We investigated the potential protective effects of montelukast (MLK) on cecal ligation and puncture (CLP)–induced tissue injury in vital organs — liver, heart, kidneys, and especially lungs — through inhibition of the proinflammatory cytokine response and the generation of reactive oxygen species (ROS) in rats. The rat groups were (1) a 10-mg/kg MLK-treated CLP group; (2) a 20-mg/kg MLK-treated CLP group; (3) a 20-mg/kg MLK-treated, sham-operated group; (4) a CLP control group; and (5) a sham-operated control group. MLK treatment significantly decreased proinflammatory (tumor necrosis factor-alpha, interleukin-6) cytokine levels following CLP. The lipid peroxide level increased in the lung, heart, liver, and kidney tissues after CLP-induced sepsis, and myeloperoxidase activity increased in the lung, heart, and liver tissues. MLK attenuated this elevation in all tissues except the kidney, dose dependently. The glutathione levels and superoxide dismutase activity were significantly increased in the lung, liver, and kidney tissues after MLK treatment. MLK treatment after CLP also potentially reduced mortality. The lung and kidney tissues were the most protected by MLK under sepsis conditions. We can suggest that MLK reverses the systemic inflammatory reaction to polymicrobial sepsis and thereby reduces multiple organ failure.
a-Lipoic acid (ALA) has been termed the 'ideal' antioxidant, a readily absorbed and bioavailable compound capable of scavenging a number of free radicals, and it has been used for treating diseases in which oxidative stress plays a major role. The present study was designed to gain a better understanding for the positive effects of ALA on the models of acute and chronic inflammation in rats, and also determine its anti-oxidative potency. In an acute model, three doses of ALA (50, 100 and 200 mg/kg) and one dose of indomethacin (25 mg/kg) or diclofenac (25 mg/kg) were administered to rats by oral administration. The paw volumes of the animals were calculated plethysmometrically, and 0·1 ml of 1 % carrageenan (CAR) was injected into the hind paw of each animal 1 h after oral drug administration. The change in paw volume was detected as five replicates every 60 min by plethysmometry. In particular, we investigated the activities of catalase, superoxide dismutase (SOD), glutathione S-transferase (GST), glutathione peroxidase (GPx), glutathione reductase (GR), inducible NO synthase (iNOS) and myeloperoxidase (MPx), and the amounts of lipid peroxidation (LPO) or total GSH in the paw tissues of CAR-injected rats. We showed that ALA exhibited anti-inflammatory effects on both acute and chronic inflammations, and a strongly anti-oxidative potency on linoleic acid oxidation. Moreover, the administration of CAR induced oedema in the paws. ALA significantly inhibited the ability of CAR to induce: (1) the degree of acute inflammation, (2) the rise in MPx activity, (3) the increases of GST and iNOS activities and the amount of LPO and (4) the decreases of GPx, GR and SOD activities and the amount of GSH. In conclusion, these results suggest that the anti-inflammatory properties of ALA, which has a strong anti-oxidative potency, could be related to its positive effects on the antioxidant system in a variety of tissues in rats.
SummarySepsis is a systemic inflammatory response to infection and a major cause of morbidity and mortality. Sildenafil (SLD) is a selective and potent inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase PDE5. We aimed to investigate the protective effects of sildenafil on caecal ligation and puncture (CLP)-induced sepsis in rats. Four groups of rats were used, each composed of 10 rats: (i) 10 mg/kg SLD-treated CLP group; (ii) 20 mg/kg SLD-treated CLP group; (iii) CLP group; and (iv) sham-operated control group. A CLP polymicrobial sepsis model was applied to the rats. All groups were killed 16 h later, and lung, kidney and blood samples were analysed histopathologically and biochemically. Sildenafil increased glutathione (GSH) and decreased the activation of myeloperoxidase (MPO) and of lipid peroxidase (LPO) and levels of superoxide dismutase (SOD) in the septic rats. We observed a significant decrease in LPO and MPO and a decrease in SOD activity in the sildenafil-treated CLP rats compared with the sham group. In addition, 20 mg/kg sildenafil treatment in the sham-operated rats improved the biochemical status of lungs and kidneys. Histopathological analysis revealed significant differences in inflammation scores between the sepsis group and the other groups, except the CLP + sildenafil 10 mg/kg group. The CLP + sildenafil 20 mg/kg group had the lowest inflammation score. Sildenafil treatment decreased the serum tumour necrosis factor (TNF)-a level when compared to the CLP group. Our results indicate that sildenafil is a highly protective agent in preventing lung and kidney damage caused by CLPinduced sepsis via maintenance of the oxidant-anti-oxidant status and decrease in the level of TNF-a.
The possible role ofβ-2 adrenergic receptors in modulation of inflammatory and nociceptive conditions suggests that theβ-2 adrenergic receptor agonist, salbutamol, may have beneficial anti-inflammatory and analgesic effects. Therefore, in this study, we induced inflammatory and nociceptive responses with carrageenan-induced paw edema or cotton-pellet-induced granuloma models, both of which result in oxidative stress. We hypothesized that salbutamol would prevent inflammatory and nociceptive responses by stimulatingβ-2 adrenergic receptors and the prevention of generation of ROS during the acute inflammation process in rats. Both doses of salbutamol used in the study (1 and 2 mg/kg) effectively blocked the acute inflammation and inflammatory nociception induced by carrageenan. In the cotton-pellet-induced granuloma test, both doses of salbutamol also significantly decreased the weight of granuloma tissue on the cotton pellets when compared to the control. Anti-inflammatory and analgesic effects of salbutamol were found to be comparable with those of indomethacin. Salbutamol decreased myeloperoxidase (MPO) activity and lipid peroxidation (LPO) level and increased the activity of superoxide dismutase (SOD) and level of glutathione (GSH) during the acute phase of inflammation. In conclusion, salbutamol can decrease acute and chronic inflammation, possibly through the stimulation ofβ-2 adrenergic receptors. This anti-inflammatory effect may be of significance in asthma treatment, where inflammation also takes part in the etiopathology. This study reveals that salbutamol has significant antioxidative effects, which at least partially explain its anti-inflammatory capabilities. These findings presented here may also shed light on the roles ofβ-2 adrenergic receptors in inflammatory and hyperalgesic conditions.
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