Leukocytic ·O 2 − and cardiac dysfunctions in isolated perfused rat hearts

Abstract

Superoxide radicals are supposed to contribute to myocardial reperfusion injury. Their origin, however, is still a matter of debate. Polymorphonuclear leukocytes (PMNL) have been discussed as a major postischaemic .O2- source [Lucchesi and Mullane (1986) Ann Rev Pharmacol Toxicol 26: 201-224]. We studied the role of .O2- derived from human polymorphonuclear leukocytes in reperfused and normoxic perfused isolated rat hearts. During reperfusion PMNL exerted deleterious effects on different parameters (e.g. contractility, coronary flow) of isolated rat hearts. Under normoxic perfusion conditions stimulation of PMNL with N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP) caused bradycardia and a transient vasoconstriction. Superoxide dismutase (SOD) administration did not influence any of the PMNL effects mentioned, suggesting that leukocytic .O2- was not involved in PMNL-induced cardiac dysfunctions.

Activation of renal haeme oxygenase-1 alleviates gentamicin-induced acute nephrotoxicity in rats

“…Previous reports have shown that gentamicin renal injury is mediated via generation of ROS resulting in severe tissue damage . Under normal conditions ROS, which are generated due to cellular functions, are eliminated by intrinsic antioxidant enzyme systems (SOD, catalase and GSH) .…”

“…[29] Previous reports have shown that gentamicin renal injury is mediated via generation of ROS resulting in severe tissue damage. [30,31] Under normal conditions ROS, which are generated due to cellular functions, are eliminated by intrinsic antioxidant enzyme systems (SOD, catalase and GSH). [31] It is noteworthy that HO-1, the rate-limiting enzyme in haeme catabolism, is essential in protecting various body tissues against oxidative stress and inflammatory injury.…”

“…[30,31] Under normal conditions ROS, which are generated due to cellular functions, are eliminated by intrinsic antioxidant enzyme systems (SOD, catalase and GSH). [31] It is noteworthy that HO-1, the rate-limiting enzyme in haeme catabolism, is essential in protecting various body tissues against oxidative stress and inflammatory injury. [32,33] Induction of HO-1 by haemin catalyses oxidative degradation of haeme into CO, biliverdin and ferrous iron.…”

Rabbit polymorphonuclear leukocytes release a factor that causes constriction of the coronary vasculature

“…Several reports of vasoconstriction in isolated, perfused hearts do suggest that reactive oxygen species are mediators of constriction, particularly OH Ϫ , because thiourea (26) and dimethylurea (7) attenuate the decrease in PP. The superoxide anion is also implicated in some studies, because SOD can attenuate the constrictor effects (7); however, SOD has little effect on constrictor responses in other studies (6). We did not test the response to PMN supernatant in the presence of oxygen radical scavengers, because it is unlikely that reactive oxygen species could survive the storage procedures.…”