Biomedical subjects

M Ahotupa

Publications and source records attributed to M Ahotupa.

At least 55 records · Page 3Linked to original sources

PubMed1995

Chronic UVB irradiation induces superoxide dismutase activity in human epidermis in vivo.

In order to study the effects of repeated UVB exposures on the epidermal antioxidant defence system, we obtained epidermis samples from male volunteers who were exposed to chronic UVB irradiation. Chronic UVB irradiation was shown to be accompanied by induction of epidermal superoxide dismutase (SOD) activity in vivo, while the activities of the other antioxidant enzymes were not significantly changed. The repeated exposure of the epidermis to UVB irradiation was not accompanied by accumulation of products of lipid peroxidation reactions. As superoxide dismutase is of major importance in scavenging the reactive oxygen species, the UVB-induced changes in SOD activity might provide the epidermis a way of defending itself against the effects of chronic UVB irradiation.

Adolescent↗

PubMed1995

Abdominal position of the rat testis is associated with high level of lipid peroxidation.

Experimental cryptorchidism in the adult rat induces lipid peroxidation as a sign of oxidative stress. To further elucidate the role of free radicals and antioxidant enzymes in the degeneration of testis in cryptorchidism, we first studied testes of untreated rats before and after the normal testicular descent. In the second experiment, primary unilateral cryptorchidism was induced by surgically attaching one testis of each rat to the abdomen before testicular descent. The level of lipid peroxidation was detected by formation of fluorescent chromolipids and diene conjugates. At the age of testicular descent (18-21 days), the level of fluorescent chromolipids dropped to one third (p < 0.05). Correspondingly, the level of diene conjugates was 69% (p < 0.05) higher at 18 than at 30 days of age. The antioxidant enzyme activities did not change at the time of testicular descent. Primary unilateral cryptorchidism was induced at the age of 13 days. At 25 or 35 days of age, the level of diene conjugates was higher in the cryptorchid testes than in the contralateral scrotal testes (+39%, p < 0.01, and +51%, p < 0.001, respectively). In the abdominal testes, the mRNA of CuZn superoxide dismutase (SOD) was increased by 69% (p < 0.05) at 25 days, whereas by 35 days of age enzymatic CuZn SOD activity was slightly decreased and catalase activity increased. The present results show that the abdominal position of the testis, either before normal testicular descent or in experimental cryptorchidism, is associated with a high level of lipid peroxidation. The data provide evidence that increased production of reactive oxygen species could contribute to degeneration of the cryptorchid testis. The oxidative testis. The oxidative stress in the cryptorchid testis is not explained by inactivation of antioxidant enzymes.

Aging↗

PubMed1994

Antioxidant enzyme activities and oxidative stress in human breast cancer.

We have analysed products of lipid peroxidation reactions and activities of antioxidant enzymes in cancerous breast tissue and in corresponding reference tissue. In addition, the serum lipid peroxidation and peroxyl-radical-trapping capacity of breast cancer patients were compared to those of healthy subjects. A total of 23 patients with breast cancer participated in this study. In the cancerous tissue, catalase activity was lower than in the reference tissue, while the activities of superoxide dismutase, glutathione peroxidase and the hexose monophosphate shunt were elevated. The content of thiobarbituric-acid-reactive material was slightly lower in the cancerous tissues, but the levels in serum were found to be elevated in patients with breast cancer. The amounts of conjugated diene double bonds were essentially equal both in the cancerous and in the reference tissue. Moreover, in breast cancer patients the serum levels of diene conjugation and the peroxyl-radical-scavenging capacity did not differ from those measured in healthy subjects. This study indicates that the antioxidant defence system is altered in cancerous breast tissues, but does not support the hypothesis suggesting that formation of lipid peroxides in the tumour tissue itself is of primary importance in the carcinogenesis.

Antioxidants↗

PubMed1994

Alterations of drug metabolizing and antioxidant enzyme activities during tamoxifen-induced hepatocarcinogenesis in the rat.

