Karoline S. Aragão

Phytol, a diterpene alcohol, inhibits the inflammatory response by reducing cytokine production and oxidative stress

Studies have shown that diterpenes have anti‐inflammatory and redox‐protective pharmacological activities. The present study aimed to investigate the anti‐inflammatory properties of phytol, a diterpene alcohol, in a mouse model of acute inflammation, and phytol effect on leukocyte recruitment, cytokines levels, and oxidative stress. The anti‐inflammatory activities of phytol were assessed by measuring paw edema induced by different inflammatory agents (e.g., λ‐carrageenan, compound 48/80, histamine, serotonin, bradykinin, and prostaglandin E2 [PGE2]), myeloperoxidase (MPO) activity, peritonitis model and cytokine levels. Further, oxidative stress was evaluated by determining glutathione (GSH) levels and malondialdehyde (MDA) concentration. The results showed that phytol (7.5, 25, 50, and 75 mg/kg) significantly reduced carrageenan‐induced paw edema, in a dose‐dependent manner. In addition, phytol (75 mg/kg) inhibited compound 48/80‐, histamine‐, serotonin‐, bradykinin‐ and PGE2‐induced paw edema. It also inhibited the recruitment of total leukocytes and neutrophils; decreased MPO activity, tumor necrosis factor‐α (TNF‐α) and interleukin‐1β (IL‐1β) levels, and MDA concentration; and increased GSH levels during carrageenan‐induced acute inflammation. These results suggest that phytol attenuates the inflammatory response by inhibiting neutrophil migration that is partly caused by reduction in IL‐1β and TNF‐α levels and oxidative stress.

Anti‐inflammatory and antimicrobial effect of lectin from Lonchocarpus sericeus seeds in an experimental rat model of infectious peritonitis

We have investigated the anti‐inflammatory and antimicrobial effect of the lectin from Lonchocarpus sericeus seeds (LSL) in a model of infectious peritonitis in adult Wistar rats. Animals were treated with saline or LSL (10mg kg−1, i.v) immediately and 6h after the induction of peritonitis via cecal ligation and single puncture. Twelve hours after surgery, animals were killed and the infectious process was monitored by total and differential count of cells from blood and peritoneal washing liquid, adenosine deaminase activity, antibiogram and the number of viable bacteria of the peritoneal cavity. LSL treatment decreased the inflammatory response evoked by the induction of peritonitis, as seen by the inhibition of neutrophil migration into peritoneal cavities, leucocytosis and reduction of adenosine deaminase activity in the peritoneal fluid. All these effects were reversed by the lectin association to N‐acetyl‐glucosamine. LSL in‐vitro did not show any antimicrobial action, but promoted a marked decrease of the viable bacterial population in peritoneal cavities. In conclusion, LSL inhibited the inflammatory response and the bacterial colonization of infectious peritonitis in rats.

Effect of telmisartan on levels of IL-1, TNF-α, down-regulated COX-2, MMP-2, MMP-9 and RANKL/RANK in an experimental periodontitis model.

Aim The aim of this study was to evaluate the effect of telmisartan (TELM) on inflammation, oxidation and the expression of matrix metalloproteinases (MMPs) and the expression RANKL/RANK/OPG in the periodontal tissue of a rat model for ligature-induced periodontitis. Materials and methods Male Wistar albino rats were randomly divided into five groups of 10 rats each: (i) non-ligated, given water; (ii) ligated, given water; (iii) ligated, given 1 mg/kg TELM; (iv) ligated, given 5 mg/kg TELM; and (v) ligated, given 10 mg/kg TELM. All groups were treated with saline or TELM for 10 days. Periodontal tissue was analysed by histopathology; by the immunohistochemical examination of COX-2, MMP-2, MMP-9 and the RANKL/RANK/OPG pathway; and by ELISA analysis of the levels of IL-1β, IL-10, TNF-α, myeloperoxidase (MPO), malonaldehyde (MDA) and glutathione (GSH). Results Treatment with 10 mg/kg TELM resulted in reduced concentrations of MPO, MDA (p < 0.05) and the pro-inflammatory cytokine IL-1β (p < 0.05); reduced expression of MMP-2, MMP-9, RANK, RANKL and COX-2; and an increase in OPG. The levels of TNF-α were significantly reduced in all TELM-treated groups. Conclusions These findings confirm the involvement of TELM in reducing the inflammatory response, oxidative stress and bone loss in ligature-induced periodontitis in rats.

