Turan Güven

Halothane hepatotoxicity and hepatic free radical metabolism in guinea pigs; the effects of vitamin E

PurposeThe aim of this study was to investigate the relation between halothane hepatotoxicity and hepatic free radical metabolism and to establish a possible protective role of vitamin E against halothane hepatotoxicity.MethodsTwenty-eight guinea pigs were used in the experiments. Halothane (1.5% v/v) in oxygen (100%) was given to the animals for 90 min over three days. Livers from animals were then taken and prepared for the assays. In the enzymatic study, Superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities were measured. As a peroxidation index, the malondialdehyde (MDA) concentration was determined. Also, electron spin resonance (ESR) analysis and electron microscopy (EM) were performed. Results: Superoxide dismutase (1168.3 ± 78.2 U · mg−1) and glutathione peroxidase (14.9 ± 6.2 mIU · mg−1) activities were decreased, but catalase activity (1260.0 ± 250.6 lU · mg−1) and malondialdehyde concentration (11.5 ± 1.8 ppb) were increased in liver tissues exposed to halothane compared with control values (1382.2 ± 91.8 U · mg−1 for SOD, 27.8 ± 5.2 mIU · mg−1 for GSH-Px, 840.2 ± 252.4 IU · mg−1 for CAT and 10.0 ± 1.0 ppb for MDA). Electron spin resonance analysis revealed a peak of CF3 CHCl radical in the exposed tissue. Electron microscopy indicated ultrastructural changes in the hepatic cells of both halothane groups with and without vitamin E treatment.ConclusionHalothane causes impairment in the hepatic antioxidant defense system and accelerates peroxidation reactions. As a result, some ultrastructural changes in hepatic tissues occur due to halothane treatment. Although vitamin E prevents peroxidative damage, it does not ameliorate ultrastructural changes caused by halothane treatment. This shows that halothane toxicity results not only from impaired hepatic antioxidant defense system but also from other, unknown causes.RésuméObjectifCette étude visait à examiner la relation possible entre l’hépatotoxicité à l’halothane et le métabolisme des radicaux libres et à vérifier si la vitamine E protège contre l’hépatotoxicité à, l’halothane.MéthodesVingt-huit cobayes ont été utilisés. De l’halothane (15% v/v) en oxygène (100%) a été administré aux animaux pendant 90 min sur une période de trois jours. Les foies ont alors été prélevés et préparés pour fin d’analyse. Pour l’étude enzymatique, l’activité de la superoxyde dismutase (SOD), de la glutathione peroxydase (GSH-Px) et de la catalase (CAT) a été mesurée. En tant qu ’indice de la peroxydation, la concentration de la malondialdéhyde (MDA) a été déterminée. En outre, on a procédé à des examens à la résonance paramagnétique électronique (Electronic spin resonance: ESR) et à la microscopie électronique (EM).RésultatsL’activité de la superoxyde dismutase (1168,3 ±78,2 U · mg−1) et de la glutathione peroxydase (14,9 ± 6,2 UI · mg−1) a diminué, mais celle de la catalase (1260,0 ± 250,6 Ul · mg−1) ainsi que la concentration de ta malondialdéhyde (11,5 ± 1,8 ppb) ont augmenté dans le tissus hépatique exposé à l’halothane comparativement aux valeurs de contrôle (1382,2 ± 91,8U · mg−1 pour SOD, 27,8 ± 5.2 mUI · mg−1 pour SGH-px, 840 ± 252,4 UI · mg−1 pour CAT et 10,0 ± 1,0 ppb pour MDA). La résonance paramagnétique a révélé un pic de radical CF3CHCl dans les tissus exposés. La microscopie électronique a montré des changements ultrastructuraux dans les cellules hépatiques chez les deux groupes halothane traités ou non à la vitamine E.ConclusionL’halothane provoque une altération du système de défense hépatique antioxydant et accélère les réactions de peroxydation. Il en résulte des changements ultrastructuraux des tissus hépatiques produits par l’exposition à l’halothane. Bien qu’elle prévienne le dommage peroxydatif, la vitamine E n’atténue pas les changements ultrastucturaux produits par l’exposition à l’halothane. Ceci montre que la toxicité à l’halothane résulte non seulement de l’altération du système de défense antioxydant mais aussi d’autres causes non déterminées.

