Renal damage induced by uranyl nitrate and oestradiol-17beta in Japanese quail and Wistar rats

Morphological alterations occurred in the kidneys of Japanese quail and Wistar rats 18 h after giving uranyl nitrate solution i.v. Dosages of 50 micromol U/kg body weight produced more extensive and more severe damage than did 0.15 micromol U/kg. Degeneration and necrosis of tubular epithelium was prominent in the proximal tubules in rats and in the distal tubules in quail. Less extensive damage occurred in glomeruli and collecting ducts. Protein deposits were seen in the kidneys of both rats and quail. Calcification of degenerating epithelial cells, calcified casts in the tubules, and damage to collecting ducts were seen in quail but not in rats. Oestradiol-17beta (160 micromol/kg body weight, i.m.) induced renal lesions in quail but not in rats. Quail and rat renal lesions induced by the combination of oestradiol plus uranium were more severe than lesions induced by either toxicant singly.     

Effect of (+)-cyanidanol-3 on rat brain lipid peroxidation.

Non-enzymic lipid peroxidation was stimulated in homogenates, plasma membrane fractions and microsomes of rat brain in vitro by incubation with ascorbic acid. Malondialdehyde formation was determined by the thiobarbituric acid test. It has been established that (+)-cyanidanol-3 inhibits the ascorbic acid-stimulated lipid peroxidation in various fractions of rat brain. On the basis of these results it is suggested that (+)-cyanidanol-3 treatment protects brain suspensions against lipid peroxidation by acting as a free radical scavenger in vitro.     

Effect of (+)-cyanidanol-3 on rat brain lipid peroxidation

Non-enzymic lipid peroxidation was stimulated in homogenates, plasma membrane fractions and microsomes of rat brain in vitro by incubation with ascorbic acid. Malondialdehyde formation was determined by the thiobarbituric acid test. It has been established that (+)-cyanidanol-3 inhibits the ascorbic acid-stimulated lipid peroxidation in various fractions of rat brain. On the basis of these results it is suggested that (+)-cyanidanol-3 treatment protects brain suspensions against lipid peroxidation by acting as a free radical scavenger in vitro.     

Acute effect of aspartame-induced oxidative stress in Wistar albino rat brain

The present study was carried out to investigate the acute effect of aspartame on oxidative stress in the Wistar albino rat brain. We sought to investigate whether acute administration of aspartame (75 mg/kg) could release methanol and induce oxidative stress in the rat brain 24 hours after administration. To mimic human methanol metabolism, methotrexate treated rats were used to study aspartame effects. Wistar strain male albino rats were administered with aspartame orally as a single dose and studied along with controls and methotrexate treated controls. Blood methanol and formate level were estimated after 24 hours and rats were sacrificed and free radical changes were observed in discrete regions by assessing the scavenging enzymes, reduce dglutathione (GSH), lipid peroxidation and protein thiol levels. There was a significant increase in lipid peroxidation levels, superoxide dismutase activity (SOD), glutathione peroxidase levels (GPx), and catalase activity (CAT) with a significant decrease in GSH and protein thiol. Aspartame exposure resulted in detectable methanol even after 24 hours. Methanol and its metabolites may be responsible for the generation of oxidative stress in brain regions. The observed alteration in aspartame fed animals may be due to its metabolite methanol and elevated formate. The elevated free radicals due to methanol induced oxidative stress.     

Vascular damage and lipid peroxidation in choline-deficient rats

Dietary butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) protected rats against the vascular damage of acute choline deficiency. The protection was not due to decreased food intake or lower body weight in the animals fed the antioxidants. Dietary vitamin E supplementation did not protect against vascular damage. Free radical concentrations were higher in the liver, heart and kidneys of choline-deficient rats than in those of controls, but differences were small and variation was great. Thiobarbituric acid-reactive material (TBA) was consistently higher in livers of choline-deficient rats than in those of controls, but values were dependent on and inversely proportional to dietary levels of vitamin E. Conversely, TBA levels were high in livers of rats fed the BHA- and BHT-supplemented, choline-deficient diet. Therefore, hepatic TBA values did not always correlate with the extent of vascular damage. Diene conjugation was not detected in hepatic lipids of choline-deficient rats during the first 48 hr, but was found consistently after 10 days. The occurrence of diene conjugation in hepatic lipids was related directly to the incidence and severity of vascular damage.     

Melatonin and vitamin E limit nitric oxide-induced lipid peroxidation in rat brain homogenates

We have investigated the level of lipid peroxidation (LPO) in rat brain homogenates in the presence of nitric oxide (NO) which was released by the addition of sodium nitroprusside (SNP) and compared it with that induced by H₂O₂. We also examined the effect of melatonin and vitamin E on the NO-induced LPO. The concentration of malonaldehyde (MDA) plus 4-hydroxyalkenals (4-HDA) was used as an index of LPO. While both H₂O₂ and SNP increased MDA+4-HDA production in brain homogenates in a concentration-dependent manner, SNP was more potent than H₂O₂ at all concentrations tested. Both melatonin or vitamin E reduced NO-induced LPO in a dose-dependent manner in concentrations ranging from 10 μM to 10 mM. Under the in vitro conditions of this experiment, vitamin E was more efficient than melatonin in limiting NO-induced LPO in rat brain homogenates.     

