ABSTRACT
Chronic alcohol ingestion is known to increase the generation of reactive oxygen species (ROS), thereby leading to liver damage. Antioxidant enzymes act individually or in combination to reduce or counter the effect of these ROS. Chronic administration of alcohol at (40% v/v, 1 ml/100 g), for 6 weeks showed a significant (p<0.05) elevated levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TB). There was also a significant (p<0.05) decreased levels of catalase, glutathione peroxidase, glutathione reductase and superoxide dismutase compared to control rats. Pre-treatment of rats with 200, 400 mg/kg body weight of aqueous leaf extract of Ziziphus mauritiana or 100 mg/kg silymarin resulted in a significant (p<0.05) decreased levels of ALT, AST, ALP, and TB with levels of catalase, glutathione peroxidase, glutathione reductase and superoxide dismutase showing a significant (p<0.05) increase compared to group administered alcohol only. Histopathology of rat liver administered with alcohol only resulted in severe necrosis, mononuclear cell aggregation and fatty degeneration in the central and mid zonal areas which was a characteristic of a damaged liver. Pre-treatment with the aqueous extract of Ziziphus mauritiana or silymarin reduced the morphological changes that are associated with chronic alcohol administration. The presence of tannins, saponins and phenolic compounds observed in the plant extract could be responsible for the observed effects of decreasing the levels of injured tissue marker and lipid peroxidation.
ABSTRACT
Chronic alcohol ingestion is known to increase the generation of reactive oxygen species (ROS); thereby leading to liver damage. Antioxidant enzymes act individually or in combination to reduce or counter the effect of these ROS. Chronic administration of alcohol at (40v/v; 1ml/100g); for 6 weeks showed a significant (p0.05) elevated levels of alanine aminotransferase (ALT); aspartate aminotransferase (AST); alkaline phosphatase (ALP); and total bilirubin (TB). There was also a significant (p0.05) decreased levels of catalase; glutathione peroxidase; glutathione reductase and superoxide dismutase compared to control rats. Pretreatment of rats with 200; 400 mg/kg body weight of aqueous leaf extract of Ziziphus mauritiana or 100 mg/kg silymarin resulted in a significant (p0.05) decreased levels of ALT; AST; ALP; and TB with levels of catalase; glutathione peroxidase; glutathione reductase and superoxide dismutase showing a significant (p0.05) increase compared to group administered alcohol only. Histopathology of rat liver administered with alcohol only resulted in severe necrosis; mononuclear cell aggregation and fatty degeneration in the central and mid zonal areas which was a characteristic of a damaged liver. Pre-treatment with the aqueous extract of Ziziphus mauritiana or silymarin reduced the morphological changes that are associated with chronic alcohol administration. The presence of tannins; saponins and phenolic compounds observed in the plant extract could be responsible for the observed effects of decreasing the levels of injured tissue marker and lipid peroxidation
Subject(s)
Antioxidants , Ethanol , Rats , ZiziphusABSTRACT
Four week old male Wistar rats were used to study the effects of scopoletin and cyanide on the histopathology of rat brain. The rats were divided into a control and three experimental groups (2-4) and fed rations containing 0.07 microg scopoletin/100 g, 0.07 microg scopoletin + 1.8 mg cyanide/100 g and 1.8 mg cyanide/100 g, respectively. These levels of scopoletin and cyanide corresponded to levels found in a processed cassava diet. The first group was fed the same ration as the others but without scopoletin and cyanide. The rats were fed these rations for twelve months. Rats from each group were sacrificed at the third, sixth, ninth and twelfth months; the relative brain weight of the rats (% of body weight) and histology of their brains were studied. The lipid peroxide levels of the rat brains were also studied at the twelfth month. The results showed that the relative brain weights of the rats fed scopoletin + cyanide were significantly (p<0.05) less than that of the control from the third month. There were no significant changes in the lipid peroxide levels of the rat brains in the various groups. Histological examination of the brains of the rats suggested that scopoletin is involved in the pathogenesis of the neuropathy seen in cassava consuming populations.
