The secondary dyslipidemia and deranged serum phosphate concentration in thyroid disorders.

Hyperlipidemia is a secondary disorder associated with many metabolic disorders including hypothyroidism. The occurrence of dyslipidemia in subclinical hypothyroidism is controversial. Hyperphosphatemia may accompany the dyslipidemia in some metabolic disorders. Both hyperlipidemia and hyperphosphatemia are considered to be risk factors for the coronary heart diseases. In the present study, we investigated the occurrence of dyslipidemia and altered serum phosphate concentrations in patients with thyroid disorders. The results indicated a significantly elevated serum cholesterol and triglyceride concentrations in the hypothyroid patients. The dyslipidemia was accompanied with significantly elevated serum phosphate level. On the other hand, no significant difference was evident in the serum lipid or phosphate concentrations of subclinical hypothyroid patients compared to euthyroid subjects. A significantly reduced serum phosphate level was shown in hyperthyroid patients with unaltered serum lipid levels. Significant correlations were evident between TSH and T(4) levels as independent parameters and the serum concentrations of triglyceride, cholesterol and phosphate. The results indicate in hypothyroidism that a secondary hyperphosphatemia may aggravate myocardial and arterial abnormalities induced by the secondary hyperlipidemia, which may need correction.

Effect of high dietary cholesterol on gentamicin-induced nephrotoxicity in rabbits.

Administration of gentamicin to rabbits intramuscularly at a dose of 80 mg/kg per day for 5 days induced nephrotoxicity exhibited by significantly (P < 0.001) elevated serum urea and creatinine levels and a significant (P < 0.001) decrease in renal cortical alkaline phosphatase (ALP) activity, in addition to tubular necrosis revealed by the histopathological examination of the kidney cortices. The deranged parameters returned to normal within 1 week of drug withdrawal, except the cortical ALP activity, which was still significantly lower compared to control. In contrast, feeding of 2% cholesterol-supplemented diet (CSD) to the rabbits for 15 days did not produce any nephrotoxic effects. However, the concurrent feeding of CSD for 15 days and gentamicin treatment at a dose of 80 mg/kg per day for 5 days, starting from day 10 of feeding, resulted in extensive nephrotoxic effects which were more severe than those observed with the gentamicin alone, with delayed recovery of the injured kidney following drug withdrawal. Gentamicin treatment produced significant elevation in serum total cholesterol, which was greater in animals fed with CSD. The serum triglyceride levels in the groups injected with gentamicin were also significantly greater than their respective controls. However, the serum phosphlipids were significantly reduced with gentamicin treatment and this reduction was greater in animals fed with cholesterol and treated with the drug. The liver cholesterol contents in animals fed with the CSD were significantly higher than those fed with the plain diet. However, the kidney cortices of the animals injected with the gentamicin showed significantly increased total phospholipid contents compared to their respective controls. On the other hand, the liver function was not altered in any of the experimental groups. In summary, the present results suggest that cholesterol feeding exacerbated the gentamicin-induced nephrotoxicity. Moreover, it delayed the period required by the injured kidney to recover back to normal. However, neither gentamicin treatment nor cholesterol feeding, or both together, had any injurious effects on the liver.

Effect of spironolactone on cisplatin-induced nephrotoxicity in rabbits.

The effects of a single interaperitoneal dose of cisplatin (6.5 mg kg day(-1)), oral doses of spironolactone (20.0 mg kg day(-1)) for 5 days or the combined treatment (spironolactone+cisplatin) on the kidney function and liver function parameters, as well as the serum, liver and kidney cortical lipid contents were studied. The serum urea and creatinine concentrations (measured as kidney function parameters) were not altered by spironolactone treatment, but were significantly (P<0.001) elevated by cisplatin administration. However, animals exposed to both spironolactone+cisplatin revealed drastic increases in the serum creatinine and urea concentrations amounting to about four- and twofold those of cisplatin-alone treated animals, respectively. The histological examination of slides of kidneys from animals exposed to the combined drugs exhibited more extensive necrosis in the tubules compared to those from animals treated with cisplatin alone. Non of the drug treatments had any effects on the serum alanine transaminase (ALT) and aspartate transaminase (AST) levels (measured as liver function parameters) or liver protein content or hepatic alkaline phosphatase (ALP) activity. The histological examination also revealed apparently normal livers in all experimental groups. The cisplatin-induced nephrotoxicity was accompanied by hypercholesterolaemia and hyperphospholipidaemia, whereas spironolactone showed a hypocholesterolaemic effect. The concomitant treatment with both cisplatin and spironolactone significantly (P<0.05) raised the serum triacylglycerol (TAG) concentration compared to the cisplatin-alone-treated group. Both spironolactone and cisplatin administered separately or jointly caused accumulation of cholesterol and TAG in the kidney cortex with significant depletion of the liver cholesterol content. The present results indicated that spironolactone aggravates the cisplatin-induced nephrotoxicity in the rabbit.

Hyperlipidaemia in cisplatin-induced nephrotic rats.