The triphenylethylene drug tamoxifen is a hepatocarcinogen in rats, has genotoxic potential and may produce carcinoma of the endometrium in humans, while the structurally closely related toremifene has no carcinogenic or genotoxic potential. We have investigated the effects of long-term treatment with tamoxifen and toremifene on the activities of drug metabolizing and antioxidant enzymes in rat liver. Female Sprague-Dawley rats were dosed with equimolar doses of tamoxifen (11.3 and 45 mg/kg) and toremifene (12 and 48 mg/kg) for 12 months and were killed after 2 days, 5 weeks, 3, 6 and 12 months of treatment. After 12 months most rats treated with the high dose of tamoxifen had hyperplastic nodules and hepatocellular carcinomas, while in rats given toremifene or the low dose of tamoxifen, only foci were observed. A striking observation was strong inhibition of the hexose monophosphate shunt (HMS) by tamoxifen and toremifene, which, except in the group given the high dose of tamoxifen, lasted throughout the treatment period. Both antiestrogens induced susceptibility to oxidative stress, as indicated by decreased hepatic contents of reduced glutathione and by increased peroxidation potential of microsomal preparations. The activity of glutathione S-transferase was permanently induced by the high dose of tamoxifen from 5 weeks onwards and was greater in tamoxifen-induced liver tumors than in corresponding macroscopically normal tissue. Similarly, the activity of HMS was elevated by the high dose of tamoxifen at the latest time points, and a further elevation was seen in tamoxifen-induced liver tumors. No such alteration in glutathione S-transferase or HMS activity was seen in animals treated with toremifene or with the low dose of tamoxifen. In conclusion, tamoxifen and toremifene differ markedly with respect to production of liver tumors, and this difference in hepatocarcinogenic potential is reflected in differential effects on glutathione-S-transferase and HMS activities in rat liver.

Animals↗

PubMed1994

Protective effect of antioxidants against free radical-mediated lipid peroxidation induced by DON or T-2 toxin.

An experiment was conducted on rats to investigate the capacity of antioxidants to protect against acute toxicity caused by DON or T-2 toxin. Male rats were fed two different feeds. One group received a feed deficient in vitamins C and E and selenium, whereas the other group was fed with a feed enriched in antioxidants. After two weeks, selected groups of rats were administered orally a single dose of DON or T-2 toxin. After the treatment with mycotoxins, all rats were decapitated. The livers were analyzed for TBARS values, hepatic GSH content and for the activities of CyP-450, CAT, SOD and GSH-TR. Increases in lipid peroxides of 21% and 268% were observed in those rats which did not receive the supplement of antioxidants and which were administered DON or T-2 toxin, respectively. There was no significant increases in the TBARS values in the groups receiving DON with selenium and vitamins, but increases of 57% and 79% were recorded in the groups administered T-2 toxin and antioxidants. Furthermore, in the groups fed the deficient feed and administered DON or T-2 toxin, the lipid peroxidation increased by 33% and 307%, respectively. No mortality, and a lower number of intoxicated animals were observed in rats fed a diet supplemented with antioxidants. Significant decreases of GSH, CAT, SOD, CyP-450 and GSH-TR were recorded in treated rats receiving the deficient feed. The results of this study demonstrate that trichothecenes stimulate lipid peroxidation with consequent decrease of GSH content, but that the dietary use of selenium, alpha-tocopherol and ascorbic acid provides protection against acute toxicosis caused by DON or T-2 toxin.

Animals↗

PubMed1994

Free radical reaction products and antioxidant capacity in arterial plasma during coronary artery bypass grafting.

