Evidence of oxidative stress in peroxisomal disorders

<p><b>INTRODUCTION</b>Peroxisomal disorders are subdivided into peroxisome biogenesis disorders (PBDs) and single peroxisomal enzyme deficiency. Many peroxisomal diseases exhibit excessive oxidative stress, leading to neurological alterations and dysfunction. Peroxisomes use oxygen in oxidative reactions that generate hydrogen peroxide. This study aimed to investigate various oxidative stress parameters in patients suffering from peroxisomal disorders.</p><p><b>METHODS</b>A total of 20 patients with peroxisomal disorders, aged six months to 13 years (mean age 5.9 ± 3.2 years), were compared to 14 healthy controls. All individuals were subjected to full history-taking, including a three-generation pedigree analysis concerning parental consanguinity and similarly affected members in the family, with meticulous clinical examination to detect any malformation or anomaly. Estimation of very-long-chain fatty acids and phytanic acid was done to verify the diagnosis. Brain magnetic resonance imaging, electroencephalogram, visual evoked potential, auditory potential and plain radiography were conducted to assess the pathological condition of the patients. Oxidative stress parameters, including nitric oxide (NO), malondialdehyde (MDA) and superoxide dismutase (SOD), were estimated in both the patients and controls.</p><p><b>RESULTS</b>Significant increases in both MDA and NO were found in patients with PBDs. It was also demonstrated that SOD was significantly lower in patients with PDB than the controls.</p><p><b>CONCLUSION</b>This study sheds more light on the link between oxidative stress and peroxisomal disorders, as oxidative stress may be a hallmark of peroxisomal disorders. Consequently, one of the useful neuronal rescue strategies could be treatment with antioxidant agents in addition to other lines of treatments.</p>

Evaluation of the role of garlic on the structure of liver and gastric mucosa in aged male albino rat: a histological and histochemical study

Age related changes in the hepatic and gastric tissues have been discovered and are considered to be implicated in the pathogenesis of some diseases. To evaluate the effect of garlic as a prophylactic or a therapeutic tool against age related changes in the liver and stomach. 80 male albino rats were used. Classified into four groups: group 1: 15 rats served as control adult, group 2: 15 rats served as control aged, group 3: 25 adult rat treated with Tomax in a dose of 100 mg/kg orally daily till aging and group 4: 25 aged rats treated with Tomax in the same previous dose for 4 months. Animals were sacrificed and specimens from the liver and stomach were prepared for light and electron microscopy. Light and electron microscopic examination of liver and stomach of group 1 revealed the normal structure. Age related changes were detected in group 2 in the form of vacuolation of cells lining the gastric glands and disturbed hepatic architecture. Ultrastructurally, degenerative changes in parietal and chief cells were observed. Hepatocytes showed variable sized nuclei with marginated hetero chromatin clumps, areas of rarified cytoplasm, fragmented endoplasmic reticulum and interrupted cell membrane. Tomax treatment in group 3 greatly improved the aging changes in liver and gastric mucosa. Decreased vacuolation of gastric epithelial cells and restored hepatic architecture were observed. Ultrastructural degenerative changes were less pronounced in both tissues. In group 4 there was no obvious improvement but they were more or less similar to group 2. It could be concluded that garlic could be used as a prophylactic measure against age induced structural changes in the liver and stomach rather than being used as a therapeutic one

light and electron microscopic study of the effect of dehydroepiandrosterone sulfate on myocardium and adrenal zona reticularis of aged male albino rats