The serum and hepatic lipid concentrations were investigated in rats made nephrotic with a single intraperitoneal injection of cisplatin (6 mg kg(-1) b.wt.). The serum creatinine and urea concentrations were estimated as indices of nephrotoxicity, and the serum total bilirubin level as a liver function test. 3 The fasting serum total cholesterol, triglycerides (TG) and the cholesterol fractions associated with the various lipoproteins, as well as hepatic cholesterol and TG contents were also measured, following 5, 10 and 15 days from the cisplatin treatment. 4 The results revealed that on day 5 both serum creatinine and urea concentrations were significantly (P<0.01) increased, indicating the peak of nephrotoxicity, with no injurious effects on the liver as indicated by the unaltered serum bilirubin concentration. 5 The nephrotoxicity was accompanied by significant elevations in serum total cholesterol and TG concentrations by 49 and 42%, respectively, with significant (P < 0.05) correlations between the serum cholesterol and TG concentrations versus the serum urea (r=0.68 and r=0.60, respectively). Among the estimated lipoproteins, very low density lipoprotein (VLDL) cholesterol was severely increased to more than twofold with no severe changes in LDL- or HDL-cholesterol fractions. On day 5 the liver also showed significant accumulation of TG with no change in the cholesterol content. Animals killed 10 or 15 days post-cisplatin treatment had all the perturbed parameters returned to the normal levels. The present results indicated that rats exposed to a single cisplatin injection exhibit acute reversible nephrosis on day 5 which was accompanied by dyslipidaemia and accumulated liver TG.

Effect of selenium on vanadium toxicity in different regions of rat brain.

The protective effect of selenium on the neurotoxicity of vanadium in different brain regions of rats was investigated. The lipid peroxidation was significantly accentuated after intraperitoneal (i.p.) administration of vanadium (1.5 mg kg-1 b.wt) for a period of 12 consecutive days to rats. The increase in lipid peroxidation was inhibited by selenium treatment (0.02 mg kg-1 b.wt., i.p.) for 12 consecutive days. Vanadium exposure produced a decrease in nonprotein sulfhydryl group. Selenium treatment prevented the depression in nonprotein sulfhydryl group in all the brain regions of the vanadium exposed rats. The concentration of ascorbic acid was decreased after co-administration of selenium and vanadium. These results suggest that selenium protects neuronal cells against neurotoxic effects of vanadium by maintaining the availability of antioxidant nonprotein sulfhydryl groups. The decrease in ascorbic acid levels may have been due to its consumption in forming complexes with vanadium.

Effects of fish oil and sunflower oil supplementations on gentamicin-induced nephrotoxicity in rat.

1. Nephrotoxicity was induced in rats by intramuscular administration of gentamicin (80 mg k-1 d-1) for 6 days. 2. Oral supplementation with fish oil (5 ml kg-1 d-1), for 2 weeks prior to and during gentamicin exposure, markedly ameliorated the drug-induced nephrotoxicity. The beneficial effects of oil were evidenced by significantly reduced serum creatinine and urea concentrations, increased renal cortical alkaline phosphatase activity and improved renal tubular histology, compared with the non oil-treated animals, receiving gentamicin. 3. Similar supplementation with sunflower oil, rich in omega-6 fatty acids, failed to reverse any of the parameters of nephrotoxicity induced by gentamicin. 4. Hypercholesterolaemia and reduced cortical GSH associated with gentamicin nephrotoxicity were both normalised by supplementation with fish oil, but not by sunflower oil. 5. The beneficial effects of fish oil on gentamicin-induced nephrotoxicity were not related to the extent of uptake and accumulation of the drug by the kidney.

Effect of gentamicin-induced nephrotoxicity on some carbohydrate metabolic pathways in the rat renal cortex.

Rats were injected with gentamicin at doses of 20, 40 and 80 mg/kg per day for 6 consecutive days. The treatment caused nephrotoxicity as evidenced by dose-related increases in serum creatinine concentration and renal tubular necrosis. The nephrotoxicity was accompanied by reduced renal cortical and fasting blood glucose levels, and by increases in serum lactate concentrations. The activities of cortical malate dehydrogenase and alanine transaminase were significantly reduced by the three doses of gentamicin. On the other hand, aspartate transaminase activity was lowered only by the highest dose of antibiotic used. However, the activity of cortical glucose-6-phosphate dehydrogenase was altered by the 20 and 40 mg/kg doses of gentamicin, but not by the 80 mg/kg dose. The two lower doses reduced the lactate content of the cortex but activated lactate dehydrogenase. The activity of isocitrate dehydrogenase was not altered by any of the gentamicin doses used.

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.

Effect of chloroquine on some carbohydrate metabolic pathways: contents of GHS, ascorbate and lipid peroxidation in the rat.

Adult male rats were treated intraperitoneally with chloroquine (5 mg/kg/day) for 9 days. A reduction in the fasting plasma glucose level by 17.6% and ascorbic acid by 45% were discernable. The treatment caused significant increase in liver lactate dehydrogenase and glucose-6-phosphate dehydrogenase activities and reduced the activity of succinate dehydrogenase enzyme. Chloroquine also caused significant reductions in the contents of reduced glutathione and ascorbic acid in the brain and erythrocytes with a significant increase in lipid peroxidation.

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)

Glutathione and ascorbic acid concentrations in the duodenum of rats with cysteamine-induced ulcers: influence of cysteine and ascorbic acid pretreatments.

Duodenal ulceration in rats was induced by a single subcutaneous injection of cysteamine at doses of 7, 28, 42 and 65 mg/100 g body weight 24 h before killing. Duodenal ulceration induced by cysteamine was dose-dependent. However, at 65 mg/100 g body weight, 5 of 6 animals died within 24 h. The concentrations of reduced glutathione (GSH) and ascorbic acid were measured in the duodenal homogenates of cysteamine-treated rats. The ulcerogen, at doses of 28 and 42 mg/100 g body weight, significantly reduced the GSH concentration. At a dose of 28 mg/100 g body weight, however, it did not significantly affect the duodenal ascorbic acid concentration. Pretreatment of rats with daily intramuscular injections of cysteine at 25, 50 and 100 mg/kg or ascorbic acid at 50, 100 and 200 mg/kg for 7 days had no significant effect on the duodenal ulceration produced by cysteamine (28 mg/100 g body weight), although each pretreatment significantly raised the duodenal concentrations of GSH and ascorbic acid respectively, in control rats, and to a lesser extent in cysteamine-treated animals.