Oxidative stress and inflammation are differentially affected by atorvastatin, pravastatin, rosuvastatin, and simvastatin on lungs from mice exposed to cigarette smoke.

Our aim was to investigate the effects of four different statins on acute lung inflammation induced by cigarette smoke (CS). C57BL/6 male mice were divided into a control group (sham-smoked) and mice exposed to CS from 12 cigarettes/day for 5 days. Mice exposed to CS were grouped and treated with vehicle (i.p.), atorvastatin (10 mg/kg), pravastatin (10 mg/kg), rosuvastatin (5 mg/kg), or simvastatin (20 mg/kg). Treatment with statins differentially improved the pulmonary response when compared to the CS group. Atorvastatin and pravastatin demonstrated slightly effects on inflammation and oxidative stress. Rosuvastatin demonstrated the best anti-inflammatory effect, whereas simvastatin demonstrated the best antioxidant response.

Oxidative damage in alveolar macrophages exposed to cigarette smoke extract and participation of nitric oxide in redox balance.

Nitric oxide (NO) acts in both pathological and biological processes. We investigated the role of NO in the regulation of cigarette smoke-induced oxidative stress in rat alveolar macrophages (RAM). RAM collected from Wistar rats were cultured in 5% concentration cigarette smoke extract (CSE) for 1h. RAM exposed to CSE were then co-incubated with L-NAME (LN), L-arginine (LA), N-acetylcysteine (NAC) and both LN and NAC. RAM cultured only with medium was considered as control group. Biochemical analysis were performed to measure cellular metabolism (MTT), nitrite levels, superoxide dismutase (SOD) and glutathione peroxidase activities, reduced glutathione (GSH) and oxidized (GSSG), malondialdehyde and myeloperoxidase activity. During exposure to CSE, increased NO levels were not only associated with an increase of cell activation, but also affected MTT levels in RAM. CSE exposure resulted in significant redox imbalance in RAM. NAC administration affected SOD antioxidant profile regardless NO levels; however nitrite values were associated with GSH/GSSG ratio. In addition, lipid peroxidation appeared to be nitric-oxide dependent. Furthermore, the use of NAC significantly reduced the expression of NFkB normally observed in RAM exposed to CSE. The present results show that NO appeared to be involved in RAM activation, oxidative status maintenance and lipid peroxidation process during exposure to CSE.

L-NAME and L-arginine differentially ameliorate cigarette smoke-induced emphysema in mice.

Nitric oxide (NO) represents one of the most important intra- and extracellular mediators and takes part in both biologic and pathologic processes. This study aimed to verify the treatment with an NO inhibitor and an NO substrate in pulmonary emphysema induced by cigarette smoke (CS) in a murine model. We compared N-acetylcysteine (NAC), a precursor of glutathione, to G-nitro-L-arginine-methyl ester or L-NAME (LN), which is an NO inhibitor, and to l-arginine (LA), which is a substrate for NO formation. Mice were divided into several groups: control, CS, CS + LN, CS + LA, and CS + NAC. Control and CS groups were treated daily with a vehicle, while CS + LN, CS + LA, and CS + NAC groups were treated daily with LN (60 mg/kg), LA (120 mg/kg) and NAC (200 mg/kg), respectively. The bronchoalveolar lavage was analyzed and the lungs were removed for histological and biochemical analysis. CS increases neutrophil number. Neutrophil number was lowest in CS + LN, followed by CS + LA. The lungs of CS + LN, CS + LA and CS + NAC mice were protected compared to the lungs of CS mice, but not equal to the quality of lungs in control mice. The CS group also exhibited increased oxidative stress, which was also present in the CS + LN group and to a lesser extent in the CS + LA group. Tissue inhibitor of metalloproteinase 1 and 2 increased in the CS + LN group and to a lesser extent in the CS + LA group relative to the control group. These results suggest that LN and LA treatment protected the mouse lung from CS. However, NAC treatment was more than LN and LA. We suggest that the protection conferred by LN treatment requires a balance between proteases and antiproteases, and that protection conferred by LA treatment involves the balance between oxidants and antioxidants.

Organ-related cigarette smoke-induced oxidative stress is strain-dependent.

