Action Of Griseofulvin Research Articles

New Meroterpenoids and Anti-Osteoclastogenic Polyketides from the Mangrove-Derived fungus Arthrinium sp. SCSIO 41306.

Two new meroterpenoids, arthrinones A and B (1 and 2), along with six known compounds (3-8), were obtained from the fungus Arthrinium sp. SCSIO 41306. Comprehensive methods such as chiral-phase HPLC analysis and ECD calculations were applied to determine the absolute configurations. Griseofulvin (5), kojic acid (6), and 1H-indole-3-carboxaldehyde (8) showed inhibition of NF-κB in RAW 264.7 macrophages induced by lipopolysaccharide (LPS) with IC50 values of 22.21, 13.87 and 19.31 μM, respectively. In addition, griseofulvin (5) inhibited receptor activator of NF-κB ligand (RANKL)-induced osteoclast differentiation in a dose-dependent manner without visible evidence of cytotoxicity in bone marrow macrophages (BMMs). This is the first report on the activity of griseofulvin (5) to inhibit osteoclast formation (IC50 10.09±0.21 μM).

Effect of griseofulvin on lipid composition and membrane integrity inMicrosporum gypseum

The effect of griseofulvin on lipid constituents and membrane permeability of Microsporum gypseum has been investigated. Mycelia grown in medium containing griseofulvin (IC50 concentration) possessed a lower content of total lipids, phospholipids and sterols. This inhibitory effect was further supported by decreased incorporation of ( 14 C) acetate in total lipids, total phospholipids and sterols. Decrease in total phospholipids was also reflected to a varying extent in all individual phospholipids. An increase in the unsaturated to saturated fatty acid ratio was observed in mycelia grown in medium containing griseofulvin. Membrane permeability was affected by griseofulvin as shown by increased K + -efflux and greater leakage of intracellular ( 32 P) labelled components from prelabelled cells. Our results suggest that the antifungal activity of griseofulvin is partially due to its secondary effect on lipid constituents of Microsporum gypseum.

The effect of griseofulvin on the heme pathway—II. An exhaustive analysis during short and long-term challenge

1. A clear biphasic response of the enzyme activities as a function of intoxication time due to the topical cutaneous griseofulvin treatment was observed. 2. The initial acute induction of ALA-S activity would be due to depletion of free heme in the regulatory pool caused by cytochrome P 450 destruction. 3. The second induction peak, would be due to less heme formation, secondary to the ferrochelatase inhibition, as expected for the erythropoietic protoporphyria model. 4. The biphasic response of hepatic ALA-D and PBGase activities would be related to ALA-S activity changes and the subsequent augmented available substrates. 5. Endogenous liver porphyrin distribution in cytosolic, mitochondrial and nuclear fractions was investigated. 6. The in vitro biosynthesis of porphyrins confirmed both the biphasic model and the hepatic porphyrins subcellular distribution. 7. Two mechanisms to explain the action of griseofulvin at shorter and longer times of intoxication are proposed.

Anti-inflammatory properties of griseofulvin.

Anti-inflammatory activity of griseofulvin has been investigated in comparison with indomethacin and flufenamic acid. In vitro, griseofulvin has been proved the most effective of these agents in suppressing the contractions of smooth muscle preparations induced by a variety of proposed mediators of inflammation, i.e. histamine, 5-hydroxy-tryptamine, bradykinin and prostaglandin E2. In vivo, griseofulvin was unable to modify dextran oedema but suppressed carrageenin oedema, although its activity was poor when compared to that exhibited by indomethacin and flufenamic acid. When tested in rat pleurisy induced by dextran or homologous serum griseofulvin was able to prevent polymorph migration into the pleural space while mononuclears remained virtually unaffected. In contrast indomethacin and flufenamic acid mainly suppressed mononuclear migration while polymorphs resulted only slightly affected. Similar results have been exhibited by the drugs when tested on mononuclear turnover in pleural cavities from normal rats. Results are discussed in the light of the clinically established ability of griseofulvin to prevent cutaneous inflammatory reactions as well as of its effectiveness in the treatment of several polyarthritic syndromes.