Effects of hyperbaric oxygen on lipid peroxidation and content of phospholipids in rat brain

Exposure to absolute oxygen pressure of 3 and 5 bar revealed hemispheric and interhemispheric differences in lipid peroxidation and the content of phospholipids in rat brain. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 128, No. 9, pp. 261–263, September, 1999     

Effect of cerebronorm on energy metabolism and lipid peroxidation in rat brain during hypoxia

Cerebronorm prevents de-energization of mitochondria, limitation of succinate-and NAD-dependent energy production, and oxidation-phosphorylation uncoupling and inhibits LPO processes in the brain of rats under conditions of hypoxia. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 144, No. 11, pp. 538–541, November, 2007     

Measurement of lipid peroxidation products in rabbit brain and organs (response to aluminum exposure)

A method was developed for measuring the concentration of lipid peroxidation products in rabbit brain, heart, lung, liver, and kidney tissue. Specimens were homogenized in cold buffer, acidified, and heated to near boiling in the presence of thiobarbituric acid in order to form the malondialdehyde-thiobarbiturate adduct. After centrifugation, the supernatant was injected onto a reversed-phase high pressure liquid chromatography (HPLC) column, and the effluent was monitored for absorbance at 532 nm. Absorbances were compared to a standard curve constructed from absorbance data for tetraethoxypropane standards, which yield stoichiometric amounts of the malondialdehyde-thiobarbiturate adduct. Results were expressed as nmol of adduct per gram (dry weight) of tissue. Hippocampus had significantly greater concentrations of lipid peroxidation products (79.0 +/- 15.7 nmol per g) than did brainstem (52.1 +/- 13.8 nmol per g), but there was no significant increase in lipid peroxidation in aluminum treated rabbit brains when compared with controls. Aluminum intoxication appeared, however, to stimulate lipid peroxidation in heart, lung, liver, and kidney. Aluminum accumulation in brain and organ tissue of treated rabbits was confirmed by atomic absorption spectrophotometry of an acid digest of the homogenate. These results are in contrast to previous studies which demonstrated an increase in lipid peroxidation products in rat brains following oral administration of aluminum hydroxide.     

Immunohistochemical detection of the lipid peroxidation product 4-hydroxynonenal after experimental brain injury in the rat.

This study examined the accumulation of the cytotoxic lipid peroxidation product 4-hydroxynonenal (HNE) after lateral fluid percussion (FP) brain injury in rats. A diffuse distribution of HNE-immunoreactivity (HNE-ir) was observed in the cortex and hippocampus of the ipsilateral, but not of the contralateral, hemisphere at 30 min, 6 h, 24 h, and 48 h after brain injury. The HNE-ir was well-localized in cell bodies of the ipsilateral cortex and the CA3 pyramidal layer in the ipsilateral hippocampus. Because HNE's interaction with certain proteins causes protein dysfunction and HNE, in vitro, causes neuronal cell damage, the present results suggest that HNE's interaction with neuronal proteins may contribute to neuronal damage in the ipsilateral cortex and hippocampus after brain injury.     

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced lipid peroxidation and DNA damage in mouse bone marrow and blood

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin that induces Parkinsonism in humans, monkeys, and mice and oxidative stress in mammalian cells and tissues. In the present study, the relationship between the generation of lipid peroxidation products and DNA damage was studied in mice treated with MPTP. The frequency of micronucleated polychromatic erythrocytes (MN-PCE) and the concentrations of malonaldehyde and 4-hydroxyalkenals were determined in the bone marrow and peripheral blood of mice 0, 24, 48, 72, and 96 hr after treatment with MPTP, cyclophosphamide as a positive control, or diluent. Both MN-PCE and the lipid peroxidation products increased in MPTP-treated mice, with significant levels being detected in bone marrow starting at 24 hr after treatment and in blood starting at 48 hr after treatment. These results suggest that the generation of oxidative products is related to the DNA damage produced by MPTP in mice.     

Inhibition of lipid peroxidation in synaptosomes from rat brain by peptide and protein fraction isolated from fetal human brain

Peptide and protein fractions isolated from fetal human brain inhibit with different efficiency nonenzymatic lipid peroxidation in synaptosomes from rat brain. These fractions reciprocally capture the superoxide anion radicals generated in the reaction of 6-hydroxydopamine autooxidation. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 122, No. 8, pp. 233–235, August, 1996     

Protective effect of melatonin and pinoline on nitric oxide-induced lipid and protein peroxidation in rat brain homogenates