Aging is associated with a progressive decline of plasma levels of dehydroepiandrosterone [DHEA] and dehydroepiandrosterone sulfate [DHEAS]. The present work studied the effect of DHEAS administration on the age related histological changes in the myocardium of the heart [being implicated in increased death rate from cardiovascular diseases in the elderly] and in the adrenal zona reticularis [being the major source of DHEA and DHEAS secretion]. Thirty male albino rats were divided into three groups; ten animals each. Group I was the control adult group [6-months age], group II was the control aged group [24-months age], and group III was the treated aged group [24-months age] that received DHEAS orally in a dose of 0.05 mg/rat/day for one month. Specimens from the left ventricle of the heart and from the suprarenal gland were taken from all groups and prepared for light and electron microscopic examination. In control aged group, the myocardium exhibited disorganization of cardiac myocytes and an increase in collagen fibers. Many cardiac myocytes had deeply stained nuclei with increased heterochromatin. Their sarcoplasm showed variable staining intensity, ill defined cross striations, marked degeneration of the mitochondria and increased intermyofibrillar spaces. Other cardiac myocytes appeared relatively with more or less normal light and electron microscopic structure. The cells of adrenal zona reticularis of control aged animals showed irregularity and deeply stained nuclei, in addition to decreased frequency of mitochondria and accumulation of lipid droplets in their cytoplasm. After DHEAS administration, there was a marked reduction in the age related histological changes of both the myocardium and adrenal zona reticularis. The myocardium of DHEAS treated aged animals showed regular arrangement of cardiac myocytes with comparative decrease in appearance of collagen fibers compared to the control aged group. Many cardiac myocytes had relatively normal appearance of their nuclei and sarcoplasm with prominent cross striations, regular organization of myofibrils and less degenerative changes in the mitochondria compared to those of the control aged group. Most zona reticularis cells of DHEAS treated animals had rounded nuclei and relatively normal appearance of their cytoplasm with increased frequency of mitochondria and decreased content of lipid compared to those of the control aged group. The mechanism of action of DHEAS as an antiaging steroid has been discussed. The preventive effect of DHEAS against age related structural changes [although incomplete prevention] is promising of its use as replacement therapy in elderly people to prevent, delay or attenuate the cardiac disorders which accompany aging and to improve the enzymatic activities and endocrine function of adrenal zona reticularis, thus, promote improvement of health with aging

Association of insulin-like growth factor-1 [IGF-1], dietary intake and cognitive functions in normal school age children

Insulin-like growth factor I [IGF-I] is a hormone that mediates the effects of growth hormone and plays a critical role in somatic growth regulation and organ development. It is hypothesized that it also plays a key role in human brain development. The dietary determinants of circulating levels of components of the IGF system are of interest, as these may mediate some of the effects of diet on later health. However, few studies have examined the relationship between diet and IGF-1 levels in children, as well as the relationship between IGF-1 and mental development. To investigate the role of diet on levels of IGF-I and their relationships with measures of IQ in a group of healthy children. The study included 222 apparently healthy children [113 boys and 109 girls], their height for age and weight for age were between 10[th]-90[th] percentiles according to World Health Organization [WHO] growth standards, their age ranged 8-11 years and all were prepubescent. They were chosen randomly from primary schools located in urban Giza Governorate. Nutritional status was assessed by 24-hours dietary intake history and anthropometric measurements [weight, height]. Plasma IGF-1 was evaluated by radioimmu-noassay technique, growth hormone [GH] was determined by immuno-enzymatic assay. Intelligence quotient [IQ] was measured with the Arabic version of the revised-Wechsler Intelligence Scale for Children. Familial background was investigated through structured questionnaire. IGF-1 levels [mean +/- SD] were 142.6 +/- 43.3 ng/mL for girls and 139.4 +/- 39.6ng/mL for boys. GH level was within normal range. IQ scores [mean +/- SD] were 101.03 +/- 17.4 and 103.11 +/- 19.8 for boys and girls, respectively. IGF-1 levels were associated positively with IQ [r=0.81, p

Long chain polyunsaturated fatty acids and lipid profile in children with insulin dependent diabetes mellitus and their relation to lipid peroxidation

