Purpose: We aimed to investigate the effects of methylene blue (MB) on NO production, myeloperoxidase (MPO) activity, antioxidant status and lipid peroxidation in lung injury during different stages of sepsis in rats. Material and Methods: Rats were randomly divided into 4 groups (n = 20): group C, sham operated; group CMB, sham operated and receiving MB (25 mg/kg, i.p.); group S, sepsis; group SMB, sepsis and receiving MB (25 mg/kg, i.p.). Sepsis was induced by cecal ligation and puncture (CLP). The MB dose was administered after CLP. Each group was subdivided into two subgroups (n = 10) which were sacrificed at 9 or 18 h after the surgical procedure. The levels of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX) and MPO activity, total nitrite/nitrate and malondialdehyde (MDA) in the lung tissue were measured. Lung injury was graded from 1 (injury to 25% of the field) to 4 (diffuse injury) by the pathologist. Results: In group SMB, while SOD and CAT increased in both early and late sepsis periods, GSH-PX increased significantly only in the early sepsis period when compared with group S. Increase in lung MPO activity after CLP-induced sepsis was prevented by MB administration. MB significantly decreased to nitrite/nitrate and MDA levels both in early and late sepsis periods when compared with group S (p < 0.05). Group S showed a marked increase in neutrophil infiltration into the interstitial space and thickening of the alveolar septa, whereas the alveolar damage score was lower in the SMB group (p < 0.05). Conclusion: MB reduced the MPO activity and lipid peroxidation by both decreasing oxidative stress and NO overproduction in the lungs, which resulted in the attenuation of lung injury after CLP-induced sepsis in rats.
Objectives We investigated acupuncture, a potential contributor for burn-care, on physiological and pathological pain mechanisms and systemic and local inflammatory responses in a rat experimental burn model. Methods Forty male Sprague-Dawley rats were divided into 2 groups. One-hour groups(5 rats/group) were observed for 1 hour and included Sh1(sham/observation), ShA1(sham+acupuncture/observation), Brn1(burn/observation), and BrnA1(burn+acupuncture/observation). Seven-day groups(5 rats/group) were observed for 7 days and included Sh7(sham/observation), ShA7(sham+acupuncture/observation), Brn7(burn/observation), and BrnA7(burn+acupuncture/observation). “Pain-distress scores” were noted daily, acupuncture was repeated within every wound-dressing change on alternate days. After observation periods, blood samples for interleukin-6 and beta-endorphin and skin biopsies for inflammatory-changes and immunohistochemical-staining of interleukin-6 were collected for analysis( P< .05 ). Results In 1-hour groups, interleukin-6 accumulation in burn wounds of BrnA1 was less than Brn1, with Brn1 having the highest mean blood level(P< .05). Mean beta-endorphin levels were higher in ShA1, Brn1, and BrnA1 than in Sh1(P< .05). In all 7-day groups, the agonizing period was 48 to72 hours after burn, with Brn7 most affected(P< .05). Microvessels were multiplied in Brn7group, with significantly higher numbers in burn wounds of BrnA7(P˂ .05). Burn wounds of BrnA7 had less accumulation of interleukin-6 than Brn7 with Brn7-group having the highest mean blood level and Sh7, ShA7, and BrnA7 having similarly low levels(P˃ .05). Beta-endorphin levels in ShA7, Brn7, and BrnA7 were lower than in Sh7(P< .05). Conclusions Acupuncture contributed to management of physiological and pathological pain, modulation of inflammatory responses, and associated enhancement of angiogenesis in acute phase of burn injury in rats.
The role of metformin in the management of polycystic ovary syndrome (PCOS) and PCOS-related obesity remains controversial. Recent research on the treatment of PCOS-related obesity investigated novel therapeutic agents with the potential to work synergistically with metformin. The aim of the present study was to determine the synergistic effect of a phosphodiesterase 4 inhibitor (PDE4i) and metformin on weight and hormonal changes in a rat model of PCOS. A total of 40 female Sprague-Dawley rats were randomly divided into 4 groups (n=10/group): Sham; PCOS control (no medication after PCOS induction with dehydroepiandrosterone); metformin (300 mg/kg/day p.o. after PCOS induction); and metformin + PDE4i (300 mg/kg/day p.o. metformin + 0.5 mg/kg/day p.o. PDE4i after PCOS induction). The body weight was measured every 7 days, from day 1 to day 49. Vaginal smears were performed and examined daily via light microscopy for determination of the stage of each rat's estrous cycle. At the end of 21st day and at the end of the study, blood samples were collected from rats and the testosterone and insulin levels were measured. Immunohistochemical staining was performed to quantify phosphorylated cyclic AMP response element-binding protein expression in all groups. At the end of the study, the median body weight differed significantly among the groups (χ 2 =30.581, P<0.001), being the highest in the PCOS control group and the lowest in the metformin + PDE4i group. At the end of the study, the median testosterone level differed significantly among the groups (χ 2 =27.057, P<0.001), being the highest in the PCOS control group and the lowest in the metformin + PDE4i group. The cycle was restored to normal at the end of the study in all the rats in the metformin and metformin + PDE4i groups, whereas an irregular cycle persisted in all the rats in the PCOS control group. In conclusion, PDE4i + metformin was superior to metformin alone in reducing weight gain and decreasing the testosterone levels in a rat model of PCOS.
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