Toxicology of Azadirachta indica.
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Animals↗
Biomedical subjects
B H Ali
Publications and source records attributed to B H Ali.
Effect of fish oil treatment on gentamicin nephrotoxicity in rats.
The effect of fish oil on gentamicin-induced nephrotoxicity was investigated in rats. Gentamicin (80 mg/kg/day intramuscularly for 6 days) produced the typical pattern of nephrotoxicity as shown by increases in serum creatinine and urea concentrations, and urinary N-acetyl-beta-D-glucosaminidase (NAG) activity and proximal renal tubular necrosis. Fish oil (5.0 ml/kg/kday per os for 10 days) partially protected against the nephrotoxicity induced by gentamicin administered during the last 6 days of treatment with fish oil by returning the creatinine and urea concentrations and NAG activity to normal and by ameliorating the histopathological damage. Olive oil (5 mg/kg/day per os for 10 days) was ineffective in protecting rats against gentamicin nephrotoxicity.
Acetylglucosaminidase↗
Comparative modulating effects of captopril, diltiazem, dietary calcium and pyridoxal-5'-phosphate on gentamicin-induced nephrotoxicity in the rat.
1. Nephrotoxicity was induced in rats by injecting gentamicin intramuscularly (i.m.) at a dose of 80 mg/kg/day for 6 days. Treated animals demonstrated a typical pattern of aminoglycoside nephrotoxicity characterized histopathologically by necrosis of proximal tubular epithelium, and biochemically by increased serum creatinine and urea concentrations. Reduced glutathione (GSH) concentration in renal cortex was significantly decreased by gentamicin. 2. Simultaneous treatment of rats with gentamicin and either captopril or diltiazem significantly potentiated the gentamicin-induced increases in serum creatinine and urea and did not significantly affect the gentamicin-induced decrease in cortical GSH concentration. 3. Concomitant treatment with gentamicin and either Ca2+ or pyridoxal-5'-phosphate decreased serum urea level, did not significantly affect serum creatinine concentration, and significantly increased cortical GSH concentration in comparison to the values of these parameters following gentamicin treatment. 4. Histopathologically, the severity of gentamicin-induced renal damage was exacerbated by captopril, and even more so by diltiazem. Simultaneous treatment with gentamicin and either Ca2+ or pyridoxal-5'-phosphate produced only mild focal atrophy of renal tubular epithelium. Control rats had apparently normal histology. 5. In conclusion, captopril and diltiazem, at the doses used, significantly potentiated gentamicin-induced nephrotoxicity to a broadly similar extent. Although Ca2+ and pyridoxal-5'-phosphate, at the doses used, reduced significantly the severity of some of the manifestations of nephrotoxicity, they were equally ineffective in completely preventing the development of nephrotoxicity.
Animals↗
The effect of some alpha 2-adrenoceptor agonists and antagonists on gastrointestinal transit in mice: influence of morphine, castor oil and glucose.
1. The effects of graded doses of the alpha 2-adrenoceptor agonists clonidine, tizanidine and BHT-920, and the alpha 2-adrenoceptor antagonists yohimbine and idazoxan, on gastrointestinal transit were investigated in mice using the charcoal meal test. 2. The agonists produced significant and dose-dependent decreases in gastrointestinal transit, and the antagonists produced the opposite effect. In affecting the gastrointestinal transit, clonidine (1 mg/kg) was as effective as tizanidine (12 mg/kg) and BHT-920 (40 mg/kg), while yohimbine (2 mg/kg) was as effective as idazoxan (1 mg/kg). 3. Morphine (2, 4 and 8 mg/kg) significantly inhibited gastrointestinal transit. This effect was significantly reversed by the co-administration of yohimbine (2 mg/kg) and idazoxan (1 mg/kg). 4. The acute administration of glucose (5.04 g/kg, i.p.) potentiated the inhibition of gastrointestinal transit produced by clonidine (1 mg/kg) and BHT-920 (40 mg/kg). Glucose treatment, however, had no significant effect on the increase in gastrointestinal transit induced by yohimbine (2 mg/kg) or idazoxan (1 mg/kg). 5. Castor oil (0.25 mL/mouse, orally) induced diarrhoea in saline-treated animals within about 45 min. Clonidine (1 mg/kg), tizanidine (12 mg/kg) and BHT-920 (40 mg/kg) delayed the occurrence of diarrhoea to 2.1, 1.2 and 1.4 h, respectively.
Adrenergic alpha-Agonists↗
Comparative study of salivary acetaminophen concentration in Libyans, Senegalese and Sudanese.