Impaired antioxidant defence in guinea pig heart tissues treated with halothane

PurposeTo investigate the effects of halothane and halothane plus vitamin E treatment on myocardial free radical metabolism in guinea pigs.MethodsFour groups of seven animals were studied; control, halothane, halothane plus vitamin E and vitamin E groups. In the halothane group, halothane 1.5% in oxygen was given for 90 min over three days. In the halothane plus vitamin E group, 300 rng · kg−1 · day−1 vitamin Eim was started three days before the first halothane treatment and continued for three days. Following sacrifice, the hearts were assayed for superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) and malondialdehyde (MDA) level was determined. Electron spin resonance (ESR) analysis and electron microscopy (EM) were also performed.ResultsIn the halothane group, SOD activities and MDA concentrations were increased compared with control and GSH-Px and CAT activities were decreased. In the halothane plus vitamin E group, there were no differences in enzyme activity compared with halothane alone but the MDA level was decreased. In the vitamin E group, enzyme activities were increased compared with control. Mainly the CF3CHCl radical was identified by ESR analysis in heart tissues exposed to halothane and the concentration of this radical was reduced by vitamin E. Electron microscopy showed cytoplasmic vacuolisation and dilation in sarcoplasmic reticulum in the heart tissues exposed to halothane: both were prevented by vitamin E.ConclusionAlthough halothane causes impairment in enzymatic antioxidant defence potential, due to lowered GSH-Px and CAT activity, and accelerates peroxidative reactions in the tissues affected, no subcellular damage occurred. Vitamin E may protect tissues against free radical attack by scavenging toxic free radicals formed in heart tissue during halothane anaesthesia.RésuméObjectifÉtudier les effets de l’halothane et de l’association halothane-vitamine E sur la production myocardique de radicaux libres.MéthodesL’étude portait sur quatre groupes de sept animaux: contrôle, halothane, halothane+vitamine E, et vitamine E. Le groupe halothane a reçu de l’halothane 1,5% en oxygène pendant 90 min pour 3 jours. Le groupe halothane+vitamine E a reçu une doseim de 300 mg · kg−1 · j−1 de vitamine E pendant trois jours avant un premier traitement a l’halothane. Une fois l’animal sacrifié, la superoxyde dismutase (SOD), la glutathion peroxydase (GSH-Px) et catalase (CAT), et la malondialdéhyde (MDA) ont été titrées dans le tissu cardiaque. La résonance paramagnétique électronique (RPÉ) et la microscopie électronique ont complété ces analyses.RésultatsDans le groupe halothane, l’activité de la SOD et la concentration de MDA augmentaient comparativement au contrôle et l’activité de la GSH-Px et de la CAT diminuait. Dans le groupe halothane+vitamine E, l’activité enzymatique ne changeait pas comparativement à l’halothane seul mais le niveau de MDA diminuait. Dans le groupe vitamine E, l’activité enzymatique augmentait comparativement au contrôle. Le radical CF3CHCl était principalement identifié par l’analyse RPÉ dans le tissu cardiaque exposé à l’halothane alors que la vitamine E diminuait la concentration de ce radical. La microscopie électronique révélait une vacuolisation et une dilatation cytoplasmiques du réticulum sarcoplasmique du tissu cardiaque exposé à l’halothane; la vitamine E prévenait ces effets.ConclusionMalgré l’altération par l’halothane de la capacité de protection enzymatique contre l’oxydation, due à la baisse de l’activité de la GSH-Px et de la CAT et l’accélération des réactions peroxydatives dans les tissus affectés, il n’y a pas eu de dommages infracellulaires. La vitamine E protège les tissus contre l’agression des radicaux libres en épurant les radicaux toxiques libérés dans le tissu cardiaque pendant l’anesthésie à l’halothane.

The effect of allopurinol on the liver ultrastructure, reduced glutathione and lipid peroxide levels during liver ischemia in guinea pigs.

1. The preventive effect of allopurinol on reduced glutathione and lipid peroxide levels of the liver and the accompanying ultrastructural changes during liver ischemia was investigated in guinea pigs. 2. Liver glutathione levels decreased significantly while lipid peroxide levels increased slightly in the ischemic group. 3. Allopurinol administered before ischemia resulted in a reverse significant increase in liver glutathione levels and a significant decrease in lipid peroxide levels indicating a protective effect upon cell membrane during ischemia. 4. On the other hand, electron microscopic changes in the liver associated with ischemia could not be altered by allopurinol.

Effects of ultraviolet radiation on the stratum corneum of skin in mole rats

Abstract It is likely that the UV rays will affect the epidermis of mammals. All these negative effects justify the studies on the relation between the UV rays and epidermis. The purpose of this study was to investigate the ultrastructural effects of ultraviolet C radiation (UVC) on the stratum corneum of mole rats epidermis. Mole rats were divided into two as the control and experiment groups. The control group did not receive any radiation while the other groups were irradiated with UV radiation for 52, 112 and 168h. The skin samples were prepared and analyzed by transmission electron microscopy. After the examination, stratum basale, stratum spinosum, stratum granulosum and stratum corneum layers were distinguished. The most drastic effects of UVC were noted in stratum corneum. Lacunae formations and unkeratinized cytoplasmic residues were observed within the horny cells. Depending on dosage and exposal period of the UVC radiation, ultrastructural changes occurred in the stratum corneum on mole rats epidermis.

The effects of ultraviolet C radiation on the ultrastructure of the liver cells of mole rats.

ABSTRACT The aim of this study was to elucidate the ultrastructural changes in the liver cells of mole rats (Spalax leucodon) exposed to ultraviolet radiation (UVR). Thirteen mole rats used in this study were caught from nature. They were divided into four groups. The first group was separated as a control and was not given any radiation. The rest were exposed to ultraviolet C (UVC) radiation for 7, 14, and 21 days. The electron microscopic examinations revealed that significant ultrastructural changes occurred in the liver tissue. These changes were the reduction in cytoplasmic organelles, dilatation in rough endoplasmic reticulum, impairment of nucleus membrane, and broadened and vacuolated mitochondria in the cytoplasm. Also, UVC radiation caused significant changes in liver enzymes of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and gama-glutamiltransferase values. After long-term exposure to radiation, some excessive ultrastructural changes occurred. These results indicated that longer exposure to UVR would cause more ultrastructural effects on the liver cells and liver enzymes.