Similar protective effect of ischaemic and ozone oxidative preconditionings in liver ischaemia/reperfusion injury

• Published in: Pharmacological research 2002-04, Vol.45 (4), p.333-339
• Main Authors: Ajamieh, Hussam, Merino, Nelson, Candelario-Jalil, Eduardo, Menéndez, Silvia, Martinez-Sanchez, Gregorio, Re, Lamberto, Giuliani, Attilia, Sonia Leon, Olga
• Format: Article
• Language: English
• Subjects: Animals; Calcium - metabolism; Calpain - metabolism; Ischemic Preconditioning; Lipid Peroxidation - drug effects; Liver - metabolism; Liver - pathology; Liver Circulation - physiology; Liver Function Tests; Male; Oxidants, Photochemical - pharmacology; Ozone - pharmacology; ozone, liver ischaemia/reperfusion, oxidative stress; Proteins - metabolism; Rats; Rats, Wistar; Reperfusion Injury - pathology; Reperfusion Injury - prevention & control; Sulfhydryl Compounds - metabolism; Xanthine Dehydrogenase - metabolism; Xanthine Oxidase - metabolism
• ISSN: 1043-6618; 1096-1186
• DOI: 10.1006/phrs.2002.0952

Many studies indicate that oxygen free-radical formation after reoxygenation of liver may initiate the cascade of hepatocellular injury. It has been demonstrated that controlled ozone administration may promote an oxidative preconditioning or adaptation to oxidative stress, preventing the damage induced by reactive oxygen species (ROS) and protecting against liver ischaemia-reperfusion (I/R) injury. On the basis of those results we postulated that ozone treatment in our experimental conditions has biochemical parameters similar to the ischaemic preconditioning (IscheP) mechanism. Four groups of rats were classified as follows: (1) sham-operated animals subjected to anaesthesia and laparotomy, plus surgical manipulation; (2) I/R animals were subjected to 90 min of right-lobe hepatic ischaemia, followed by 90 min of reperfusion; (3) IscheP, previous to the I/R period (as in group 2): animals were subjected to 10 min of ischaemia and 10 min of reperfusion; (4) ozone oxidative preconditioning (OzoneOP), previous to the I/R period (as in group 2): animals were treated with ozone by rectal insufflation 1 mg kg−1 . The rats received 15 ozone treatments, one per day, of 5–5.5 ml at the ozone concentration of 50μ g ml −1. The following parameters were measured: serum transaminases (AST, ALT) and 5′ -nucleotidase (5 ′-NT), with morphological determinations, as indicators or hepatocellular injury; total sulfhydryl groups, calcium levels and calpain activity as mediators which take part in xanthine deshydrogenase (XDH) conversion to xanthine oxidase (XO) (reversible and irreversible forms, respectively); XO activities and malondialdehyde + 4-hydroyalkenals as indicators of increased oxidative stress. AST, ALT levels were attenuated in the IscheP ( 130 ± 11.4 and 75 ± 5.7 U l −1) with regard to the I/R group ( 200 ± 22 and 117 ± 21.7 U l −1) while the OzoneOP maintained both of the enzyme activities ( 89.5 ± 12.6 and 43.7 ± 10 U l −1) without statistical differences ( P< 0.05) in comparison with the sham-operated ( 63.95 ± 11 and 19.48 ± 3.2 U l−1 ). Protective effects of both the preconditioning settings on the preservation of total sylfhydryl groups (IscheP: 6.28 ± 0.07, OzoneOP: 6.34 ± 0.07 μ mol mg prot −1), calcium concentrations (IscheP: 0.18 ± 0.09, OzoneOP: 0.20 ± 0.06 μ mol mg prot −1), and calpain activity (IscheP: 1.04 ± 0.58, OzoneOP: 1.41 ± 0.79 U mg prot −1) were observed. Both of the preconditionings attenuated the increase of total XO associated to I/R