Nitric oxide (NO) is a physiological neurotransmitter, a mediator of the excitatory neurotransmitter glutamate pathways that regulates several neuroendocrine functions, but excessive NO is toxic by itself and it interacts with superoxide radical (O(2)(-)) to form the peroxynitrite anion (ONOO(-)). Using rat brain homogenates, we investigated the effects of melatonin and pinoline in preventing the level of lipid peroxidation (LPO) and carbonyl contents in proteins induced by nitric oxide (NO) which was released by the addition of sodium nitroprusside (SNP). Lipid and protein peroxidation were estimated by quantifying malondialdehyde (MDA) and 4-hydroxyalkenal (4-HDA) concentrations and carbonyl contents, respectively. SNP increased MDA+4-HDA and carbonyl contents production in brain homogenates in a time and concentration dependent manner. Both, melatonin and pinoline reduced NO-induced LPO and carbonyl contents in a dose-dependent manner in concentrations from 0.03 to 3 mM and 1 to 300 microM, respectively. Under the in vitro conditions of this experiment, both antioxidants were more efficient in limiting SNP protein oxidation than lipid damage.     

Effects of S-adenosyl-L-methionine on lipid peroxidation and glutathione levels in rat brain slices exposed to reoxygenation after oxygen-glucose deprivation.

We analyzed the effects of S-adenosyl-L-methionine (AdoMet) on tissue oxidative stress in rat brain slices exposed to reoxygenation after oxygen-glucose deprivation. The thiobarbituric acid reactive substances (TBARS), total and oxidized glutathione, and lactate-dehydrogenase efflux (LDH) from tissue to the incubation medium, were measured. Brain slices were incubated without glucose and with N2, then glucose was added and O2 was perfused. After the anoxic-reoxygenation period, increase in TBARS, oxidized glutathione and LDH efflux, and decrease in total glutathione levels, were observed. The incubation with AdoMet before the anoxic period reduced TBARS (31-1000 micromol/l), glutathione production was increased (31-1000 micromol/l), LDH efflux decreased 6.41% with 15 micromol/l and 61.5% with 500 micromol/l). In the ex vivo experiments, we administered 50 mg/kg per day p.o., AdoMet for 3 days, then brain slices were collected and the anoxia-reoxygenation experiment was carried out. AdoMet led to the inhibition of brain lipid peroxidation and increased total glutathione production, after 3 h-reoxygenation. The increase of LDH efflux in non-treated rats was reduced by 77%. We conclude that AdoMet exerts citoprotective effects in an experimental model of brain slices reoxygenation after oxygen-glucose deprivation.     

Inhibition of lipid peroxidation and protein oxidation by endogenous and exogenous antioxidants in rat brain microsomes in vitro

Parkinson's disease (PD) is characterized by the selective loss of dopaminergic (DAergic) neurons in the substantia nigra and the subsequent depletion of dopamine (DA). This study assessed the protective effects of costunolide on DA-induced apoptosis in human DAergic SH-SY5Y cells, and its regulation of DA metabolism-associated gene and protein expression. Annexin V and propidium iodide (PI) staining using flow cytometric analysis (FACS) revealed that costunolide significantly protected human DAergic SH-SY5Y cells against DA-induced apoptosis. In addition, co-treatment of costunolide with DA in SH-SY5Y cells regulated DA metabolism-associated gene expression, as we observed an increase in both mRNA and protein levels of nuclear receptor related-1 (Nurr1), DA transporter (DAT), and vesicular monoamine transporter type 2 (VMAT2). In contrast, α-synuclein (ASYN) protein levels were decreased. Our findings suggest that costunolide has anti-apoptotic activity, presumably due to its regulatory effects on DA metabolism-associated genes. Therefore, costunolide could be considered as a candidate therapy for the treatment of Parkinson's disease.     

Selective inhibition of lipid peroxidation in the brain during stress

Research Institute of General Pathology and Pathological Physiology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR G. N. Kryzhanovskii.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 106, No. 11, pp 542–544, November, 1988.     

Endrin-induced histopathological changes and lipid peroxidation in livers and kidneys of rats, mice, guinea pigs and hamsters.

Endrin toxicity may be due to an oxidative stress associated with increased lipid peroxidation, decreased glutathione content, and inhibition of glutathione peroxidase activity. Extensive interspecies variability exists in sensitivity towards endrin. Therefore, histopathological changes and lipid peroxidation in the livers and kidneys of rats, mice, hamsters, and guinea pigs were examined 24 hr after the administration of 4 mg endrin/kg body weight orally in corn oil. Degeneration and necrotic changes with inflammatory cell infiltration were observed in livers and kidneys, and interspecies variability occurred. Fatty changes in the form of hepatic foam cells with cytoplasmic vacuolation were present. Lipofuscin pigments, associated with lipid peroxidation, were observed in hepatocytes and Kupffer cells. These histopathological conditions were prevented in rats which had been pretreated with butylated hydroxyanisole, vitamins E and C, or cysteine, antioxidants and free radical scavengers which have previously been shown to inhibit lipid peroxidation. The extent of endrin-induced lipid peroxidation correlated well with the degree of histopathological changes. Thus, histological changes consistent with the induction of an oxidative stress were observed following the administration of endrin to various animal species.