The effect of the chronic and acute antioxidant tempol (superoxide dismutase mimetic) treatment on cardiac ischemic tolerance was investigated in adult male Wistar rats. The first experimental group was given tempol (1 mM) in drinking water for three weeks, the second group received tempol (100 mg/kg, i.v.) 10 min before test ischemia, and control rats received the same volume of solvent. Anesthetized open-chest animals (pentobarbitone 60 mg/kg, i.p.) were subjected to 20-min coronary artery occlusion and 3-h reperfusion for infarct size determination. Ventricular arrhythmias were monitored during ischemia and at the beginning (5 min) of reperfusion. Acute tempol administration shifted the time profile of ischemic arrhythmias to the later phase and significantly increased the number of ischemic and reperfusion premature ventricular complexes, respectively (504±127 and 84±21) as compared with the chronically treated group (218±36 and 47±7) or controls (197±26 and 31±7). Acute tempol-treated rats exhibited a tendency to decrease infarct size (P = 0.087). The mechanism of proarrhythmic tempol action during ischemia and reperfusion remains to be elucidated., J. Neckář, B. Ošťádal, F. Kolář., and Obsahuje bibliografii a bibliografické odkazy
Obstructive sleep apnea (OSA) has been demonstrated to be
implicated in disorder of insulin secretion and diabetes mellitus.
In this study, we aimed to evaluate the protective role of tempol,
a powerful antioxidant, in chronic intermittent hypoxia
(IH)-induced pancreatic injury. The rat model of OSA was
established by IH exposure. The pathological changes, increased
blood-glucose level, and raised proinsulin/insulin ratio in
pancreatic tissues of rats received IH were effectively relieved
by tempol delivery. In addition, the enhanced levels of
pro-inflammatory cytokines, TNF-α, IL-1β, IL-6, and inflammatory
mediators, PGE2, cyclooxygenase-2 (COX-2), NO, and inducible
nitric oxide synthase (iNOS) in pancreatic tissue were suppressed
by tempol. Moreover, tempol inhibited IH-induced apoptosis in
pancreatic tissue as evidenced by upregulated Bcl-2 level, and
downregulated Bax and cleaved caspase-3 levels. Finally, the
abnormal activation of mitogen-activated protein kinase (MAPK)
and nuclear factor kappa-light-chain-enhancer of activated B cells
(NF-κB) signaling pathways induced by IH was restrained by
tempol administration. In summary, our study demonstrates that
tempol relieves IH-induced pancreatic injury by inhibiting
inflammatory response and apoptosis, which provides theoretical
basis for tempol as an effective treatment for OSA-induced
pancreatic injury.