Subject(s)
Brain Diseases/chemically induced , Brain/drug effects , Cyanides/pharmacology , Scopoletin/pharmacology , Animals , Body Weight , Brain/metabolism , Brain/pathology , Brain Diseases/metabolism , Brain Diseases/pathology , Cyanides/adverse effects , Edema , Lipid Peroxidation , Male , Manihot/adverse effects , Necrosis , Organ Size , Rats , Rats, Wistar , Scopoletin/adverse effectsABSTRACT
A comparative study of the in vitro effects of the coumarin compounds, scopoletin and aflatoxin B1 (AFB1), on bovine (Bos indicus) hepatic mitochondrial respiration was carried out polarographically, using isocitrate -NAD+ (3 - site), succinate (2 - site), and reduced cytochrome c (1 - site), as respiratory substrates. Both scopoletin and AFB1 elicited a substrate--dependent stimulation or inhibition of the mitochondrial states 4 and 3 respiration. The results suggest that AFB1 has a higher tendency to inhibit the mitochondrial respiration than scopoletin, while scopoletin showed higher uncoupling effects than AFB1. The effects of scopoletin and AFB1 on mitochondria were more pronounced on the electron transport than on phosphorylation reaction. The extent (3-35%) of AFB1 induced inhibition of bovine mitochondrial respiration observed in this study, was appreciably lower than the values indicated in other animal species (rats and guinea fowls) reported in previous studies using equivalent concentrations of the toxin. These results were discussed in terms of the susceptibility of the animal species to the toxic effects of scopoletin and AFB1.
Subject(s)
Aflatoxin B1/pharmacology , Mitochondria, Liver/metabolism , Oxygen Consumption/drug effects , Scopoletin/pharmacology , Animals , Calcium/metabolism , Calcium/pharmacology , Cattle , Cytochrome c Group/metabolism , Isocitrates/metabolism , Mitochondria, Liver/drug effects , Mitochondrial Swelling/drug effects , NAD/metabolism , Polarography , Succinates/metabolismABSTRACT
Histoplasma capsulatum var. duboisii is the etiological agent of African histoplasmosis, an important deep mycosis in West Africa. Not much is known about the physiological properties of this fungus. This communication reports on the extracellular proteolytic enzyme activity of this fungus. Five isolates of this fungus tested hydrolyzed azocasein and bovine serum albumin at pH 6.8 and 8.0. Assay of the crude enzyme showed that proteolytic activity increased with age and peaked on the 10th day and then again on the 13th day for the yeast form, and on the 11th day of growth for the mycelial form. The optimum temperature and pH for maximum enzyme activity were 35 degrees C and 6.8 respectively. The proteinase activity was more pronounced with the yeast form than with the mycelial form. The action of enzyme inhibitors suggested the presence of an aspartyl proteinase.
Subject(s)
Endopeptidases/metabolism , Histoplasma/enzymology , Animals , Caseins/metabolism , Cattle , Culture Media , Hydrogen-Ion Concentration , Protease Inhibitors/pharmacology , Serum Albumin, Bovine , Temperature , Time FactorsABSTRACT
The plasma cholesterol and phospholipid levels as well as the bleeding time of chicks treated with single oral doses of scopoletin (60 micrograms/kg, body wt) and aflatoxin B1 (50 micrograms/kg, body wt) were measured at intervals for a period of one week (168 h). Both compounds generally increased the bleeding time (AFB1 0.8-28.7%, Scopoletin 0.5-38.2%), serum total and free cholesterol, and the serum phospholipid levels but decreased the levels of the serum esterified cholesterol fraction relative to control throughout the period of study. The extent of these changes elicited by the respective compounds and the variation in the differences between their respective effects varied with the measured parameters. The importance of the similarities in the effects elicited by aflatoxin B1 and Scopoletin was highlighted.