Antiinflammatory and antinociceptive effects in mice of a sulfated polysaccharide fraction extracted from the marine red algae Gracilaria caudata

Many algal species contain relatively high concentrations of polysaccharide substances, a number of which have been shown to have anti-inflammatory and/or immunomodulatory activity. In this study, we evaluated the anti-inflammatory and antinociceptive effects in mice of a sulfated polysaccharide fraction (PLS) extracted from the algae Gracilaria caudata. The antiinflammatory activity of PLS was evaluated using several inflammatory agents (carrageenan, dextran, bradykinin, and histamine) to induce paw edema and peritonitis in Swiss mice. Samples of the paw tissue and peritoneal fluid were removed to determine myeloperoxidase (MPO) activity or TNF-α and IL-1β levels, respectively. Mechanical hypernociception was induced by subcutaneous injection of carrageenan into the plantar surface of the paw. Pretreatment of mice by intraperitoneal administration of PLS (2.5, 5, and 10 mg/kg) significantly and dose-dependently reduced carrageenan-induced paw edema (p < 0.05) compared to vehicle-treated mice. Similarly, PLS 10 mg/kg effectively inhibited edema induced by dextran and histamine; however, edema induced by bradykinin was unaffected by PLS. PLS 10 mg/kg inhibited total and differential peritoneal leukocyte counts following carrageenan-induced peritonitis. Furthermore, PLS reduced carrageenan-increased MPO activity in paws and reduced cytokine levels in the peritoneal cavity. Finally PLS pretreatment also reduced hypernociception 3–4 h after carrageenan. We conclude that PLS reduces the inflammatory response and hypernociception in mice by reducing neutrophil migration and cytokines concentration.

Anti-inflammatory and antinociceptive activity of epiisopiloturine, an imidazole alkaloid isolated from Pilocarpus microphyllus.

The aim of this study was to investigate the antinociceptive and anti-inflammatory activities of epiisopiloturine (1), an imidazole alkaloid found in the leaves of Pilocarpus microphyllus. The anti-inflammatory activity of 1 was evaluated using several agents that induce paw edema and peritonitis in Swiss mice. Paw tissue and peritoneal fluid samples were obtained to determine myeloperoxidase (MPO) activity or tumor necrosis factor (TNF)-α and interleukin (IL)-1β levels. The antinociceptive activity was evaluated by acetic acid-induced writhing, the hot plate test, and pain induction using formalin. Compared to vehicle treatment, pretreatment with 1 (0.1, 0.3, and 1 mg/kg, ip) of mice significantly reduced carrageenan-induced paw edema (p < 0.05). Furthermore, compound 1 at a dose of 1 mg/kg effectively inhibited edema induced by dextran sulfate, serotonin, and bradykinin, but had no effect on histamine-induced edema. The administration of 1 (1 mg/kg) following carrageenan-induced peritonitis reduced total and differential peritoneal leukocyte counts and also carrageenan-induced paw MPO activity and TNF-α and IL-1β levels in the peritoneal cavity. Pretreatment with 1 also reduced acetic acid-induced writhing and inhibited the first and second phases of the formalin test, but did not alter response latency in the hot plate test. Pretreatment with naloxone reversed the antinociceptive effect of 1.

Vatairea macrocarpa lectin induces paw edema with leukocyte infiltration.

A lectin from Vatairea macrocarpa (Vmac) seeds was investigated in a model of paw edema in rats and the possible involvement of leukocytes. Vmac (200 and 400 microg/paw, s.c.) induced a significant time- and dose-dependent paw edema, with leukocyte infiltration, which was drastically reduced in leukopaenic animals. These data suggest a pro-inflammatory effect for this lectin that is dependent on the presence of leukocytes.

Anti-inflammatory effect of a sulphated polysaccharide fraction extracted from the red algae Hypnea musciformis via the suppression of neutrophil migration by the nitric oxide signalling pathway.

The aim of this study was to evaluate the anti‐inflammatory effect of a sulphated polysaccharide fraction (PLS) extracted from the alga Hypnea musciformis and investigate the possible involvement of the nitric oxide (NO) pathway in this effect.

