Peroxisomal enzymes and 8-hydroxydeoxyguanosine in rat liver treated with perfluorooctanoic acid

Although peroxisome proliferators are considered non-genotoxic agents, most of them, nevertheless, were found to promote and/or induce, hepatocellular carcinoma (HCC) in rodents. The aim of the present study is, first, to investigate whether the peroxisome proliferator perfluorooctanoic acid (PFOA) possesses inherent liver cancer promoting activity, and second, to study the possible mechanisms involved. To acheive these aims two protocols have been applied, a biphasic protocol (initiation by diethyl-nitrozamine (DEN) 200 mg/kg i.p. followed by treatment with 0.005% or 0.02% perflourooctanoic acid (PFOA) for 14 and 25 weeks) and a triphasic initiation, selection-promotion (IS) protocol (initiation by giving 200 mg/kg DEN i.p. followed by a selection procedure for 2 weeks consisting of giving 0.03% 2-acetylaminofluorene (2-AAF) in diet). In the middle of this treatment a single oral dose of carbon tetrachloride (2.0 ml/kg) was given, followed by giving diet containg 0.015% of PFOA for 25 weeks. After applying both protocols, our results showed slight increase in the catalase activity while acyl CoA oxidase activity was markedly increased. Both experiments indicated that PFOA has a liver cancer promoting activity. Other groups of rats were given either basal diet or diet containing 0.02% PFOA. Five or nine weeks later they were sacrificed and the levels of 8-hydroxydeoxyguanosine in the isolated DNA were estimated. The data showed a slight nonetheless insignificant increase in 8-hydroxydeoxyguanosine. From the present data, it is concluded that PFOA is a true liver cancer promoter that may not require extensive initial DNA damage for its promoting activity.     

Administration of ciprofibrate to lactating mothers induces PPARα-signaling pathway in the liver and kidney of suckling rats

It is well known that the hypolipidemic drug ciprofibrate induces peroxisome proliferation in rodent liver, which in turn leads to the oxidative stress, and modifies some parameters related to cell proliferation and apoptosis. The administration of ciprofibrate to rats during the lactating period determined in their pups significant modifications in hepatic peroxisome enzyme activities, induction of the PPARalpha-target gene, Cyp4a10, and perturbation in cell proliferation and apoptosis, which affected the size of the liver. Moreover, this modification was associated to about two-fold induction of mRNA-PPARalpha. On the contrary, in the kidney, although a similar two-fold up-regulation of PPARalpha was detected, the induction of both peroxisomal enzyme activities and Cyp4a10 were weak, and no alterations were detected, neither in cell cycle nor in the size of the tissue. Our results indicate that the response to ciprofibrate is stronger in the liver than in the kidney of newborn rats.     

Rat liver mitochondrial enzyme activities in hypoxia.

Rat liver mitochondrial enzyme activities were measured after exposing the animals to the atmospheric pressure of 380 mm Hg for 5 h and 14 days. Succinate dehydrogenase and succinate oxidase activities increased significantly during the hypoxic period of 14 days. No change was observed in cytochrome oxidase activity. Malate dehydrogenase and glutamate dehydrogenase activities increased somewhat, but not significantly. The efficiency of oxidative phosphorylation (the ADP:O ratio) in the isolated mitochondria remained unchanged. The exact mitochondrial protein values showed a 15% decrease as compared with the control group. The concentrations of cytochromes did not change significantly in the hypoxic group. During the short hypoxic period succinate dehydrogenase, succinate oxidase and cytochrome oxidase activities increased as compared with those in the control group.     

Multiple plasma enzyme activities in liver disease

The measurement of the plasma activities of glutamic-oxaloacetic and glutamic-pyruvic transaminases, aldolase, cholinesterase, and isocitric, lactic, and phosphogluconic dehydrogenases in random samples of blood was found to be of no value in the differential diagnosis of hepatitis, obstructive jaundice, hepatic cirrhosis, and neoplastic conditions involving the liver. Serial determinations of the enzyme activities provided useful information about the course of certain hepatic disorders, particularly acute viral hepatitis.     