Oxygen free radicals mediate the ischemia-reperfusion damage in animal hearts, but their role in human beings is still controversial because of the low xanthine oxidase level in the human heart. Besides ischemia-reperfusion, cardiac operation also includes other major interventions that might generate free radicals but have not been systematically studied. We studied the cases of nine patients throughout coronary artery operations, including general anesthesia, heparin, protamine and administration of cardioplegic solution, extracorporeal circulation, and heart reperfusion. Arterial plasma was assayed for malondialdehyde, diene conjugates, and fluorescent chromolipids, and plasma antioxidant activity was estimated from the ability to trap peroxyl radicals. Anesthesia, surgical procedures, or heparin administration did not change these parameters. Extracorporeal circulation decreased the plasma concentration of diene conjugates immediately, whereas other compounds remained unaltered. When these concentrations were corrected for hemodilution, the amount of fluorescent chromolipids actually increased after 5 minutes of extracorporeal circulation to 177% +/- 14% (mean +/- standard error of the mean), diene conjugates increased to 138% +/- 12%, and plasma antioxidant capacity increased to 144% +/- 12% of the awake value. Fluorescent chromolipid values remained at 156% to 177% throughout the perfusion and decreased to 130% +/- 13% 1 hour after perfusion. Diene conjugate levels and antioxidant capacity were 123% to 144% and 143% to 161%, respectively, from baseline during perfusion and 119% +/- 5% and 135% +/- 9%, respectively, 1 hour after perfusion. Heart reperfusion or protamine administration showed no additional increases. Malondialdehyde concentrations varied and showed no statistically significant alterations. We conclude that extracorporeal circulation devices induce generation of free radicals and plasma antioxidant activity, which are different from the damage caused by ischemia-reperfusion.

Aged↗

PubMed1993

Lucigenin and linoleate enhanced chemiluminescent assay for superoxide dismutase activity.

The xanthine/xanthine oxidase dependent chemiluminescence was enhanced both by lucigenin and linoleate to create a sensitive, specific, and rapid chemiluminescent method for superoxide dismutase (SOD) activity determination. A pH optimum at around 10.0 was found both for the chemiluminescence and its inhibition by SOD. At this pH, a linear inhibition response to concentrations from 0.01 to 100 ng/ml of bovine Cu,Zn SOD could be established, with a 50% inhibitory concentration of 0.75 ng/ml. As little as 0.17 fmol of Cu,Zn SOD per test can be detected. With a slightly lower sensitivity, the method is operative at pH 7.4, too. Both Cu,Zn SOD and Mn SOD can be assayed. The rationale of the assay is in combining a superoxide-producing enzymatic system with linoleate amplification to enhance the sensitivity of the chemiluminescence to inhibition by SOD activity. Applicability of the method to biological samples was tested with a standard addition experiment.

Acridines↗

PubMed1993

Activities of antioxidant enzymes and lipid peroxidation in endometrial cancer.

Antioxidant enzyme activities and lipid peroxidation were analysed in normal endometrium and endometrial cancer tissues from Finnish and Japanese patients. The catalase and glutathione peroxidase activities of normal endometrium were significantly lower in Finns than in Japanese. Lipid peroxidation was slightly higher in endometrial cancer as compared with normal endometrium both in the Finns and in the Japanese. When cancer tissues were compared with normal endometrium both in Finns and Japanese the activity of superoxide dismutase was significantly lower in cancer tissue than in normal endometrium. In Finns glutathione S-transferase activity was also lower in endometrial cancer tissue than in normal endometrium, and a similar tendency was also found in Japanese. This study suggests that endometrial cancer tissue is associated with an impaired enzymic antioxidant defence system.

Catalase↗

PubMed1993

Dietary fat- and phenobarbital-induced alterations in hepatic antioxidant functions of mice.

Inbred strains of mice with differential response to known tumor promoters were compared with respect to their susceptibility to modulation of hepatic antioxidant enzymes by long-term treatment with high fat diet (HF) and phenobarbital (PB). Mice of the C57BL/6J (C57), C3H/HeOuJ (C3H) and DBA/2J (DBA) strains were fed diets containing low (5%) or high (15%) amounts of fat (sunflower oil) for 26 weeks from the age of 6 weeks onwards. Groups of mice on the 5% fat diet received 0.05% PB in their drinking water from 12 to 22 weeks of age. Mice of the C57 strain are known to be refractory to promotion of hepatocarcinogenesis, the C3H strain has a high incidence of spontaneous tumors and is sensitive to promotion by HF and PB, and the DBA strain is especially sensitive to promotion by PB. Within all strains of mice, and in both dietary groups, the degree of oxidative stress in the liver was found to increase with age, as was indicated by the increased amounts of TBA reactive material (lipid peroxidation) and decreased glutathione (GSH) and phospholipid contents of the tissue. HF elevated the amount of TBA reactive material in the liver of C57 and C3H mice, induced GSH-peroxidase and Mn-superoxide dismutase activities in the C3H strain, and depressed the hexose monophosphate shunt activity within all mouse strains. PB drastically decreased the amount of TBA reactive material in the liver in all mouse strains, increased catalase activity in all strains and the activity of GSH-peroxidase in the C3H and DBA strains. The above strain differences in responses of hepatic antioxidant functions to HF and PB parallel the differential responsiveness of these mouse strains to promotion of hepatocarcinogenesis by these agents, and the increased antioxidant capacity was proportional to susceptibility to tumor promotion.