Type-1 diabetes is one of the major chronic illnesses during childhood. In this study, levels of glycosylated hemoglobin [HbA1], lipoproteins and the major groups of polyunsaturated fatty acids in plasma were studied in 30 diabetic patients and compared with 20 non diabetic children. Malondialdhyde, a lipid peroxidation end product was also assayed. In the present work, the parent essential fatty acid, lenoleic acid [LA] was found to be higher in the DM-1 patients than in controls. However, values of the long chain polyunsaturated fatty acids [LCPUFAs] namely [dohom-gamma-Linolenic acid C20:3w6 [DHGLA], arachidonic acid C20:5w6 [AA] and Docosapentanoic acid C20:5w6 [DPA], from omega 6 series as well as docosahexaenoic acid C22:6w3 [DHA] from omega 3 series in diabetic children were found to be significantly lower than non diabetics. This pattern of plasma PUFAs is compatible with a reduced conversion rate of the essential fatty acids [EFA] to their respective longer chain metabolites in DM-1 children. As regards lipoprotein pattern abnormalities could be found except for triglycerides levels. A positive correlation was found between Hb-A1 and each of cholesterol, LDL-C, HDL-C/Cholesterol, LDL-C/HDL-C and a reversed correlation was encountered between HbA1 and HDL-C. This result emphasizes the relation between poor metabolic control in hyperglycemic patients and increased CVD risk. There is an enhanced lipid peroxidation in DM-1 with affected plasma lipoproteins pattern. Under insulin insufficiency, there is reduced formation of long chain omega 6 PUFA from parent EFA together with a decreased level of omega-3 fatty acids

Withdrawal effect of codeine and phenobarbitone on the brain and cardiac function enzymes and glucose metabolism in adult albino rats

This study is to elucidate the withdrawal of codeine and phenobarbiton and their effects on some brain, cardiac activity and glucose-insulin-glucagone relations. This may help to clarify the side effect and metabolic changes which may occur as a result of drug administration. For this aim forty adult albino rats were randomly divided to 5 groups each of eight animals. First group was kept as control. Second and third group received codeine orally in therapeutic and double therapeutic dose. Forth and fifth group were given phenobarbiton intramuscular in therapeutic and double therapeutic dose. Drugs were administered day after day for four consecutive weeks. Alterations in serum Monoamine oxidase [MAO] activities, Cholinesterase [ChE] activities, whereas 5' nucleotidase [5'NT] and creatine kinase [CK] activity lactate dehydrogenase [LDH], Aspartat-aminotransferase [AST], glucose, insulin and glucagon were recorded. Such alterations were discussed in relation to doses and levels of drugs in urine of rats that actually stopped drug and exhibited that the analgesic effects symptoms of the drugs are expression of changes of functioning enzymes

Polyunsaturated fatty acids and lipid profile in asthmatic Egyptian Children

The profile of polyunsaturated fatty acids [PUFAs] as well as other lipid parameters were studied in 53 Egyptian children [32 males and 21 females], their ages ranged from 4-10 years. The children were divided into 2 groups: asthmatic group [n=33] and non asthmatic healthy group [n=20]. The asthmatic group was subdivided according to the new GINA guidelines into 2 groups: children with mild persistent asthma [n=16] and children with moderate and severe asthma [n=17]. Mean levels of both serum IgE and malondialdehyde showed significant increase in asthmatic children above that of the normal control children. Also, lipid profile showed significantly increased mean levels of each of total cholesterol, LDL, and phospholipids in asthmatics above those of the non asthmatic control group. However the results of triglycerides and HDL mean levels were almost similar to those of the control group. Although results of polyunsaturated fatty acids showed an increase in the mean level of omega 6 fatty acids [Linoleic and Arachidonic] in plasma of asthmatic children as compared to those of the non asthmatics, however, this increase was not significant [p=0.661]. On the other h and, omega 3 series mean levels were reduced in the asthmatic children as compared to those of the non asthmatics. The reduction was not significant [p=0.341] despite the significant reduction of docosahexaenoic acids alone. Ratios between total omega 6 [C18:2 6 + C20:4 6/total omega 3 [C18:3 3 + C22:6 3] as well as ratios between [C20:4 6]/C22:6 3] showed that the ratios were reduced for asthmatic children as compared to those of the non asthmatics; but the difference was not significant [p>0.05]. It is concluded from this study that Omega-6 fatty acids and Omega-3 fatty acids patterns may contribute to symptoms of asthma. So, dietary modification may help patients manage their asthma as well as improving their overall health. Moreover, in view of the current drug treatment regimes which are mainly palliative rather than curative, it appears logical to provide asthmatics with non-harmful approaches as an adjunct to their st and ard asthma care. Antioxidant supplementation may be a promising adjuvant therapy