Morphometry of the kidney in rat pups from uninephrectomized mothers

Background: The present study was designed to explore whether maternal renal dysfunction affects fetal kidney development and if the effects are lasting during the postnatal development. Methods: Kidneys of 1-day-old and 6-week-old pups from mothers which were uninephrectomized on day 5 of gestation were studied. Results: One day after birth, both the number of immature glomeruli and average volume of mature glomeruli of the neonates from uninephrectomized mothers were significantly larger than those from sham-operated mothers. Six weeks after birth, no significant differences in parameters of the kidney were observed between the pups from uninephrectomized and those from sham-operated mothers. Furthermore, blood urea nitrogen (BUN) concentration in adult female rats was determined at various days after uninephrectomy. BUN concentration in uninephrectomized rats was significantly higher than that in sham-operated ones. Conclusions: These results suggest that the fetal kidney development is accelerated by the elevated BUN level following maternal uninephrectomy and that the renotropic activity does not last during the postnatal developmental period. © 1994 Wiley-Liss, Inc.     

Voluntary and involuntary maternal separation in guinea pig pups with mothers required to forage

Lactating guinea pigs required to leave a nest box to obtain food were observed to be separated from their pups almost 10% of the time on Days 13-15 postpartum. The duration of separation was greater in the dark than in the light, and was not different for mothers/litters exposed to low (LFD) versus high (HFD) foraging demand. Subsequently, LFD and HFD pups as well as pups reared under standard laboratory conditions (SLC) all exhibited vocalization and plasma cortisol responses to involuntary maternal separation. However, several effects of rearing were also observed. HFD pups vocalized less during separation and had higher resting cortisol levels than did SLC pups; LFD and HFD males spent less time in contact with the mother in a test cage than did SLC males. These effects are discussed in terms of the importance of the physical environment in shaping infant-mother interactions and the infant's perception of control.     

Delayed effects of the terms of separation of rat pups from lactating females and low-protein diet on enzyme activity in digestive and non-digestive organs

Early and late separation of rat pups from lactating females and combined effects of the terms of separation and low-protein diet are essential for the formation of enzymes (maltase, alkaline phosphatase, aminopeptidase M, and glycyl-L-leucine dipeptidase) in the large and small intestine, liver and kidneys of adult animals. Similarities and differences in the enzyme reactions to early and late weaning and to a combination of untimely weaning and low-protein diet were detected. __________ Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 145, No. 6, pp. 621–625, June, 2008     

Effects of melatonin on lipid peroxidation and antioxidative enzyme activities in the liver,kidneys and brain of rats administered with benzo(a)pyrene

Benzo(a)pyrene [B(a)P] is a widespread pollutant with a mutagenic, carcinogenic and strong prooxidative properties. The present study evaluated the melatonin effects on lipid peroxidation products levels and on activity of antioxidative enzymes in the course of B(a)P intoxication. Control rats were treated with 0.9% NaCl; another group was given 10 mg melatonin/kg bw; a third group was injected twice a week with B(a)P at the dose of 10 mg/kg bw; the fourth group received both B(a)P and melatonin at the dose as mentioned above. The experiment continued for 3 months. In homogenates of brain, liver and kidneys lipid peroxidation was appraised by evaluation of malonyldialdehyde and 4-hydroxyalkenal (MDA+4HDA) levels. Activities of glutathione peroxidase (GPx), superoxide dysmutase (SOD) and catalase (CAT) and concentration of reduced glutathione (GSH) were also estimated. In animals receiving both B(a)P and melatonin, lower levels of MDA+4HDA were observed in all organs as compared to the group treated with B(a)P only. Following administration of B(a)P, GSH level decreased in brain and kidney. Melatonin in combination with B(a)P induced rises in the GSH level in liver and brain, as compared to the receiving B(a)P alone. The activity of SOD increased in the rats treated with melatonin alone but the highest activity was observed in rats treated with B(a)P plus melatonin. CAT activity in the melatonin-treated group increased in brain and liver. Similar to SOD, activity of the enzyme significantly increased in the group treated in combination with B(a)P and melatonin, as compared to the remaining groups in all tested tissues. The results suggest that melatonin protects cells from the damaging action of B(a)P. According to our knowledge, there are no studies describing the effects of melatonin on lipid peroxidation markers and antioxidative enzymes during intoxication of B(a)P in the brain, liver and kidneys. The results of present study give a perspective for further studies of its free radical scavenger properties in prevention of oxidative stress dependent diseases, among others cancers caused by carcinogens such as B(a)P.     

