold in the DA test (p < 0.001, p < 0.01, and p < 0.05) and in the PGE2 test at all times (p < 0.001 and p < 0.05). L-NAME and glibenclamide reversed the antinociceptive effects of the citronellal at higher doses in the PGE2 test. DISCUSSION AND CONCLUSION: These data suggest that citronellal attenuated mechanical nociception, mediated in part by the NO-cGMP-ATP-sensitive K⁺ channel pathway.

Calcium channel blockade as a target for the cardiovascular effects induced by the 8 (17), 12E, 14-labdatrien-18-oic acid (labdane-302).

The cardiovascular effects induced by labdane-302, a diterpene isolated from the stems of Xylopia langsdorffianna St. Hill and Tull, were evaluated in male Wistar rats. In normotensive, conscious animals, labdane-302 produced dose-dependent hypotension and tachycardia. These effects were significantly attenuated after pre-treatment with L-NAME (20 mg/kg, i.v.). In isolated mesenteric artery rings, labdane-302 (10(-10)-10(-4)M) elicited concentration-dependent relaxation of phenylephrine-induced contractions (IC50 = 5.4 +/- 1.4 microM). Endothelium removal, and pre-treatment with L-NAME (100 microM) or indomethacin (10 microM) caused significant reductions in sensitivity. Labdane-302 also caused concentration-dependent relaxation in arterial rings pre-contracted with high extracellular KCl (80 mM). In Ca2+-free depolarized preparations, labdane-302 inhibited contractions produced by cumulative increases in extracellular Ca2+ concentration. In GH3 cells, labdane-302 (100 microM) inhibited whole-cell L-type Ca2+ currents by approximately 50%. These results demonstrate that labdane-302 causes hypotension through peripheral vasodilation, mediated in part by NO and PGI2 and by blockade of Ca2+ entry through L-type Ca2+ channels.