Histological and immunohistochemical studies of effect of fenugreek seeds on the pituitary, mammary glands and ovary of lactating rabbits

The present work was done to study the effect of fenugreek seeds on the structure of the pars distalis, ovary and mammary gland of lactating rabbit. A total number of 24 lactating rabbits was used. The animals were divided into two groups. One served as a control lactating group [8 rabbits] and the other group was lactating rabbits treated with the seeds [16 rabbits]. The control and treated rabbits were sacrificed after two weeks and four weeks. Specimens of the pituitary gland were prepared for electron microscopy [E/M]. Mammary gland was prepared for light and electron microscopy while the ovary was prepared for light microscopy. Another specimens of the pituitary, mammary glands and ovary were prepared and processed for immunohistochemical application of mouse monocolonal prolactin [PRL] receptor antibody to detect the prolactin receptors in these tissues. This study cleared that, there was apparent increase in the number, size and signs of activity of mammotrophs. The mammary gland showed an increase in the activity of the alveolar cells and in the amount of milk secretion. As regard the ovary, there was an apparent increase in the number of primary follicles. There was progressive increase in the amount of atretic follicles. Corpus luteum showed progressive decrease in size and degeneration. The number of healthy growing follicle was reduced. The immunohistochemical study demonstrated a progressive increase in the number and size of mammotrophs that showing positive reaction for PRL receptor antibody. The mammary gland showed positive reaction in the alveolar cells and in the stroma cells. The ovary showed strong positive reaction for PRL receptor antibody. It becomes obvious that the treatment with fenugreek seeds leads to stimulation of the mammotrophs and mammary gland. At the same time it causes suppression of the ovary. In conclusion, the use of fenugreek seeds has a double advantageous effects as its ingestion by lactating females increases the milk production and in the mean time it suppresses the ovary which may decrease the possibility of pregnancy during lactation. So, we recommend the use of fenugreek seeds instead of the hormones or chemical drugs for more milk production and as a partial ovulation inhibitor

Nutritional stunting in Egypt: which nutrient is responsible?

We looked at the relationship between linear growth retardation and deficiencies of certain nutrients in Egyptian children. A group of 107 stunted children aged between 10 and 18 years were subjected to history-taking, physical examination and laboratory investigations. Selected cases were referred to radiology for assessment of bone age. Thirty-nine children were enrolled as controls. Serum haemoglobin, alpha-tocopherol, retinol and magnesium levels were significantly decreased in stunted children compared with the controls. Serum zinc levels were also lower in the stunted group but not significantly so. We conclude that several nutrient deficiencies occur simultaneously in stunted children and all of them may be responsible for stunting

Biochemical and histological effects of verrucarin Y-toxin on adult male mice liver

The aim of the present work was to evaluate the effects of verrucarin J-toxin on serum biochemistry and on light and electron microscopic structures of the liver of adult male mice. Treated mice was injected intraperitonealy by toxin in a single dose of 0.9 mg/kg [group A] and 0.5 mg/kg body weight [group B]. The animals were sacrificed after 2, 4, 6 weeks [10 each] and compared to toxin free control [C] group. Results indicated that glucose level was significantly different in the treated groups [A, B], which were injected for 2 and 4 weeks than control [C] group. But there was no significant difference in 6 weeks. Plasma levels of triglycerides or cholesterol were significantly higher in both treated mice than control. Many histological changes occurred in the liver cells of both treated groups [A and B] after 2 and 4 weeks. The hepatocytes were engorged with glycogen. The nuclei and cell organelles are markedly affected. After 6 weeks from treatment many hepatocytes were, somewhat similar to the control

Effect of nigella sativa seed's oil on alloxan induced diabetic rats a histological study on pancreatic beta cells