Animals↗

PubMed1993

Pregnancy-induced hypertension is associated with changes in maternal and umbilical blood antioxidants.

Seventeen pregnancies with pregnancy-induced hypertension (PIH) and 28 control pregnancies were analyzed with regard to maternal and fetal blood antioxidants and lipid peroxidation products (conjugated dienes). In PIH, maternal blood levels of conjugated dienes were higher than in normal pregnancy. Also the activities of platelet and plasma glutathione peroxidase (GSHPx) were higher in PIH. In umbilical cord blood, the appearance of conjugated dienes, the concentration of vitamin E and the activity of erythrocyte GSHPx were lower than the corresponding maternal values. There was no difference between PIH and normal pregnancy in the appearance of conjugated dienes in cord blood, but erythrocyte GSHPx and plasma vitamin A were lower in PIH. Cord blood plasma vitamin A showed a negative correlation to maternal mean arterial pressure. We suggest that lipid peroxidation is involved in the pathogenesis of maternal PIH, and it may also have effects on the vascular function and antioxidant status of the fetus.

Adult↗

PubMed1992

Impaired detoxification of reactive oxygen and consequent oxidative stress in experimentally cryptorchid rat testis.

The effect of experimental cryptorchidism on the level of oxidative stress and antioxidant functions in rat testis was studied. Adult male Sprague-Dawley rats were rendered unilaterally cryptorchid (by suturing one testis to the abdominal wall) and killed 1, 3, or 7 days after the operation. As an indicator of oxidative stress, lipid peroxidation was measured by the diene conjugation method in testis homogenates. The activities of the antioxidant enzymes were determined either in the 10,000 x g supernatant fraction (glutathione [GSH] peroxidase, GSH transferase, hexose monophosphate shunt) or in crude testis homogenates (superoxide dismutase, catalase). An expected reduction (48%) in weight of the abdominal testes was evident by postoperative Day 7. The catalytic activities per testis of superoxide dismutase (Cu/Zn form) and catalase were found to decrease in cryptorchidism. The effect was seen on the first postoperative day and was most profound on Day 7 after surgery. The principal antioxidant enzyme, superoxide dismutase, was most sensitive to cryptorchidism, the activity in the abdominal testes being 74% or 85% (per gram of tissue or per whole testis, respectively; p less than 0.01). After impairment of the reactive oxygen detoxifying capacity, lipid peroxidation was increased in the abdominal testis by 46% (p less than 0.01) on postoperative Day 7. Slight concomitant increases were detected in the activities of GSH-peroxidase (p less than 0.01), GSH-transferase (p less than 0.001), and the hexose monophosphate shunt (p less than 0.001). This effect was seen only when calculated per gram of tissue, not per whole testis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Pro-oxidant effects of normobaric hyperoxia in rat tissues.