Role of soluble guanylate cyclase activation in the gastroprotective effect of the HO-1/CO pathway against alendronate-induced gastric damage in rats

Our objective was to evaluate the role of soluble guanylate cyclase (sGC) activation in the gastroprotective effect of the HO-1/CO pathway against alendronate-induced gastric damage in rats. Rats were pretreated, once daily for 4 days, with saline, hemin (HO-1 inducer), or dimanganese decacarbonyl (DMDC, CO donor). Another group received zinc protoporphyrin IX (ZnPP IX, HO-1 antagonist) 1 h before hemin treatment or sGC inhibitor (ODQ) 30 min before hemin and DMDC treatment. After 30 min, gastric damage was induced by alendronate (30 mg/kg) by gavage. On the last day of treatment, 4 h after alendronate administration, the animals were killed. Gastric lesions were measured using a computer planimetry program, and gastric corpus pieces were assayed for malondialdehyde (MDA), glutathione (GSH), pro-inflammatory cytokines (tumor necrosis factor [TNF]-α and interleukin [IL]-1β), myeloperoxidase (MPO), or bilirubin. Another group was used to measure gastric mucus. HO-1 expression was determined after saline or alendronate administration by immunohistochemistry. Alendronate induced gastric damage, produced neutrophil accumulation, increased MDA levels and MPO activity, and reduced GSH and mucus in the gastric tissue. Alendronate also increased HO-1 immunoreactivity and the level of bilirubin in gastric mucosa. Pretreatment with hemin or DMDC reduced neutrophil infiltration and TNF-α, IL-1β, and MDA formation, and increased the levels of GSH and mucus in the gastric tissue. ODQ completely abolished the gastroprotective effect of hemin and DMDC and increased alendronate gastric damage. Our results suggest that the HO-1/CO pathway plays a protective role against alendronate-induced gastric damage through mechanisms that can be dependent on sGC activation.

Blockade of TRPA1 with HC-030031 attenuates visceral nociception by a mechanism independent of inflammatory resident cells, nitric oxide and the opioid system.

Some studies have shown a somatic nociceptive response due to the activation of transient receptor potential A1 channels (TRPA1), which is modulated by the TRPA1 antagonist HC‐030031. However, a few studies report the role of TRPA1 in visceral pain. Therefore, we investigated the participation of TRPA1 in visceral nociception and the involvement of nitric oxide, the opioid system and resident cells in the modulation of these channels.

The hydrogen sulfide donor, Lawesson's reagent, prevents alendronate-induced gastric damage in rats

Our objective was to investigate the protective effect of Lawessons reagent, an H2S donor, against alendronate (ALD)-induced gastric damage in rats. Rats were pretreated with saline or Lawessons reagent (3, 9, or 27 µmol/kg, po) once daily for 4 days. After 30 min, gastric damage was induced by ALD (30 mg/kg) administration by gavage. On the last day of treatment, the animals were killed 4 h after ALD administration. Gastric lesions were measured using a computer planimetry program, and gastric corpus pieces were assayed for malondialdehyde (MDA), glutathione (GSH), proinflammatory cytokines [tumor necrosis factor (TNF)-α and interleukin (IL)-1β], and myeloperoxidase (MPO). Other groups were pretreated with glibenclamide (5 mg/kg, ip) or with glibenclamide (5 mg/kg, ip)+diazoxide (3 mg/kg, ip). After 1 h, 27 µmol/kg Lawessons reagent was administered. After 30 min, 30 mg/kg ALD was administered. ALD caused gastric damage (63.35±9.8 mm2); increased levels of TNF-α, IL-1β, and MDA (2311±302.3 pg/mL, 901.9±106.2 pg/mL, 121.1±4.3 nmol/g, respectively); increased MPO activity (26.1±3.8 U/mg); and reduced GSH levels (180.3±21.9 µg/g). ALD also increased cystathionine-γ-lyase immunoreactivity in the gastric mucosa. Pretreatment with Lawessons reagent (27 µmol/kg) attenuated ALD-mediated gastric damage (15.77±5.3 mm2); reduced TNF-α, IL-1β, and MDA formation (1502±150.2 pg/mL, 632.3±43.4 pg/mL, 78.4±7.6 nmol/g, respectively); lowered MPO activity (11.7±2.8 U/mg); and increased the level of GSH in the gastric tissue (397.9±40.2 µg/g). Glibenclamide alone reversed the gastric protective effect of Lawessons reagent. However, glibenclamide plus diazoxide did not alter the effects of Lawessons reagent. Our results suggest that Lawessons reagent plays a protective role against ALD-induced gastric damage through mechanisms that depend at least in part on activation of ATP-sensitive potassium (KATP) channels.