Cardiorespiratory regulation and activity patterns of rat pups studied with their mothers during the nursing cycle

Rat pups aged 10 to 19 days were implanted with chronic electrodes and recorded while freely moving in the litter situation, during nursing and throughout naturally occurring maternal absences. Heart rates were significantly higher in the mother's presence (p<.01) while respiratory rates and percent of time spent active were identical under the 2 conditions. Pups' inactive heart rates progressively increased during the 20 min of nursing, while no such time trends were evident in other measures. Inactive heart rates decreased significantly (p<.01) as a function of age; respiratory rates and activity during nursing showed similar trends. A histogram of number of periods of activity bursts of different durations while pups were nursing showed a preponderance of 1- to 5-sec bursts which were observed to be associated with active sucking and pawing movements. This pattern of short bursts of spontaneous activity was repeated almost identically when the mother was absent, although the behavior was qualitatively different. In a second experiment, increases in pups' body temperature of .2°C to 1.0°C were found to accompany active nursing. If such increases were imposed by an artificial heat source, heart rates of pups actually fell slightly. In a third study, heart rates were recorded from nursing mothers and found to be relatively unaffected by stimulation from the pups.     

Changes in cholinergic enzyme activities in the cuttlefish brain during memory formation

Cephalopods are promising invertebrate models to investigate the neurobiology of learning and memory due to their advanced behavioral abilities. In the present study, acetylcholine synthesis and catabolism were studied in various central nervous system (CNS) regions of cuttlefish subjected to associative learning procedures with different retention delays, with the aim of characterizing the involvement of cholinergic neurotransmission in learning and memory processes in this species. In the first experiment, the acquisition procedure consisted of a single continuous trial. As a response to a short retention delay (60 min), when compared to control or to a very short retention delay (2 min), cholinergic enzymatic activities decreased in structures involved in learning and memory (vertical-subvertical lobes) and in lower motor centers (brachial and pedal lobes). In the second experiment, the same learning paradigm was used but with repeated trials. In this case, a long-term retention (24 h) induced an increase in acetylcholine catabolism in the pedal and optic lobes (lower motor and higher centers, respectively) when compared to control. These results suggest the occurrence of different regulatory mechanisms of cholinergic enzymes as a response to memory formation with a long- or a short-term retention delay.     

Lysosomal enzyme activities during ageing of adult human liver cell lines

Ten lysosomal enzyme activities have been compared during the growth and ageing of adult human liver cell lines. Arylsulfatase A, beta-D-galactosidase and beta-D-glucuronidase activities were significantly lower and arylsulfatase B activity was significantly higher in senescent cells than in actively growing cells. Furthermore, hexosaminidase activity was lower and acid phosphatase activity higher in old cells in every cell line tested but the differences were not significant. On the other hand, no change occurred in alpha-L-fucosidase, alpha-D-mannosidase, alpha-D-galactosidase and alpha-D-glucosidase activities. These results demonstrate that the increase in size and number of secondary lysosomes during ageing is accompanied for a few lysosomal enzymes by an increase or a decrease in activity depending on the enzyme.     