In the first of two experiments, acetaminophen (paracetamol) was measured in the saliva of healthy male and female Sudanese, Libyan and Senegalese volunteers. Saliva was collected 1 h after ingesting 1 g of the drug. In the second experiment, acetaminophen (1 g) was given orally to male Sudanese and Libyan volunteers, and saliva was collected 0.5, 1, 2, 3, 4, 5 and 6 h thereafter. The drug concentration in both experiments was measured by a modified spectrophotometric method with a detection limit of 1 microgram/ml. The results indicated that the salivary acetaminophen concentration in Sudanese was significantly (p < 0.05) higher in males than females by about 28%. In Libyans, the drug concentration in males was 19% higher than in females (insignificant, p > 0.05). There were no statistically significant differences in salivary acetaminophen concentrations between Sudanese, Libyans and Senegalese volunteers, although male Senegalese had higher levels than the Sudanese and Libyans by 11.4 and 15.8%, respectively. Acetaminophen salivary concentrations in Sudanese were slightly but significantly (p < 0.05) higher than those in Libyans 0.5 and 1.0 h after ingestion of the drug. Thereafter, there were no significant differences in the drug concentrations between the two groups (p > 0.1). The results of both experiments do not support the suggestion of inter-ethnic differences in acetaminophen clearance, but indicate that males may clear more of the drug through saliva than females.
Acetaminophen↗
Serum angiotensin-converting enzyme activity in rats with gentamicin-induced nephrotoxicity.
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Animals↗
Plasma lipid profile in rats with gentamicin-induced nephrotoxicity.
1. Administration of gentamicin to rats at doses of 20, 40 or 80 mg kg-1 d-1 for 6 days induced nephrotoxicity exhibited by elevated plasma creatinine concentration and a decrease in alkaline phosphatase activity in rat kidney cortex. 2. Gentamicin treatment produced significant elevation in plasma total cholesterol amounting to 70% at the 80 mg kg-1 dose. At this dose, the combined cholesterol fractions of low density and very low density lipoproteins increased by more than two-fold. 3. Gentamicin treatment also caused significant increase in plasma triglyceride concentration, while plasma phospholipid levels showed dose-dependent reductions. 4. In another experiment recovery of the aforementioned parameters was assessed 7 and 14 days after the withdrawal of gentamicin, administered at a dose of 40 mg kg-1 d-1 for 6 days. After 7 days from drug discontinuation, both plasma creatinine and total cholesterol concentrations returned to the control levels, while triglyceride concentration was still significantly higher than control 14 days after stoppage of treatment. 5. Plasma phospholipid concentration and the activity of cortical alkaline phosphatase were still significantly lower than control 14 days after cessation of the treatment.
Alkaline Phosphatase↗
Some comparative aspects of drug metabolism in nubian goats (Capra hircus), desert sheep (Ovis aries) and dromedary camels (Camelus dromedarius).
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Animals↗
Effect of furazolidone on tissue sulphydryl groups, ascorbic acid, and lipid peroxide levels in the rat, and the influence of dimethylsulphoxide thereon.
The concentrations of sulphydryl groups (SH), ascorbic acid (AA) and lipid peroxide (LP) were measured in the liver, kidney and brain of rats 24 h after treatment with furazolidone at single oral doses of 75, 150 and 300 mg/kg. The drug produced significant reductions in the concentrations of SH, and significant increases in the concentrations of LP, in the tissues studied. The level of AA was significantly decreased in the livers (but not the kidneys or brains) of rats treated with furazolidone at a dose of 300 mg/kg. The concentrations of AA in the tissues of rats treated with lower doses were unaffected. In another experiment, furazolidone was given orally to rats at a dose of 300 mg/kg, together with a subcutaneous injection of dimethylsulphoxide (DMSO) at a dose of 8 g/kg, and SH measured in the liver 24 h later. DMSO alone had no significant effect on SH concentration. However, when DMSO was given concomitantly with furazolidone, SH concentration was significantly less depressed than when furazolidone was given alone. It is concluded that DMSO protected tissues against toxicity induced by furazolidone.
Analysis of Variance↗
Gentamicin nephrotoxicity in rat: some biochemical correlates.
