Verapamil attenuates postischemic oxidative injury in the rat liver.
We assessed the effects of the calcium channel blocker verapamil on postischemic oxidative injury in the rat liver. In the untreated rats, the values of tissue lipid peroxidation products (thiobarbituric acid-reactive substances) remained unchanged during 90 min of warm ischemia. However, the values increased significantly after the next 60 min of reperfusion compared with those in the sham-operated rats (P less than 0.01). Intravenous infusion of verapamil (5 micrograms.kg-1.min-1) significantly reduced the extent of lipid peroxidation during reperfusion compared with that in the untreated rats (P less than 0.02). The percentages of tissue water content and the serum lactate dehydrogenase activities after 60 min of reperfusion were significantly lower in the treated rats than in the untreated rats (P less than 0.02 and P less than 0.01, respectively). We also investigated the influence of verapamil on superoxide-generating activity determined by the superoxide-dependent cytochrome c reduction of peritoneal polymorphonuclear leukocytes (PMNs) harvested from normal, non-ischemic, and non-treated rats in vitro. This demonstrated that there was no apparent effect with the highest verapamil concentration level (8 microM) observed in the rat plasma during our experiment. These findings suggest that verapamil might reduce the postischemic oxidative injury in the rat liver by mechanisms perhaps not related to the suppression of rat PMNs superoxide-generating activity.
Ishii
K
K
Department of Pediatric Surgery, Faculty of Medicine, Kyushu University Hospital, Fukuoka, Japan.
Arima
T
T
Suita
S
S
D000818:Animals; D001834:Body Water / Q000378:metabolism; D007262:Infusions, Intravenous; D007770:L-Lactate Dehydrogenase / Q000097:blood; D015227:Lipid Peroxidation / Q000187:drug effects; D008107:Liver Diseases / Q000378:metabolism*; D008297:Male; D009504:Neutrophils / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D015427:Reperfusion Injury / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism; D013858:Thiobarbiturates; D014700:Verapamil / Q000494:pharmacology*
D013858:Thiobarbiturates; D013481:Superoxides; D014700:Verapamil; D007770:L-Lactate Dehydrogenase; C029684:thiobarbituric acid