Effects of diabetes on cytokines and oxidative organ injury in a rat model of sepsis.

We aimed to investigate how Diabetes Mellitus (DM) affects myeloperoxidase activity, antioxidant status, and lipid peroxidation using biochemical approaches in heart, liver, and lung and serum cytokine analyses, such as interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) in rat with sepsis induced by a cecal ligation and puncture-induced (CLP) sepsis. The rats were divided into four groups: control group, diabetic group, sepsis group, and diabetic+sepsis group. DM was induced in the male Wistar albino rats by administration of alloxan. Polymicrobial sepsis was induced by cecal ligation and two-hole puncture. After alloxan administration, all groups of rats were allowed to recover for 1 month. CLP model was applied after 1 month recovery to group 3 and 4. IL-6 and TNF-α, were measured. Effects of antioxidant defenses on the DM and/or sepsis process, the antioxidant levels superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) were evaluated in heart, lung and liver tissues. The oxidant levels, such as lipid peroxidation (LPO) and myeloperoxidase (MPO) levels were also evaluated in tissues. We demonstrated DM to augment the level of oxidant and proinflammatory cytokines in lung, liver, and heart and also to exacerbate oxidative injury as assessed by increased LPO and MPO, and decreased GSH and SOD levels in a sepsis model. DM increased levels of proinflammatory cytokines while DM also resulted in significantly increased levels of proinflammatory cytokines following CLP. DM-increased plasma proinflammatory cytokines levels correlated positively with tissue oxidant levels, such as MPO and LPO levels in a rat abdominal sepsis model, based on CLP, which resulted in the exacerbation of oxidative organs injury.

The role of oxidative stress in diabetic cardiomyopathy: an experimental study.

BACKGROUND: Diabetes mellitus (DM) has a negative effect on cardiovascular functions. Little, however, is known of the overall effect of DM on the cardiac histology or the pathophysiological basis of this. AIM: We aimed to investigate the role of oxidative stress on the pathogenesis of diabetic cardiomyopathy in an experimental model. MATERIALS AND METHODS: 12 week-old female Sprague Dawley rats were randomly allocated into a healthy control group (n=6) and an DM group (n=6). After 12 weeks of alloxan induced DM, the groups' cardiac tissues were histopathologically analyzed and examined for determination of oxidant and antioxidant enzymes [activities of catalase (CAT), superoxide dismutase (SOD), and myeloperoxidase (MPO) and amount of reduced glutathione (GSH) and lipid peroxidation (LPO)]. RESULTS: When compared to the control group, the DM group showed cardiomyopathic changes. In the DM group, activities of CAT (144 +/- 0.9 vs. 112 +/- 1.4, p < 0.05) and LPO amount (27.0 +/- 0.74 vs. 14.4 +/- 0, 20, p < 0.05) were significantly increased whereas activities of SOD (142 +/- 0.2 vs. 146 +/- 0.7, p < 0.05) and amount of GSH (3.48 +/- 0.01 vs. 3.73 +/- 0.01, p < 0.05) were significantly decreased when compared to the control group. Besides, activities of MPO (7.3 +/- 0.02 vs. 8.6 +/- 0.11, p < 0.05) were comparable between groups. CONCLUSIONS: Using the experimental animal model, we were able to demonstrate that DM causes cardiomyopathic changes, and we propose that these changes could be mediated by an oxidative stress.

Sildenafil treatment attenuates lung and kidney injury due to overproduction of oxidant activity in a rat model of sepsis: a biochemical and histopathological study.

Sepsis 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)-α 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 CLP-induced sepsis via maintenance of the oxidant-anti-oxidant status and decrease in the level of TNF-α.

Gastroprotective and antioxidant effects of amiodarone on indomethacin-induced gastric ulcers in rats.

Reactive oxygen species (ROS) have been implicated in the etiology of indomethacin-induced gastric mucosal damage. This study investigated amiodarone's protective effects against oxidative gastric mucosal damage induced by indomethacin. Amiodarone is a widely used antiarrhythmic agent. We have investigated alterations in the glutathione level, and the activities of antioxidative enzymes [superoxide dismutase, catalase, glutathione s-transferase glutathione reductase and myeloperoxidase], as markers for ulceration process following oral administration of amiodarone and ranitidine in rats with indomethacin-induced ulcers. In the present study we found that 1) amiodarone, lansoprazole and ranitidine reduced the development of indomethacin-induced gastric damages, at a greater magnitude for amiodarone and lansoprazole than for ranitidine; 2) amiodarone and ranitidine alleviated increases in the activities of catalase and glutathione s-transferase enzymes resulting from ulcers; 3) amiodarone and ranitidine ameliorated depressions in the glutathione level and the activities of superoxide dismutase and glutathione reductase enzymes caused by indomethacin administration; and 4) all doses of amiodarone amplified the myeloperoxidase activity resulting from indomethacin-induced gastric ulcers. The results indicate that the gastroprotective activity of amiodarone, which may be linked to its intrinsic antioxidant properties, cannot be attributed to its effect on myeloperoxidase activity.