Subject(s)
Aflatoxin B1/pharmacology , Blood Coagulation/drug effects , Cholesterol/blood , Phospholipids/blood , Scopoletin/pharmacology , Administration, Oral , Aflatoxin B1/administration & dosage , Animals , Bleeding Time , Chickens , Male , Scopoletin/administration & dosageABSTRACT
Scopoletin has been isolated and identified in gari, a cassava food consumed in Nigeria (West Africa). Its levels in gari and cassava flour is not altered by post processing treatments such as sundrying, refrigeration and storage. Scopoletin has also been identified as an active principle in the traditional herbal infusion of the fruit of Tetrapleura tetraptera TAUB used in the ethnopharmacology of West Africa. It is a potent hypotensive and non-specific spasmolytic agent. These pharmacological effects of Scopoletin are probably the underlying factors in the slowly developing tropical neuropathy characterised by optic atrophy, nerve deafness and ataxia endemic among populations subsisting on cassava diets such as gari. Hitherto, these toxicities were attributed to cyanogenic glucosides (cyanide) present in cassava.
Subject(s)
Coumarins/analysis , Manihot/chemistry , Scopoletin/analysis , Coumarins/chemistry , Food Handling , Humans , Molecular Structure , Scopoletin/adverse effects , Scopoletin/chemistryABSTRACT
The activity level of acetylcholinesterase in the erythrocytes of 32 patients homozygous for sickle cell anemia was determined and compared with that of normal AA controls as well as with that of AS individuals. Acetylcholinesterase activity was markedly higher in erythrocyte membrane from SS individuals than in those from AS individuals or AA controls. Additionally, ATPase activities were also significantly higher in sickle cell erythrocytes as compared to normal cells. These higher values of acetylcholinesterase and ATPase activities in SS erythrocytes may be explained as a consequence of the abnormally high cation levels in sickle cell erythrocytes.
Subject(s)
Acetylcholinesterase/blood , Adenosine Triphosphatases/blood , Anemia, Sickle Cell/enzymology , Erythrocyte Membrane/enzymology , Anemia, Sickle Cell/blood , Cations, Divalent/blood , Humans , Sickle Cell Trait/enzymologyABSTRACT
The interactions of aflatoxin B1 (AFB1) with vitamin K, phenylbutazone, and sulfamethoxine were investigated in albino rats. Vitamin K (5 mg/kg) was able to completely suppress the increase in whole blood clotting time caused by AFB1 (25 micrograms/kg). Phenylbutazone (50 mg/kg) and sulfamethoxine (50 mg/kg) also significantly (P less than 0.05) lowered the increased clotting time caused by AFB1. Equilibrium dialysis was performed on rat plasma (4 mg/ml protein content) to investigate the displacement of AFB1 (3 micrograms) from its bound form by vitamin K (250 micrograms), phenylbutazone (2500 micrograms), and sulfamethoxine (2500 micrograms). Phenylbutazone and sulfamethoxine significantly (P less than 0.05) displaced AFB1 from rat plasma protein. Histopathological examinations performed on the liver, kidneys, and spleen of control and treated rats showed that none of the drugs used appeared to offer any significant organ protection against AFB1 except in the spleen.
Subject(s)
Aflatoxins/metabolism , Phenylbutazone/metabolism , Sulfameter/metabolism , Sulfanilamides/metabolism , Vitamin K/metabolism , Aflatoxin B1 , Aflatoxins/pharmacology , Animals , Blood Coagulation/drug effects , Carrier Proteins/metabolism , Drug Interactions , Female , Male , Phenylbutazone/pharmacology , Rats , Sulfameter/pharmacology , Vitamin K/pharmacologyABSTRACT
Red blood cells from 31 patients with sickle cell anemia whose hemoglobins were ascertained as SS were assayed for Mg-, Ca-, Na-, and total ATPase activities. The ATPase activities were correlated with the various stages of severity in each patient as determined by clinical parameters. The results demonstrate that increases in ATPase activities were associated with increases in the percentage severity of sickle cell anemia. Severity correlated inversely with fetal hemoglobin levels in the sickle cell patients. ATPase activities were generally higher in SS genotypes than in AS and AA normal individuals.
