70 research outputs found
Role of Natural Antioxidants in the Modulation of Plasma Amino Acid Pattern in Rats Exposed to Hemic Hypoxia
: Reproductive, cytological and biochemical toxicity of Yohimbe in male Swiss albino mice
Aim: To study the effect of Corynanthe Yohimbe (Yohimbe) on germ cells in Swiss albino mice. Methods: Adult male mice were orally (gavage) treated with different doses (188, 375 and 750 mg/[kg.day]) of aqueous suspension of Yohimbe for 90 days. The following parameters were evaluated: (i) reproductive organ weight, (ii) motility and count of sperm, (iii) study on rate of pregnancy and mean implants, (iv) spermatozoa morphology, (v) cytology of the testes chromosomes, and (vi) biochemical study on estimation of proteins, RNA, DNA, malondialdehyde, nonprotein sulfhydryl (NP-SH) and hormones. Results: The treatment caused significant increase in the weight of seminal vesicles, motility and count of spermatozoa, pre- and post-implants. Male fertility was decreased. These results are confirmed by our data on spermatozoa abnormalities and chromosomal aberrations. The data on biochemical parameters showed increase of malondialdehyde and depletion of NP-SH, proteins, RNA and DNA in the testicular cells. Conclusion: Our results elucidated the role of free radical species in cytological and reproductive changes, possibly, under the influence of yohimbine (principal constituent of Yohimbe) on neurotransmitters, including norephinephrine. These data warrant careful use of Yohimbe
Bioequivalence evaluation of 320 mg gemifloxacin tablets in healthy volunteers.
This study was done to compare the bioavailability of a new tablet formulation of gemifloxacin (gemifloxacin 320 mg/tablet) with that of the reference product (factive 320 mg/tablet). The bioequivalence of a single dose (320 mg) was assessed for gemifloxacin included in the test and reference products by comparing the pharmacokinetic parameters derived from the plasma concentration-time profiles following administration to 24 healthy male volunteers in a balanced, 2-period, 2-sequence, 2-way crossover design. Plasma concentrations of gemifloxacin were analyzed by a validated and sensitive HPLC assay developed in-house. The mean plasma concentration-time profiles are almost superimposable. 18 ANOVAs were performed to compare gemifloxacin plasma levels of the two formulations at each sampling time and there were no statistical differences between the two formulations. The parameters used to measure bioavailability were AUC0-t, AUC0-infinity and Cmax and they were calculated by a model-independent method. The parametric 90% confidence intervals of the mean values for the test/reference ratio were in each case well within the bioequivalence acceptable boundaries of 80-125% for AUCo-t, AUC0-infinity and Cmax. Data obtained in this study prove, by appropriate statistical methods, the essential similarity of plasma levels of gemifloxacin from the test product with those from the reference product suggesting equal clinical efficacy of these two products
Mitodepressive, clastogenic and biochemical effects of (+)-usnic acid in mice.
Mice were treated orally with aqueous suspensions of (+)-usnic acid in a single dose of either 100 or 200 mg/kg. The effects on femur cells and proteins and on nucleic acids of liver cells were studied 24-72 h after treatment. (+)-Usnic acid was found to affect the proliferation of polychromatic erythrocytes possibly by interference with RNA biosynthesis. The slight increase in the micronucleated polychromatic erythrocytes without affecting DNA synthesis suggests an effect of usnic acid on spindle apparatus
The ocular effects of spitting cobras: II. Evidence that cardiotoxins are responsible for the corneal opacification syndrome.
Fractionation of H. haemachatus, N. nigricollis, N. nivea and N. melanoleuca venoms using Amberlite CG-50 and (NH4)HCO3 elution gradient chromatography yielded 11-13 fractions for each venom. One fraction, F X, from H. haemachatus, two fractions, F X and F XI, from N. nigricollis and one fraction, F VIII, from N. melanoleuca venoms possessed the whole of ocular activity of the venoms. The fractions were the only venom fractions that caused cardiac depressant activity; their effect was reversed by raising Ca++ concentration in the physiological solution; they did not influence the twitches of the phrenic nerve hemidiaphragm and guinea-pig ileum preparations. Further purification of the fractions on Sephadex G-50 followed by fractionation on Amberlite CG-50 yielded fractions free from phospholipase A2 activity but possessing the same ocular effects. Similarly, the cardiotoxin from commercial N. nigricollis venom caused the same ocular effects as the crude venom and its purified cardiotoxic fractions. All cardiotoxic fractions as well as N. nigricollis cardiotoxin, caused extensive chemosis, blepharitis and corneal opacification with corneal and subconjunctival neovascularization. On a weight basis, the cardiotoxins were weaker in their oculotoxic activity than the corresponding parent crude venoms possibly because of the potentiating effect of phospholipase A2 in the crude venoms. It is postulated that in spitting cobras the cardiotoxins are responsible for the corneal opacification syndrome. In other cobra venoms the stable binding of cardiotoxins with acidic proteins limits their possible ocular effects. Only in the venoms of the spitting species are the cardiotoxins present in an appropriately free form to cause the ocular opacification syndrome
Effect of (+/-)-verapamil and hydralazine on stress- and chemically-induced gastric ulcers in rats.