The inhibition of gastric mucosal lesion, oxidative stress and neutrophil-infiltration in rats by the lichen constituent diffractaic acid.

The antiulcerogenic effect of diffractaic acid (DA) isolated from Usnea longissima, a lichen species, on indomethacin (IND)-induced gastric lesions was investigated in rats. Administration of 25, 50, 100 and 200 mg/kg doses of DA and ranitidine (RAN) (50 mg/kg dose) reduced the gastric lesions by 43.5%, 52.9%, 91.4%, 96.7% and 72.7%, respectively. It is known that oxidative stress leads to tissue injury in organisms. Thus, in all treated groups of rats, the in vivo activities of the antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and the levels of reduced glutathione (GSH) and lipid peroxidation (LPO) were evaluated. IND caused oxidative stress, which resulted in LPO in tissues, by decreasing the levels of GPx, SOD and GSH as compared to healthy rats. In contrast to IND, the administration of DA and RAN showed a significant decrease in LPO level and an increase in tissue SOD, GPx and GSH levels. However, while CAT activity was significantly increased by the administration of IND, the administration of DA and RAN decreased CAT activity. The administration of IND also increased the myeloperoxidase (MPx) activity, which shows neutrophil infiltration into the gastric mucosal tissues. In contrast to IND, the administration of DA and RAN decreased MPx activity. The changes in activities of gastric mucosal nitric oxide synthases (NOS) throughout the development of gastric mucosal damage induced by IND were also studied. A decrease in constitutive NOS (cNOS) activity and an increase in inducible NOS (iNOS) activity were determined in gastric damaged tissues induced by IND. The administration of DA (100 mg/kg dose) and RAN reversed the activities of iNOS and cNOS. These results suggest that the gastroprotective effect of DA can be attributed to its enhancing effects on antioxidant defense systems as well as reducing effects of neutrophil infiltration.

Effects of water extract of Usnea longissima on antioxidant enzyme activity and mucosal damage caused by indomethacin in rats.

In this study, the antiulcerogenic effect of a water extract obtained from the lichen species Usnea longissima was investigated using indomethacin-induced ulcer models in rats. Experimental groups consisted of six rats. Antiulcerogenic activities of 50, 100 and 200mg/kg body wt. doses of the water extract were determined by comparing the negative (treated only with indomethacin) and positive (ranitidine) control groups. Although all doses of the water extract of U. longissima showed significant antiulcerogenic activity as compared to negative control groups, the highest activity was observed with 100 mg/kg body wt. doses (79.8%). The water extract of U. longissima showed moderate antioxidant activity when compared with trolox and ascorbic acids used as positive antioxidants. In addition, the activities of antioxidant enzymes [superoxide dismutase (SOD), catalase (CAT) and glutathione S-transferase (GST)] were determined in the stomach tissues of rats and compared with those of the negative and positive control groups to expose the effects of antioxidant enzymes on antiulcerogenic activity. SOD and GST enzymes activities in indomethacin-administrated tissues were reduced significantly by indomethacin in comparison to control groups. These enzymes were activated, however, by the water extracts of U. longissima. In contrast to SOD and GST activities, CAT activity was increased by indomethacin and reduced by all doses of U. longissima and ranitidine. The present results indicate that the water extract of U. longissima has a protective effect in indomethacin-induced ulcers, which can be attributed to its antioxidant potential.

Antioxidant activity, reducing power and total phenolic content of some lichen species.

The total antioxidant activity, total phenolic content and reducing power of methanol and water extracts of four lichen species, Bryoria fuscescens, Dermatocarpon intestiniformis, Peltigera rufescens and Pseudevernia furfuracea, were determined in vitro. Water and methanol extracts of P. rufescens showed the highest antioxidant activity. However, there was no correlation between antioxidant activity and total phenolic content of the extracts. Although the methanol extract of P. furfuracea had the highest total phenolic contents, it exhibited low antioxidant activity. In contrast, there was a strong correlation between reducing power and total antioxidant activity of the extracts. The highest reducing power was determined for the methanol extract of P. rufescens.

Anti-inflammatory and antiulcerogenic effects of the aqueous extract of Lobaria pulmonaria (L.) Hoffm.

An aqeuous extract of Lobaria pulmonaria (L.) Hoffm., from which a tea is prepared and consumed as treatment for various diseases in northeastern Turkey, was tested for its anti-inflammatory and antiulcerogenic effects in rats. The carrageenan-induced paw edema, cotton pellet granuloma and indomethacin-induced gastric damage models were used to determine these effects. The extract exhibited moderate anti-inflammatory and strong antiulcerogenic activities.