Relation of Lipids to the Action of Streptomycin on Bacillus subtilis and Escherichia coli and Griseofulvin and Fungizone on Aspergillus niger

An attempt was made to reveal the relation between the lipid content and components of B. subtilis and E. coli and the action of streptomycin, and those of A. niger and the action of griseofulvin and fungizone (Amphotericin B). Total lipids were extracted in CO2 atmosphere, dried, and weighed. Lipid components were analyzed by thin-layer chromatography. Complements to the growth medium of A. niger with extracted total lipids and phospholipids were made to verify the obtained results. It has been found that the action of streptomycin and griseofulvin was not correlated with lipids. On the other hand, fungizone action was manifested by the decrease in total lipids, free sterols, sterol esters, and triglycerides. Supplementation studies gave evidence of the role of total lipids and phospholipids in protecting A. niger cells against fungizone. Supplementation of 1 g of phospholipid per litre medium raised the M.I.D. of fungizone from 2.5 up to 25 microgram/ml. It was suggested to keep the fat level controlled at a minimum if it is required to increase fungizone activity.

On the mechanism of action of griseofulvin in dermatophytosis.

Guinea pig hair absorbed or adsorbed with griseofulvin was less efficiently hydrolyzed by the extracellular and cell-bound keratinases of Trichophyton mentagrophytes than untreated control hair. The same observations were made using hair from guinea pigs treated orally with griseofulvin. This antibiotic and 3 related compounds had no effect on the active sites of the keratinases. The results of these studies support the hypothesis that resistance to dermatophytic attack is the result of griseofulvin incorporation into keratinous structures causing substrate modification.

The mechanism of action of griseofulvin.

Griseofulvin had no effect on the respiration of Botrytis cinerea but, nevertheless, inhibited growth and caused abnormal hyphal formations, including stunting, spiraling, thickening of the cell wall, and disorientation of growth. Treated cells had an increase in total deoxyribonucleic acid and phosphorus but not in protein, carbohydrate, lipid, and ribonucleic acid. Griseofulvin-treated cells synthesized DNA from labelled glucose and glycine continuously and for much longer periods than control cells so that their total DNA content was greater than that in untreated cells. However, the antibiotic allowed slightly less incorporation with aspartic acid -U-14C as the precursor than the controls. Griseofulvin caused 25 to 50% increased incorporation of carbon into RNA from glucose and glycine but the increases were not due to a prolongation of the synthetic period, and again aspartic acid incorporation was slightly decreased. Griseofulvin was bound to the particulate parts of the cell and was especially high in the lipid fraction of the cell. The antibiotic was not bound to DNA or to RNA.

Anomalous development of the cuticle of mosquitoes induced by griseofulvin.

Griseofulvin is an antibiotic that purportedly interferes with the biosynthesis of cell-walls of fungi which contain chitin. The rearing of larvae of Aedes atropalpus , Coquillett in a medium containing griscofulvin resulted in (a) the occurrence of gross anatomical changes in the cuticle, (b) the detachment of somatic muscles from the integument, and (c) a prolongation of the molting cycle. With the exception of the last-mentioned effect, all modifications became apparent during an instar subsequent to the one initially exposed to the compound. The detachment of muscles from the integument apparently is caused by the anomalous development of the cuticle and not that of the muscles. The effect of griseofulvin on the development of A. alropalpus was shown to be related directly to the molting cycle. The critical period for inducing given anomalies during a molting cycle was determined. The mode of action of griseofulvin is unique in comparison to those of conventional insecticides.

Griseofulvin in the treatment of some deep mycoses.

Soon after the first reports on griseofulvin therapy of skin mycoses we began to use this new drug in Mexico. Our results on dermatophytoses 23 are similar to those of other investigators and they are not the subject of this paper. The action of griseofulvin on deep mycoses was not or scarcely considered in the early studies, because in in vitro observations, Sporotrichum schenckii and other fungi were found insensitive. 3 As deep mycoses are frequent in Mexico we decided, however, to study their response to this therapy. This paper is a preliminary report on this matter. Griseofulvin, as it is well known, was first isolated by Oxford, Raistrick, and Simonart 25 in 1939 as a metabolic product from Penicillium griseofulvum. In 1946, Brian et al. 6 described a fungistatic curlingfactor obtained from Penicillium janczewskii, and its identity with griseofulvin was established by Grove and McGowan 13 the following year.

Thein vitroactivity of griseofulvin on some dermatophytes of veterinary interest

The<i>in vitro</i>activity of griseofulvin on some dermatophytes of veterinary interest