The influence of (+/-)-verapamil and hydralazine on stress- and various chemically-induced gastric ulcers in rats together with their influence on various biochemical parameters which affect the development of the induced ulcers was examined. Pretreatment of rats with (+/-)-verapamil (4-16 mg kg-1 orally) significantly decreased cold-stress-induced gastric ulcers and enhanced ethanol-induced ulcers. It did not affect indomethacin- (30 mg kg-1 orally) or reserpine- (5 mg kg-1 i.p.) induced ulcers. Pretreatment of the animals with hydralazine (1-10 mg kg-1 orally) significantly enhanced ethanol-, reserpine- and cold-stress-induced ulcers. It did not affect indomethacin-induced ulcers. Pretreatment of the animals with verapamil increased gastric mucus secretion, inhibited gastric acid secretion, decreased glutathione content and enhanced gastric lipid peroxidation whereas pretreatment of the animals with hydralazine significantly decreased gastric mucus secretion. Hydralazine did not affect gastric acid secretion, glutathione or gastric lipid peroxidation. The results of this study suggest that verapamil-induced protection against stress-induced ulcer may be due to its ability to suppress gastric acid secretion and to increase gastric mucus secretion. Its enhancement of ethanol-induced ulcers may be due to its ability to increase lipid peroxidation. The hydralazine-induced enhancement of the experimentally-induced ulcers may be due to its ability to suppress gastric mucus secretion
Evidence for superoxide radical production by a simple flavoprotein: glucose oxidase
Nitroblue tetrazolium was reduced to blue formazan during the oxidation of glucose by glucose oxidase. The rate of blue color formation was dependent on the concentrations of glucose, nitroblue tetrazolium and glucose oxidase. The rate of the reaction was negligible below pH 8.4, but sharply increased with increasing pH. The reduction of nitroblue tetrazolium was inhibited by superoxide dismutase, consistent with the participation of superoxide anion radical in the reaction
Effect of ninhydrin on the biochemical and histopathological changes induced by ethanol in gastric mucosa of rats.
Studies on the effect of ninhydrin in the normal gastric mucosa and against the ethanol induced gastric injury were undertaken in rats in view of the presence of a carbonyl function as well as hydroxyl groups in its chemical structure. In spite of its potentials to generate hydroxyl radicals, it is deemed to possess antioxidant property by virtue of its electrophilic nature. Recent studies have shown gastro-protection to mediate through a reaction between the electrophilic compounds and sulfhydryl groups of the mucosa. Hence it was found worthwhile to evaluate the interaction between the oxidant and antioxidant functions in the structure of the same compound. The effects of ninhydrin pretreatment on gastric mucosal injuries caused by 80% ethanol, 25% NaCl and 0.2M NaOH were investigated in rats. The gastric tissue in ethanol-treated rats was analyzed for different histopathological lesions. In addition, the effects on ethanol-induced changes in the gastric levels of proteins, nucleic acids, non-protein sulfhydryl (NP-SH) and malondialdehyde (MDA) were also evaluated. Ninhydrin, as such, failed to induce any significant changes in normal gastric mucosa, while its pretreatment at oral doses of 5, 10 and 20 mg/kg was found to provide a dose-dependent protection against the ulcers induced by ethanol, NaOH and NaCl. The results of histopathological evaluation revealed a protective effect of ninhydrin on congestion, hemorrhage, edema, erosions and necrosis caused by ethanol. Furthermore, the pretreatment afforded a dose-dependent inhibition of the ethanol-induced depletion of proteins, nucleic acids, NP-SH and increase of MDA in the gastric tissue. The results obtained clearly demonstrate the anti-ulcerogenic activity of ninhydrin. The exact mechanism of action is not known. However, the carbonyl function in ninhydrin appears to achieve antioxidant balance and protect the gastric mucosa from the ethanol-induced gastric injury. Further studies are warranted to investigate the toxicity and detailed mechanism of action of this potent compound before any clinical trials, especially at the effective lower doses
: Mitodepressive, clastogenic and biochemical effects of (+)-usnic acid in mice.
Mice were treated orally with aqueous suspensions of (+)-usnic acid in a single dose of either 100 or 200 mg/kg. The effects on femur cells and proteins and on nucleic acids of liver cells were studied 24-72 h after treatment. (+)-Usnic acid was found to affect the proliferation of polychromatic erythrocytes possibly by interference with RNA biosynthesis. The slight increase in the micronucleated polychromatic erythrocytes without affecting DNA synthesis suggests an effect of usnic acid on spindle apparatus
Pathomorphological oranges in mouse liver and kidney during prolonged valproate administration
Mice given sodium valproate 0.71% weight/volume in drinking water for 7, 14 and 21 days were assessed for pathomorphological changes in liver and kidney tissues at certain time points. This treatment caused a marked alteration in liver and kidney cell morphology which was proportional to the period of treatment. This treatment induced fatty degeneration of hepatocytes, increased the number of Kupffer cells and caused them to swell. These changes were irregular after days 7 and 14 of treatment but with time increased in intensity, producing inflammation of the portal tracts, albuminous degeneration and necrosis of septa. Precirrhotic conditions, cirrhosis, acidophilic degeneration of hepatocytes and glassy eosinophilic homogenous cytoplasm were a constant feature after 21 days' treatment. In some cases the portal area was invaded by small, round inflammatory cells. Hepatocytes in this group were swollen, with large nuclei and increased amounts of condensed chromatin. The kidney sections of the same animals revealed severe morphological changes, indicated by significant epithelial necrosis and sloughing of tubules, as well as cast formation and mild lymphocytic infiltrate after 21 days' treatment. The results suggest that the histopathologic changes induced by sodium valproate are dependent upon the duration of exposure of these organs to the drug. Prolonged use of this drug should be carefully assessed
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