Rats were exposed to 100% O2 atmosphere for 12, 36 or 48 h, and their lungs, brain, liver and kidneys were studied for signs of oxidative damage. Oxidative damage at molecular level was estimated by: (1) the appearance of conjugated diene double bonds and (2) the amount of fluorescent chromolipids in lipids extracted from tissues. As important intracellular regulators of oxidative stress, the response of enzymes detoxifying reactive oxygen species was also studied. Macroscopically, the brain and the lungs were most susceptible to oxygen-induced effects. As an indication of oxidative tissue damage, hyperoxia caused accumulation of fluorescent chromolipids in brain and lung tissues, whereas diene conjugation did not reveal any signs of lipid peroxidation. Accumulation of fluorescent chromolipids was most prominent in the brain, where 99 and 138% increases over the control were detected after 36 and 48 h hyperoxia, respectively. Fluorescent chromolipids appeared in urine already before their concentrations were elevated in tissues. The activity of superoxide dismutase in the brain was initially decreased, followed then by a slight induction of activity at the later time-points. Pulmonary and hepatic catalase activities were markedly decreased after prolonged (36 and 48 h) hyperoxia. In conclusion, fluorescent chromolipid formation seems to be a sensitive indicator of hyperoxia-induced oxidative damage in rat tissues. The lipid peroxidation-derived fluorescent chromolipids are eliminated from the body via urinary excretion. Moreover, impaired detoxication of reactive oxygen may be implicated in tissue damage due to hyperoxia.

Animals↗

PubMed1991

Lipid peroxidation products, selenium-dependent glutathione peroxidase and vitamin E in normal pregnancy.

Twenty healthy women with normal pregnancy were simultaneously analysed with regard to lipid peroxidation products, selenium-dependent glutathione peroxidase and vitamin E. Conjugated diene double bonds, fluorescent chromolipids and thiobarbituric acid-reactive material were analysed as breakdown products of lipid peroxidation. The level of conjugated dienes in serum rose more than 45% when pregnancy advanced from the first to second trimester, but after that it declined almost to the same level as in the first trimester. The fluorescent chromolipids tended to behave in the same way. While the lipid peroxidation products reached their highest level in the second trimester, the activity of glutathione peroxidase rose progressively till the third trimester both in erythrocytes and platelets, in spite of the stable concentration of selenium in blood and plasma. The concentration of vitamin E in serum rose progressively till the end of pregnancy, but in the relation of vitamin E to cholesterol only a slight rising tendency was noted. We suggest that in normal pregnancy lipid peroxidation is controlled by adequate antioxidative response.

Adult↗

PubMed1991

Mechanisms of fat-related modulation of N-nitrosodiethylamine-induced tumors in rats: organ distribution, blood lipids, enzymes and pro-oxidant state.

Groups of rats, either dosed with N-nitrosodiethylamine (NDEA) for 10 weeks (from the age of 7 to 17 weeks) or untreated, were fed diets containing either 2% (low fat, LF) or 30% polyunsaturated fat (high fat, HF) on an equicaloric basis from 5 weeks until rats were 43 weeks old. Biochemical parameters were measured during and at the end of the experiment in various organs, blood, urine and exhaled air, for correlation with the presence or absence of tumors. The HF diet tended to increase the number of hepatic tumors induced by NDEA, while the number of extrahepatic tumors was higher in rats fed on the LF diet; also the overall tumor incidence was higher in the LF group. In the HF/NDEA group, only two benign extrahepatic tumors were found. Plasma total and free cholesterol and triglyceride concentrations were lower in the HF than the LF group without NDEA treatment. In animals bearing liver and/or extrahepatic tumors all plasma lipid concentrations were lower than in tumor-free animals. Only minor or no changes were detected in blood catalase activity, malondialdehyde level, reduced glutathione (GSH) level or GSH-related enzymes and excretion of thioethers in the urine due to dietary modulation or NDEA. Changes in the liver that were associated with the HF diet were: (i) increased amounts of some polyunsaturated fatty acids and of total phospholipids in liver microsomes; (ii) an enhanced level of lipid peroxidation in liver; (iii) a decrease in liver glutathione levels during NDEA treatment, with a simultaneous adaptive increase in superoxide dismutase levels, and a decrease in renal glutathione levels in both treated and untreated groups; (iv) enhanced microsomal induction of aminopyrine N-demethylase and epoxide hydrolase activities by NDEA, and (v) decreased hexose monophosphate shunt (HMS) activity. All mono-oxygenase activities were lower, and the activities of epoxide hydrolase, UDP-glucuronosyltransferase and HMS were higher, in liver tumors than in non-tumorous liver of similarly-treated rats. Neither diet nor NDEA had a major effect on drug-metabolizing enzyme activities in lung and kidney. HF diet significantly increased ethane exhalation (an indicator of the whole-body pro-oxidant state) over those on the LF diet: in rats on either diet, it was further increased when NDEA was given. Ethane exhalation was still elevated 30 weeks after the cessation of NDEA treatment. Our results suggest an association between the observed changes in biochemical parameters, notably oxidative stress, due to dietary modulation and the altered tumor incidence and organ distribution of tumors induced by NDEA.