The present work examines the effect of treatment of rats with graded doses of the aminoglycoside antibiotic gentamicin on the concentration of reduced glutathione (GSH) and diamine oxidase (DAO) activity in the kidney, and DAO activity, creatinine and magnesium (Mg) in the plasma. The animals were given the antibiotic intramuscularly in doses of 20, 40, and 80 mg/kg/day for 6 days, and were killed 24 hr after the last injection. In another experiment rats were injected intramuscularly with gentamicin at a dose of 80 mg/kg/day for 6 days and were killed 1, 7 or 14 days after the last injection, and the above parameters were measured. Gentamicin reduced the body weights of rats in a dose-dependent manner. The weight reductions were most marked on days 4, 5 and 6 of the treatment. The body weights gradually recovered on withdrawing of the drug, and by day 14, they were not significantly different from those of the controls. Gentamicin produced significant and dose-dependent decreases in the renal concentration of GSH. Seven and 14 days after withdrawing the drug, the GSH concentrations were still significantly below that of the controls. Plasma Mg concentrations were significantly decreased, and plasma creatinine concentrations significantly increased by gentamicin. These effects persisted 7 and 14 days after cessation of treatment. Plasma DAO activity was not detectable in the control or gentamicin-treated rats. In the renal cortex, the activity of the enzyme, measured 1, 7 and 14 days after the treatment, was not significantly different from that of the control. Histopathologically, the drug produced dose-dependent proximal renal tubular necrosis.(ABSTRACT TRUNCATED AT 250 WORDS)
Amine Oxidase (Copper-Containing)↗
Diamine oxidase activity in the duodenal mucosa of rats with cysteamine-induced ulceration.
Cysteamine administration to rats is followed by a high incidence of duodenal ulceration. The effect of cysteamine on the activity of diamine oxidase (DAO, histaminase) in the duodenal mucosa of the rat was investigated. Rats were injected subcutaneously with cysteamine on 2 successive days at doses of 10, 20 and 40 mg/100 g body weight and killed 24 h after the second dose. The results indicated that cysteamine at a dose of 40 mg/100 g body weight inhibited enzyme activity by about 27% (p less than 0.05). Lower doses of cysteamine did not significantly affect enzyme activity. In another experiment, rats were injected subcutaneously with either saline (control) or cysteamine at a single dose of 40 mg/100 g body weight and killed 4, 8, 12, 24, 48 and 60 h thereafter. The ulcerogen produced progressive reductions in enzyme activity, which were significant at 12 h (22% reduction) and 24 h (25% reduction). At 60 h, enzyme activity was not significantly different from that of control.
Amine Oxidase (Copper-Containing)↗
Lipid peroxidation, glutathione and ascorbic acid concentrations in tissues of mice treated with oltipraz: influence of cysteine and olive oil pretreatments.
1. The effects of treatment with the antischistosomal drug oltipraz on reduced glutathione (GSH), lipid peroxide (LP) and ascorbic acid (AA) concentrations in the liver, kidney and brain were studied in mice 24 h after drug administration. 2. The influence of pretreatment with cysteine or olive oil on the above variables in oltipraz-treated mice was also investigated. 3. Oltipraz, at single oral doses of 25 and 125 mg/kg, did not affect significantly the concentrations of GSH, LP or AA in any of the tissues studied. 4. At a dose of 625 mg/kg, the drug produced significant increases in GSH concentration in the liver (about 34%), kidney (38%) and brain (24%). 5. AA concentrations were not significantly affected by the drug treatment in any of the organs studied. 6. However lipid peroxide formation in the liver of mice treated with oltipraz (625 mg/kg) was less than that in control animals by about 45% (P less than 0.05). 7. In other organs it was not significantly affected by the treatment. 8. Oltipraz (625 mg/kg) was given orally to mice which were pretreated with cysteine (25, 50 and 100 mg/kg for 7 days intramuscularly). 9. The cysteine pretreatments did not affect significantly the increases in GSH caused by oltipraz alone, although they were effective in significantly increasing GSH concentrations in saline-treated mice. 10. The oltipraz-induced increases in the concentrations of GSH in liver and kidney was enhanced (by about 16%) by olive oil (0.2, 02 and 0.4 ml/mouse) when given 1 h before oltipraz treatment. 11. Concentrations of LP and AA were not significantly affected by olive oil pretreatment.
Animals↗
Activities of glutathione-S-transferase and ethoxycoumarin-O-deethylase in tissues of camels, sheep, goats and rats.
1. The activities of the drug metabolizing enzymes ethoxycoumarin-O-deethylase, glutathione-S-transferase, and protein concentrations were measured in vitro in the liver, kidney and duodenal mucosa of camels, sheep, goats and rats. 2. Enzyme activities were generally higher in the liver than in the kidney and duodenal mucosa in the four species studied. 3. The activities of ethoxycoumarin-O-deethylase and glutathione-S-transferase in liver of male kids were about one third and half of that in adult male goats, respectively. In the kidney and duodenal mucosa of male kids, the activity of glutathione-S-transferase was about 70% and 53% of that in the mature male goat, respectively. In the latter tissues, however, there was no detectable activity of ethoxycoumarin-O-deethylase. 4. In general, goats and sheep had similar activities of the two enzymes which were significantly higher than those found in camels and rats. 5. Some sex-related differences were noted in the activity of the two enzymes studied. Female sheep had significantly higher hepatic glutathione-S-transferase than the male: while the enzyme activity in the kidney and duodenal mucosa of male goats was significantly higher than in females. Male rats had higher hepatic ethoxycoumarin-O-deethylase activity than females.