In order to evaluate the potential effect of Nigella sativa seed's oil [NSO] on experimentally induced diabetes, alloxan was injected intra- muscularly in a single dose of 175 mg/kg in adult male albino rats. A group of animals was kept diabetic for fifteen days, another group for three months and a third group was injected with alloxan then after four days were treated daily with NSO for fifteen days. A fourth group was treated with NSO after three months of alloxan injection. The fifth group was kept as control. Alloxan caused degranulation and massive destruction of beta cells, especially after three months of diabetes induction. Treatment of early stage of diabetes [after four days of alloxan injection] with NSO prevented the subsequent changes by alloxan. NSO had no role in the treatment of chronic diabetes [at late stage]. As regard these findings, the anti-diabetic effect of NSO was clearly observed only in the treatment of early stage of diabetes rather than after three months of the diseases. It was concluded that the anti- diabetic effect of NSO may be through its protective effect on beta cells, especially in early stage of the disease

Chronic toxic effect of plant growth promoting hormone, gibberellic acid, on the liver cells of adult male albino rat

Gibberellic acid is one of the plant growth promoting hormones that is used in agriculture to increase the growth of fruits and vegetables. The toxic effect of chronic oral exposure to this growth promoter on the histological structure of liver cells of rats was investigated into three groups, each was 12 rats. The first group received a daily oral dose of 70 mg/kg of gibberellic acid dissolved in distilled water for one month then animals were sacrificed. The second group received the same dose of gibberellic acid for one month then animals were left to recover and were sacrificed after two months from the last dose. The third group of animals served as controls and received a daily oral dose of distilled water. Liver specimens were taken from animals of each group, prepared for and examined by light and electron microscopes. The significant histological changes in the liver cells after exposure to gibberellic acid were presented in the form of swelling of the majority of cells, depletion of glycogen, appearance of large amounts of smooth endoplasmic reticulum, appearance of large areas of rarified cytoplasm separating dense areas of cellular organelles, increased of lysosomes, swelling and degeneration of many cells. Following substance withdrawal, a few cells became nearly similar to those of the controls, while the majority of cells remained affected. These data supported the deleterious effects of gibberellic acid on the liver after chronic oral exposure and the recovery from these effects might need a longer time. So, the need for protection from the hazards of these substances should be searched for and continued

Ultrastructural study on the duct system of the submandibular gland of adult control and experimentally diabetic male albino rat

The fine structure of the submandibular gland of male adult albino rats has been examined in control and in rats subjected to induced diabetes for one, two and four months. The ultrastructure of submandibular gland of control rats was thoroughly described. Certain observations were recorded for the first time in rats, such as the presence of a special type of cells in the intercalated duct under the name clear cells [primitive cells]. The lining of the striated and granular ducts were focussed upon. All diabetic rats developed persistent hyperglycemia, lost weight, had atrophied testes and some of them became cachectic. Variable ultrastructural changes were evident in the affected submandibular components even in early stages of diabetic induction of the experiment. It became more progressive after four months of induced diabetes. The duct system of the gland showed the prevalence of granular cells on the expense of clear cells among the lining epithelium of intercalated duct, degranulation of the lining cells of granular convoluted tubule and their atrophy after four months of treatment. The general architecture of the striated ductal cells was disrupted, the basal enfoldings of the plasma membrane became indistinct and the cytoplasm showed vacuoles which compressed the nucleus and organelles

Effect of topical levobunolol on plasma lipids

This study was designed to evaluate the effect of topical levobunolol 0.5% [non selective beta blocker] on plasma lipid levels. Fifteen glaucomatous patients not using any medications known to alter the plasma lipid levels, non diabetic or obese were selected. These patients used topical levobunolol 0.5% in both eyes twice daily for treatment of glaucoma for three months, they were subjected to measurements of their IOP. C/D ratio, heart rate, blood pressure, body weight and fasting plasma lipid levels before treatment and monthly for three months. We found that, topical levobunolol 0.5% is effective in controlling IOP but on the other hand there was a 50% increase in triglycerides. 20% decrease in high density lipoprotein, 15% increase in total lipids while there were no significant changes in total cholesterol and low density lipoprotein. These changes are known to increase the risk of coronary heart disease and shift the patients to the high risk category