Hind limb ischemic preconditioning induces an anti-inflammatory response by remote organs in rats

Ischemic preconditioning (IPC), a strategy used to attenuate ischemia-reperfusion injury, consists of brief ischemic periods, each followed by reperfusion, prior to a sustained ischemic insult. The purpose of the present study was to evaluate the local and systemic anti-inflammatory effects of hind limb IPC in male Wistar rat (200-250 g) models of acute inflammation. IPC was induced with right hind limb ischemia for 10 min by placing an elastic rubber band tourniquet on the proximal part of the limb followed by 30 min of reperfusion. Groups (N = 6-8) were submitted to right or left paw edema (PE) with carrageenan (100 µg) or Dextran (200 µg), hemorrhagic cystitis with ifosfamide (200 mg/kg, ip) or gastric injury (GI) with indomethacin (20 mg/kg, vo). Controls received similar treatments, without IPC (Sham-IPC). PE is reported as variation of paw volume (mL), vesical edema (VE) as vesical wet weight (mg), vascular permeability (VP) with Evans blue extravasation (µg), GI with the gastric lesion index (GLI; total length of all erosions, mm), and neutrophil migration (NM) from myeloperoxidase activity. The statistical significance (P < 0.05) was determined by ANOVA, followed by the Tukey test. Carrageenan or Dextran-induced PE and VP in either paw were reduced by IPC (42-58.7 percent). IPC inhibited VE (38.8 percent) and VP (54 percent) in ifosfamide-induced hemorrhagic cystitis. GI and NM induced by indomethacin were inhibited by IPC (GLI: 90.3 percent; NM: 64 percent). This study shows for the first time that IPC produces local and systemic anti-inflammatory effects in models of acute inflammation other than ischemia-reperfusion injury.

Participation of TNF-Ó and IL-1 in the pathogenesis of cyclophosphamide-induced hemorrhagic cystitis

The involvement of cytokines TNF-Ó and IL-1 has been investigated in a model of cyclophosphamide (CYP) - induced hemorrhagic cystitis. Male Swiss mice (25-30 g) received CYP in a single ip dose of 100, 200 or 400 mg/kg and were sacrificed 6, 12, 24, 48 and 72 h later. Cystitis was evaluated by determining the changes in bladder wet weight (BW) and plasma protein extravasation (PPE, measured by the Evans blue leakage technique). CYP treatment induced a marked increase in BW and in PPE, which was significant within 6 h and reached maximal values within 12 h (BW, 118 percent, P<0.05; N = 11; and PPE, 824 percent, P<0.05; N = 11), continuing to be significant until 48 h. Pretreatment of animals with whole anti-TNF-Ó serum (25 or 50 µl diluted in 500 µl 0.9 percent saline, ip, 30 min earlier caused a significant reduction in the CYP-induced BW increase in 6-h and 12-h cystitis (82 percent and 91 percent, respectively, P<0.05; N = 6) and...