7-Alkoxycoumarin O-Dealkylase↗
The activities of drug-metabolizing enzymes in goats treated orally with the latex of Calotropis procera and the influence of dieldrin pretreatment.
The effects of oral administration of different doses of the latex of Calotropis procera on the activities of drug-metabolizing enzymes in the liver, kidneys and duodenal mucosa of Nubian goats were investigated. Lesions and changes in total plasma protein concentration and in the activities of plasma sorbitol dehydrogenase (SD), glutamate dehydrogenase (GD) and aspartate aminotransferase (AST) were studied. The daily oral administration of the latex at dose rates of 0.4 and 0.8 ml per kg for 7 days resulted in a significant inhibition of the activity of aniline 4-hydroxylase. No signfiicant effects on the activities of aminopyrine N-demethylase and UDP-glucuronyltransferase were observed. A single oral dose of 1.2 or 1.6 ml per kg killed goats within 7 h and resulted in increased activities of aminopyrine N-demethylase and aniline 4-hydroxylase. UDP-glucuronyltransferase was found to be insensitive to tissue injury induced by the latex of C. procera. There were no pathological changes in goats given 10 mg per kg of dieldrin alone or in those pretreated with dieldrin and given the latex at a dose rate of 1.2 ml per kg 14 days later. Dieldrin pretreatment resulted in the induction of the activities of drug-metabolizing enzymes in the liver, kidneys and duodenal mucosa and it may have protected goats from the lethal effects of the latex.
Administration, Oral↗
Pharmacokinetics of antipyrine and sulphadimidine (sulfamethazine) in camels, sheep and goats.
The pharmacokinetics of antipyrine and sulphadimidine were studied in male camels, sheep and goats. The two drugs were administered concomitantly. Following intravenous injection of antipyrine (25 mg/kg) and sulphadimidine (sulfamethazine) (100 mg/kg), the pharmacokinetics of the two drugs were adequately described by a one-compartment model. Antipyrine half-life in goats (2.58 h) was shorter than that in sheep (4.04 h) and camels (18.78 h). The plasma clearance was greatest in goats then sheep and then camels. For sulphadimidine, a significantly greater volume of distribution was observed in camels and the greatest plasma clearance and shortest half-life were reported in goats. Sulphadimidine half-life was 2.77 h in goats, 4.72 h in sheep and 7.36 h in camels. The present results suggest that goats have the fastest elimination of these drugs from the circulation, followed by sheep and then camels.
Animals↗
Effect of nitrofurans on duodenal ulceration induced by cysteamine or indometacin.
The present experiments examined the protective effect of the nitrofuran drugs, furazolidone (FZ) and nitrofurazone (NF), on duodenal ulceration induced by cysteamine or indometacin in rats. FZ at oral doses of 25, 50 or 100 mg/kg for 2 consecutive days signficantly reduced, in a dose-dependent manner, the incidence and extent of cysteamine-induced ulceration. However, oral NF (100 mg/kg) given for 2 consecutive days had no significant effect on duodenal ulceration. The duodenal mucus content of rats was not significantly affected by either FZ or cysteamine treatments. FZ at an oral dose of 100 mg/kg for 2 consecutive days significantly reduced the incidence and extent of indometacin-induced ulceration. Smaller doses of 25 or 50 mg/kg had no significant effects.
Animals↗
Pharmacokinetics of niclofolan in desert sheep.
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Administration, Oral↗
The effect of ivermectin on some haematological indices in rabbits: influence of vitamin K treatment.
1. Rabbits were treated with the antiparasitic drug ivermectin at subcutaneous doses of 0.2, 1 and 2.5 mg/kg and blood collected weekly for 4 weeks thereafter for measuring some blood parameters. At a dose of 0.2 or 1 mg/kg the drug had no significant effect on any of the parameters measured. At a dose of 2.5 mg/kg, the drug reduced significantly the erythrocyte counts, haemoglobin concentration, haematocrit, mean corpuscular haemoglobin concentration and mean corpuscular haemoglobin on weeks 1, 2, 3 and 4. Platelet counts were not significantly affected. 2. In another trial, ivermectin was injected subcutaneously at a dose of 2.5 mg/kg, after pre-treatment with either saline or vitamin K (30 micrograms/kg for 30 days), and prothrombin time, bleeding time and platelet counts measured at weekly intervals for 4 weeks. Bleeding time and thrombin time were significantly increased 1 week after treatment, and remained higher than the control for 4 weeks.
Animals↗