Alanine Transaminase↗

PubMed1991

Effects of in vitro UVA irradiation and PUVA treatment on membrane fatty acids and activities of antioxidant enzymes in human keratinocytes.

Human Keratinocytes (NCTC 2544) in culture were exposed to either plain ultraviolet A (UVA) irradiation or to 8-methoxypsoralen plus UVA (PUVA) treatment. Lipid peroxidation, activities of antioxidant enzymes, and percentage amounts of 14C-arachidonic acid in various cellular lipid subclasses and in the culture medium were measured. Both UVA irradiation and PUVA treatment induced significant changes in the distribution of arachidonic acid and increased the liberation of arachidonic acid from membrane phospholipids. At 24 h after either UVA irradiation or PUVA treatment the formation of thiobarbituric acid reactive material was significantly increased, whereas the amount of conjugated dienes was unaffected. The activities of the antioxidant enzymes, catalase and superoxide dismutase, were already significantly decreased at 0.5 h after UVA irradiation or PUVA treatment. The enzyme activities were partially restored during the following 24 h incubation. From the present study, we suggest that in keratinocytes both plain UVA irradiation and PUVA treatment induce changes in the distribution of membrane fatty acids and cause an impairment in the enzymic defense system against oxidative stress.

Arachidonic Acids↗

PubMed1991

In-vivo effects of solar-simulated ultraviolet irradiation on antioxidant enzymes and lipid peroxidation in human epidermis.

The effects of solar-simulated UV-irradiation on the activity of antioxidant enzymes and the amount of diene conjugation were studied in human epidermis in vivo. A single dose of UV-irradiation was found to result in a transient reduction in superoxide dismutase activity and this was followed by increased amounts of conjugated diene double bonds, an index for oxidative stress. This suggests that in-vivo exposure of human epidermis to solar-simulated UV-irradiation causes changes in the enzymic antioxidant defence system which, in turn, are accompanied by increased level of oxidative stress.

Adolescent↗

PubMed1991

UVB irradiation induces lipid peroxidation and reduces antioxidant enzyme activities in human keratinocytes in vitro.

Exposure of human keratinocytes to UVB irradiation resulted in formation of conjugated double bonds and thiobarbituric acid reactive material. The activities of superoxide dismutase and catalase, enzymes which protect cells against oxidative damage, were concomitantly reduced. The present study suggests that in keratinocytes, exposure to UVB irradiation leads to a chain of events resulting in lipid peroxidation reactions accompanied by an impairment of the cellular defence system against reactive oxygen species. These phenomena may act synergistically in UVB-induced cutaneous pathological processes, such as carcinogenesis.

Catalase↗

PubMed1991

Effects of ultraviolet A and B irradiation on lipid peroxidation and activity of the antioxidant enzymes in keratinocytes in culture.

Human keratinocytes (NCTC 2544) in culture were exposed to various combinations of ultraviolet A (UVA) and UVB irradiation and at 0.5 h postirradiation the level of lipid peroxidation and activities of antioxidant enzymes were measured. The results suggest that UV irradiation is capable of inducing lipid peroxidation reactions, as parameters of which the amount of thiobarbituric acid-reactive material and the number of conjugated diene double bonds were measured. Both UVA and UVB irradiation were also found to affect the activities of antioxidant enzymes. Following UVB irradiation the activity of superoxide dismutase (Cu/Zn form) was decreased, and combination of increasing doses of UVA irradiation to a given dose of UVB irradiation decreased the activity of both catalase and superoxide dismutase. In summary, this study suggests that both UVA and UVB irradiation are capable of inducing lipid peroxidation reactions and an impairment of the enzymic antioxidant system in human keratinocytes in culture.

Antioxidants↗