Subject(s)
Adenosine Triphosphatases/blood , Anemia, Sickle Cell/enzymology , Erythrocyte Membrane/enzymology , Anemia, Sickle Cell/blood , Fetal Hemoglobin/analysis , HumansABSTRACT
Aflatoxins B1, B2, G1, G2, and M1 have been evaluated for activity toward cytochrome oxidase in isolated rat liver mitochondria employing ferrocytochrome c and p-phenylene diamine as reductants. The aflatoxins inhibited the cytochrome oxidase activity to a greater extent when monitored by O2 uptake measurements than by substrate oxidation. AFG2 and AFM1 were the most potent (50-70%). Using oligomycin and 2,4-DNP as respiratory inhibitor and uncoupler, respectively, the aflatoxins appear to inhibit e- rather than energy transfer reactions. These toxins did not uncouple cytochrome oxidase activity.
Subject(s)
Aflatoxins/pharmacology , Electron Transport Complex IV/antagonists & inhibitors , Mitochondria, Liver/enzymology , Aflatoxins/isolation & purification , Animals , Kinetics , Male , Rats , Rats, Inbred Strains , Structure-Activity RelationshipABSTRACT
Female albino mice were fed sublethal doses of KCN (approx. 10 micrograms/mouse/day) for 7 days, injected intraperitoneally with phenobarbitone (50 mg/kg body wt/day) in the subsequent 3 days, and sacrificed 24 hr after the last injection. Phenobarbitone sleeping time was increasingly shortened (16-27%) daily in cyanide-fed mice in comparison with cyanide-free controls. Both compounds administered singly or simultaneously increased the liver weight/body weight ratios by not more than 10%. Aniline hydroxylase, glucose-6-phosphatase, NADPH- and NADH-cytochrome c reductase activities were similarly increased. Aniline hydroxylase activity was most markedly increased (by a factor of 4). The toxicological implications of these results are discussed.
Subject(s)
Cyanides/pharmacology , Liver/drug effects , Phenobarbital/pharmacology , Potassium Cyanide/pharmacology , Aniline Hydroxylase/metabolism , Animals , Chemical and Drug Induced Liver Injury , Drug Interactions , Female , Glucose-6-Phosphatase/metabolism , Liver/enzymology , Mice , NADPH-Ferrihemoprotein Reductase/metabolism , Phenobarbital/administration & dosage , Phenobarbital/toxicity , Potassium Cyanide/administration & dosage , Potassium Cyanide/toxicityABSTRACT
Aniline hydroxylase, glucose-6-phosphatase, NADPH- and NADH-cytochrome C reductase activities were measured in liver microsomes prepared from four groups of female mice. Mice were fed either control diets alone or KCN (0.357, microgram/kg body wt/day) supplemented diets or control diets plus AFB1 (0.35 microgram/kg body wt/day) administration (ip) on the 8, 9 and 10th day or the KCN supplemented diet plus AFB, administration (ip) on the 8, 9 and 10th day. KCN and AFB1 consistently elevated the activities of the enzymes. Simultaneous administration of both toxins potentiated their effects on the enzymes with the exception of glucose-6-phosphatase. Increases in microsomal protein/liver wt ratios, liver wt/body wt ratios and these enzyme activities were probably indicative of microsomal enzyme induction.
Subject(s)
Aflatoxins/toxicity , Cyanides/toxicity , Microsomes, Liver/enzymology , Mixed Function Oxygenases/antagonists & inhibitors , Aflatoxin B1 , Animals , Body Weight/drug effects , Diet , Female , Liver/drug effects , Mice , Organ Size/drug effects , Rats , Rats, Inbred StrainsABSTRACT
The antimalarial herb, Azadirachta indica, acts by redox perturbation in the form of the imposition of substantial oxidant stress during malarial infection. The aqueous leaf extract substantially inhibited NADPH cytochrome C(P-450) reductase activity in rats with a significant increase in the microsomal protein. The aniline hydroxylase activity and the phenobarbitone metabolism were also enhanced. The flavonoids quercetin-3-rhamnoside and quercetin-3-rutinoside (rutin) were isolated as the major constituents of the extract. The significance of these findings in clinical malaria chemotherapy is discussed.