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ABSTRACT Purpose Quantify the tissue content of metalloproteinase-9 (MMP-9) and collagen in colic mucosa with and without intestinal transit after infliximab administration in rats subjected to Hartmann's surgery. Methods Twenty-two rats underwent colon diversion by Hartmann's surgery. Animals were maintained with intestinal bypass for 12 weeks to induce development of diversion colitis (DC). Afterwards, animals were divided into three groups: first group received subcutaneous application of saline solution (SS) 0.9%, while the remaining two groups received infliximab subcutaneously at doses of 5 or 10 mg·kg-1·week-1 for five consecutive weeks. After the intervention, animals were sacrificed, removing the segments with and without intestinal transit. Diversion colitis was diagnosed by histological study, and its intensity was determined by a validated inflammatory scale. Tissue expression of MMP-9 was assessed byimmunohistochemistry, while total collagen was assessed by histochemistry. Tissue content of both was measuredby computerized morphometry. Results Colon segments without intestinal transit had a higher degree of inflammation, which improved in animals treated with infliximab. Collagen content was always lower in those without intestinal transit. There was an increase in the collagen content in the colon without transit in animals treated with infliximab, primarily at a dose of 10 mg·kg-1·week-1. There was an increase in the content of MMP-9 in the colon without fecal transit, and a reduction was observed in animals treated with infliximab, regardless of the dose used. Conclusions Application of infliximab reduces inflammation, increases the total collagen content and decreases the content of MMP-9 in the colon without intestinal transit.
Subject(s)
Animals , Rats , Colon/surgery , Intestinal Mucosa , Collagen , Rats, Wistar , Metalloproteases , InfliximabABSTRACT
Aims: The aim was to evaluate circulating levels of reactive oxygen species (ROS) and changes in central macular thickness (CMT) in patients with nonproliferative diabetic retinopathy (NPDR) after antioxidant supplementation. Materials and Methods: A total of 68 patients (68 eyes) with NPDR were enrolled. Patients were randomly divided into two groups: Treated with antioxidant supplement (Group A) and untreated control group (Group B). Each tablet, for oral administration, containing pycnogenol 50 mg, Vitamin E 30 mg and coenzyme Q10 20 mg. CMT and free oxygen radical test (FORT) were analyzed at baseline (T0), 3 (T1) and 6 (T2) months in both groups. Results: In Group A, FORT levels and CMT were significantly reduced over time (P < 0.001 for both). In Group B, FORT levels were increased (P < 0.001) and CMT did not vary significantly (P = 0.81) over 3 time points. Conclusions: This is the first study showing the reduction of ROS levels in patients with NPDR thanks to antioxidant therapy. Moreover, our findings have suggested also an influence on retinal thickness.
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BACKGROUND AND OBJECTIVES: To elucidate the mechanism of salicylate ototoxicity of free oxygen radicals (FORs), we made an animal model with Na-salicylate cochlear toxicity and evaluated the protective effect of free oxygen radical inhibitors. MATERIALS AND METHODS: Na-salicylate soaked in gelfoam was placed on the round window niche of guinea pigs for 2 hours. After removal of gelfoam, electrocochleography and evoked otoacoustic emission test were performed at regular time intervals. These tests were repeated to see the protective effect of FORs inhibitors after the injection of allopurinol or superoxide dismutase (SOD). RESULTS: Hearing loss was noted after removal of gelfoam which was soaked with Na-salicylate. After 6 hours, these ototoxicity effects disappeared. The OAE test showed similar response. FORs inhibitors showed protective effects and SOD was more effective than allopurinol. CONCLUSION: These results support the idea that FORs activity contributes to ototoxicity of Na-salicylate. This damage can be diminished by treatment with drugs that scavenge and inhibit the formation of FORs.
Subject(s)
Animals , Allopurinol , Audiometry, Evoked Response , Gelatin Sponge, Absorbable , Guinea Pigs , Guinea , Hearing Loss , Models, Animal , Oxygen , Reactive Oxygen Species , Superoxide DismutaseABSTRACT
The mechanism of salicylate ototoxicity appears to be multifactorial and decreased cochlear blood flow seems to play an important role. The purpose of the study was to assess an effect of allpurinol, a blocker of free oxygen radicals(FORs) formation, on salicylate ototxicity in guinea pig. ABR threshold shifts were observed in group 1, treated with salicylate(300mg/kg, IM) and group 2, pretreated with allopurinol(50mg/kg, PO, two times) before injection of salicylate(300mg/kg, IM). In group 1, significant ABR threshold shift was measured in 1 hour(p<0.05) and maximum threshold shift was noted in 2-3 hours, with complete recovery in 6 hours, after injection of salicylate. In group 2, there was a little ABR threshold shift through 6 hours after injection of salicylate, except average 5dB shift in 4 hours. ABR threshold shift was significantly greater in group 1 than in group 2, after injection of salicylate(p<0.05). With above result, allopurinol, a blocker of FORs formation, could attenuated the hearing loss after the administration of salicylate in guinea pig, and FORs might play a role in salicylateinduced hearing loss.
Subject(s)
Animals , Allopurinol , Guinea Pigs , Guinea , Hearing Loss , OxygenABSTRACT
AIM: To investigate the effects of angiotensin converting enzyme inhibitor (ACEI), benazepril(B), on cardiac function, free oxygen radicals, sarcoplasmic reticulum(SR) Ca~(2+)-ATPase following ischemia-reper-fusion in sportaneously hypertensive rats (SHRs). METHODS: Thirty 10-week-old female SHRs were randomly assigned into two groups: group SHR was control; The animal in group SHR+B was given with 10 mg/kg of benazepril perday. Another 15 Wistar rats with the same age and sex were normal control (group Wistar). After 12 weeks of pretreatment, all rats in each group were subjected to 30 min of left anterior descending coronary artery occlusion and 30 min of reperfusion. Hemodynamic parameters, left heart-to-body weight ratio(LVW/BW), myocardial malondialdehyde (MDA) concentration, superoxide dismutase (SOD) activity, and SR Ca~(2+)-ATPase activity were measured. RESULTS: Compared to group Wistar, the rats in group SHR had higher blood pressure, LVW/BW and myocardial MDA concentration, more serious left cardiac function injury and lower myocardial SOD activity and SR Ca~(2+)-ATPase activity; group SHR+B had lower myocardial MDA concentration, higher myocardial SOD activity, but no difference in blood pressure, LVW/BW, the degree of left cardiac function injury and myocardial SR Ca~(2+)-ATPase activity. CONCLUSION: Benazepril can attenuate ischemia-reperfusion-induced cardiac function injury by regression of left ventricular hypertrophy (LVH), improving SR Ca~(2+)-ATPase activity and decreasing oxygen free radicals injury in SHRs.