Grief reactions of mothers of adolescents and young adults with traumatic brain injury.

One hundred and two mothers of adolescents and young adults with traumatic brain injury completed a modified Grief Experience Inventory (GEI) (Sanders, Mauger, & Strong, 1985) and rated their child's functioning on a modified Neurobehavioral Rating Scale (NRS) (Levin et al., 1987). More severe grief was reported by mothers who rated their children as having poor neurobehavioral functioning and by mothers of young adult rather than adolescent patients. The guilt component of grief varied significantly across the 3-year post-injury period measured in the study. Historical comparisons of these respondents with other bereaved populations showed that mothers of adolescent and young adults with head injury reported more intense grief than parents who had experienced other significant non-death losses.     

缺氧缺血性脑损伤新生大鼠脑干听觉诱发电位的动态变化

目的：探讨缺氧缺血性脑损伤新生大鼠脑干听觉诱发电位（BAEP）的动态变化。方法：30只出生13天的新生SD大鼠随机分为对照组和缺氧缺血组,每组15只。将出生后第13天新生大鼠结扎左侧颈总动脉后,置于含氧8％的低氧环境中3h建立缺氧缺血性脑损伤动物模型。出生后第14、20、27、37、47、57、67和77天检测大鼠的BAEP。结果：缺氧缺血组新生大鼠3h缺氧复氧1h后,表现为向左侧旋转,爬行时右侧后肢呈现拖步。出生后第14～47天缺氧缺血组大鼠BAEP波峰潜伏期（PL）和波峰间潜伏期（IPL）较对照组显著延长（P〈0．05或P〈0．01）,这些鼠的BAEP的PL及IPL均随年龄的增加而缩短,并且鼠可发育成熟。结论：缺氧缺血性脑损伤新生大鼠BAEP有显著的可逆性异常变化,其PL和IPL是动态监测与客观评价新生期缺氧缺血性脑损伤和听觉障碍的灵敏指标。     

Lysosomal enzyme activities in experimental granulomatous inflammation.

Foreign-body (dextran beads) and hypersensitivity (antigen-coupled agarose beads) lung granulomas were induced in BALB/c mice by the intratracheal injection of beads. Large granulomas developed, which reached peak intensity within 3 days and declined in size thereafter. Aqueous extracts of both granulomas contained high levels of lysosomal enzymes N-acetyl-beta-D-glucosaminidase (NAG) and lysozyme. Lysosomal enzyme activities in the extracts correlated with granuloma sizes. Dispersed granuloma cells were able to produce these enzymes. These results suggest that lysosomal enzymes may reflect the activity/size of granulomatous inflammation.     

Peroxisomal enzymes in normal and tumoral human breast.

The presence of peroxisomes and their enzymatic content were investigated and compared in healthy and neoplastic human breast epithelial cells using cytochemical studies at the ultrastructural level as well as Western blot and biochemical analyses. Ultrastructural cytochemistry revealed the presence of these organelles in both normal and neoplastic breast tissues. Their mean diameter was 0.27 +/- 0.11 micron. No significant difference was noted between numbers of peroxisomes in normal and neoplastic breast epithelia. Catalase, D-amino acid oxidase, and urate oxidase were found to be expressed in mammary carcinoma and in surrounding non-malignant tissue when the postnuclear supernatant fractions prepared from homogenates were assessed by Western blot techniques. Their specific activities and that of fatty acyl CoA oxidase as determined spectrophotometrically were found to be diminished in the tumour when compared with the control tissue. On the other hand, no significant difference was found in the specific activity of the L-alpha-hydroxy acid oxidase of normal and neoplastic human breast tissues. Investigations of the relationship between peroxisomal enzymes and tumour grade revealed that catalase, urate oxidase, and fatty acyl CoA oxidase activities in breast neoplastic tissues belonging to grade III were significantly lower than in the adjacent normal tissues.