BACKGROUND: Cigarette smoke (CS) is associated with oxidative stress in several organs because it contains high concentrations of free radicals and reactive oxygen species. Experimental models, using different strains, provide important insights into the genetic basis of diseases. This study sought to identify, in different mouse strains, the organ that is most-susceptible to CS-induced oxidative stress to obtain an optimized experimental animal model of oxidative injury induced by CS. MATERIAL/METHODS: Male Swiss, DBA/2, C3H, BALB/c, and C57BL/6 mice were exposed to CS 3 times a day (4 cigarettes per session) for 60 consecutive days. Control groups from the same strains were sham-treated. Protein content, malondialdehyde level, myeloperoxidase activity, and nitrite level were assayed in lung, liver, kidney, and brain from all strains. Catalase and glutathione peroxidase activities were measured. Analyses of data were done by using a 1-way ANOVA with Bonferroni's post-test (P<.05). RESULTS: Cigarette smoke exposure resulted in distinct, organ-specific responses among strains. The survival rate of DBA/2 mice was lowest. BALB/c and C57BL/6 strains were more-susceptible to oxidative damage in the lung and liver. C3H and C57BL/6 mice were more-susceptible to oxidative damage in the brain. No renal oxidative damage was seen. CONCLUSIONS: Mouse strains and individual organs display a range of susceptibilities to CS-induced oxidative stress. BALB/c and C57BL/6 strains appear to be the best choices as experimental models for studying CS effects on liver and lung, and C3H and C57BL/6 strains for CS-effects on the brain.

Involvement of nitric oxide in acute lung inflammation induced by cigarette smoke in the mouse.

Short-term exposure to cigarette smoke (CS) leads to acute lung inflammation (ALI) by disturbing oxidant/antioxidant balance. Both CS exposure and lung inflammation are important risk factors in the pathogenesis of chronic obstructive pulmonary disease. Nitric oxide (NO) is an oxidant both present in CS and produced in the inflammatory response, but its role in the effects of CS exposure is unclear. Our aim was to study involvement of NO in a model of CS exposure. Groups of mice (male C57BL/6) exposed to CS (six cigarettes per day over five days) were simultaneously subjected to treatment with vehicle (CS), 60mg/kg/day omega-nitro-l-arginine methyl ester (CS+l-NAME), 20mg/kg/day nitroglycerine (CS+NTG), or 120mg/kg/day l-arginine (CS+l-arg). Bronchoalveolar lavage fluid was then aspirated to perform cell counts, and malondialdehyde (MDA), nitrite, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels were measured in lung homogenates. Macrophage and neutrophil counts were increased in the CS (p<0.001) and CS+l-NAME groups (p<0.05 and p<0.01, respectively); the CS+NTG and CS+l-arg groups showed no differences from the control group. MDA was increased in the CS (p<0.05) and CS+l-NAME (p<0.01) groups when compared to the control group. Nitrite levels were decreased in the CS and CS+l-NAME groups (p<0.001) and increased in the CS+NTG (p<0.001) and CS+l-arg (p<0.01) groups when compared to the control. CAT, SOD and GPx activities in the CS and CS+l-NAME groups were all significantly increased compared to the control group. Our results suggest that administration of NO donors or substrates may be a useful therapy in the treatment of ALI caused by CS.

Bone healing in rats submitted to weight-bearing and non-weight-bearing exercises.

BACKGROUND: To investigate the effects of low-intensity exercise on bone healing during a short time. MATERIAL/METHODS: We made a surgical 1-mm perforation in the upper third medial cortical of the right tibia of 45 male Wistar rats (3 months old; mean weight, 282+/-34 g). Animals were randomly assigned to a swimming exercise group (SWIM, n=15), a running exercise group (RUN, n=15), or a no exercise control group (CON, n=15). Treatment sessions (10 minutes/day, 5 days/week) were done for 7, 14, or 21 days. Tibias were removed for radiographic, morphometric, and stereologic analyses. Blood samples were obtained for biochemical analyses. RESULTS: Serum phosphorus levels were higher in animals in the RUN group compared with animals in the SWIM group on the seventh day. On the 14th day, the tibias of the animals in the SWIM and RUN groups exhibited higher radiopacity in radiographic grades than animals in the CON group. No difference in collagen morphometry was verified. On the 21st day, serum alkaline phosphatase levels were higher in animals in the CON group than they were in the exercise groups, and animals in the SWIM and CON groups demonstrated an increase in newly formed bone in comparison to animals in the RUN group. CONCLUSIONS: At the 14th day of treatment, weight-bearing exercise, assessed by radiography, was found to be beneficial for bone healing. Results at the 21st day of treatment further supported the benefits of non-weight-bearing exercises, showing that weight-bearing exercise may improve bone repair in rats.