Effects of phosphodiestrase type 5 inhibitors in epinephrine-induced arrhythmia in rats: Involvement of lactate dehydrogenase and creatine kinase downregulation and adiponectin expression.

Cardiac arrhythmia is a common cause of mortality, and its progression may be due to abnormal sympathetic nerve activity and catecholamine release. Besides, lactate dehydrogenase (LDH) and creatine kinase (CK) downregulation and adiponectin expression play important roles in promoting coronary artery disease. The study aimed to examine the possible cardioprotective effect of members of phosphodiesterase type 5 (PDE-5) inhibitors in epinephrine-induced arrhythmia in rats. Arrhythmia was induced by cumulative boluses of epinephrine (4, 8, 16, 32, 64, and 128 mg/kg) given at 10-min intervals. Rats were randomly allocated into five groups. Group I: Normal control group received only saline. Group II: Rats injected with epinephrine and served as arrhythmia group. Groups III, IV, and V: Rats received daily oral sildenafil (0.5 mg/kg), vardenafil (3 mg/kg), and tadalafil (10 mg/kg), respectively, for 30 days prior to epinephrine injections. Injection of epinephrine to rats decreased heart rate and QTc interval but increased RR interval and duration of arrhythmia. Epinephrine group had lower serum reduced glutathione (GSH) and adiponectin levels and higher serum malondialdehyde (MDA), nitric oxide (NO), heart LDH, and CK contents. Histopathological investigations of epinephrine group provoked necrotic changes with strong positive immunoreactivity for caspases-3. While pretreatment of rats with PDE-5 inhibitors improved GSH and adiponectin contents, ameliorated serum MDA and NO levels and heart LDH and CK contents and corrected epinephrine-induced histopathological changes. PDE-5 inhibitors may delay epinephrine-induced arrhythmia through expression of adiponectin and downregulation of heart LDH and CK.

Cerebrolysin attenuates cerebral and hepatic injury due to lipopolysaccharide in rats.

This study aimed to investigate the effect of cerebrolysin on oxidative stress in the brain and liver during systemic inflammation. Rats were intraperitoneally challenged with a single subseptic dose of lipopolysaccharide (LPS; 300 µg/kg) without or with cerebrolysin at doses of 21.5, 43 or 86 mg/kg. After 4 h, rats were euthanized and the brain and liver tissues were subjected to biochemical and histopathological analyses. Cerebrolysin revealed inhibitory effects on the elevation of lipid peroxidation and nitric oxide induced by LPS. In contrast, the decrease in reduced glutathione level and paraoxonase activity induced by LPS was attenuated by an injection of cerebrolysin in a dose-dependent manner. Moreover, cerebrolysin reduced LPS-induced activation of brain NF-κB and reversed LPS-induced decline of brain butyrylcholinesterase and acetylcholinesterase activities in a dose-dependent manner. Histopathological analyses revealed that neuronal damage and liver necrosis induced by LPS were ameliorated by cerebrolysin dose-dependently. Cerebrolysin treatment dose-dependently attenuated LPS-induced expressions in cyclooxygenase 2, inducible nitric oxide synthase, and caspase-3 in the cortex or striatum as well as the liver. These results suggest that cerebrolysin treatment might have beneficial therapeutic effects in cerebral inflammation. Cerebrolysin might also prove of value in liver disease and this possibility requires further exploration.