Marco Fidaleo

Peroxisomes and peroxisomal disorders: The main facts

The importance of peroxisomes for human health is highlighted by the number of peroxisomal disorders (PDs), diseases associated to peroxisome biogenesis disorders and peroxisomal enzyme/transporter deficiencies. Currently, many physiological/biosynthetic mechanisms involved in these illnesses have been elucidated, but PDs remain incurable. This review examines the most important aspects concerning peroxisomes (i.e. peroxisome proliferation, peroxisome biogenesis, metabolic functions of mammalian peroxisomes) and presents the most significant trends and advances in the study of peroxisomal disorders.

Human health risk assessment for peroxisome proliferators: more than 30 years of research.

Substances like gemfibrozil, clofibrate and fenofibrate, widely used in human care for their hypolipidemic effects, belong to a larger class of chemicals called peroxisome proliferators (PPs). PPs, by binding and activing the peroxisome proliferator-activated receptor alpha (PPARalpha), modulate gene involved in lipid homeostasis both in human and in rodent. In a different way, long term administration of PPs results in hepatocarcinogenesis only in rodent. Although the phenomenon is known since more than 30 years, the exact mechanism is not well understood and the human health risks are not established. In this mini-review is inspected the major findings done in the different species and illustrates the possible doubts for human health by the use of PPs.

Enhanced antibacterial and anti-quorum sensing activities of triclosan by complexation with modified β-cyclodextrins

Triclosan (TCS), an antimicrobial agent widely used in consumer and medical products, was complexed with 2-hydroxypropyl-β-cyclodextrin (HPβCD) and methyl-β-cyclodextrin (MβCD). Phase-solubility studies indicated that inclusion complexes of 1:1 stoichiometry were formed and allowed estimation of the associated equilibrium constants and free-energy changes. At the highest cyclodextrin concentrations investigated, an almost 20-fold increase in the apparent water solubility of TCS was determined. Susceptibility tests against Escherichia coli and Staphylococcus aureus showed that the TCS–HPβCD and TCS–MβCD complexes exhibited antibacterial properties higher than those of uncomplexed TCS. The two complexes were also found capable of interfering with cell-to-cell communication mechanisms in the C. violaceum model system relying on N-acylhomoserine lactone autoinducers. The inhibitory activity of TCS increased significantly upon inclusion of the drug in HPβCD or MβCD, with small differences between the two CDs. The results obtained suggest that the investigated complexes could be used for treating infections caused by TCS-susceptible pathogens or for preventing biofilm formation on indwelling medical devices such as catheters, stents and orthopedic implants.

Antimicrobial activity of some italian honeys against pathogenic bacteria

Some Italian honeys of different floral origin (acacia, orange, chestnut, coriander, eucalyptus, lime, wildflower) and one honeydew honey were investigated for their potential as natural antimicrobials against pathogens commonly associated with wound or burn infections. S. aureus, S. epidermidis, E. coli, P. aeruginosa and P. mirabilis were used as test microorganisms. The honeys examined showed moderate to high antibacterial activity, with honeydew, eucalyptus and wildflower honeys being the most effective. MIC values obtained by the agar incorporation method were in the range of 5–20% (v/v). Gram-positive bacteria were more susceptible to the inhibitory action of honey, probably because of their larger outer-membrane permeability to exogenous substances. Overall, the results suggest that some of the honeys considered here might have excellent potential for use in antimicrobial formulations for topical applications.

Differential modulation of PPARα and γ target gene expression in the liver and kidney of rats treated with aspirin

Aspirin modified peroxisomal enzymatic activities both in the liver and renal cortex of rats, producing typical effects of peroxisomal proliferators (PPs). Although similar increments in beta-oxidation system and catalase activities were observed in both organs, induction of mRNA-Cyp4a10 and mRNA-FAT/CD36, target genes for peroxisome proliferator-activated receptors alpha (PPARalpha) and gamma (PPARgamma), respectively, was only present in the liver. There was no effect on liver mRNA-PPARalpha, while mRNA-PPARgamma was down-regulated, probably as a result of enzymatic inhibition of cyclooxygenases (COXs) by aspirin which has been shown to decrease the levels of PGJ2 and its metabolites, known as strong endogenous ligands for PPARgamma. Typical PP alterations in cell replication and apoptosis were not found during aspirin treatment or after withdrawal, suggesting that peroxisome proliferation occurs without inducing cell cycle alterations. Probably, the synergic action of both PPARalpha and PPARgamma receptors might reduce the impact on cell proliferation and apoptosis.

Administration of ciprofibrate to lactating mothers induces PPARα-signaling pathway in the liver and kidney of suckling rats

It is well known that the hypolipidemic drug ciprofibrate induces peroxisome proliferation in rodent liver, which in turn leads to the oxidative stress, and modifies some parameters related to cell proliferation and apoptosis. The administration of ciprofibrate to rats during the lactating period determined in their pups significant modifications in hepatic peroxisome enzyme activities, induction of the PPARalpha-target gene, Cyp4a10, and perturbation in cell proliferation and apoptosis, which affected the size of the liver. Moreover, this modification was associated to about two-fold induction of mRNA-PPARalpha. On the contrary, in the kidney, although a similar two-fold up-regulation of PPARalpha was detected, the induction of both peroxisomal enzyme activities and Cyp4a10 were weak, and no alterations were detected, neither in cell cycle nor in the size of the tissue. Our results indicate that the response to ciprofibrate is stronger in the liver than in the kidney of newborn rats.

Experimental investigation of honey as wound repair enhancer by in vitro time-lapse microscopy

a Dipartimento di Ingegneria Chimica, dei Materiali e della Produzione Industriale, Università Federico II, P.le Tecchio 80, 80125 Napoli, Italy. b Dipartimento di Ingegneria Chimica, Materiali e Ambiente, Università “La Sapienza”, Via Eudossiana 18, 00184 Roma, Italy c CEINGE Biotecnologie Avanzate, Via Sergio Pansini, 5, 80131 Napoli, Italy. d Consorzio Interuniversitario Nazionale per la Scienza e Tecnologia dei Materiali (INSTM), UdR INSTM Napoli Federico II, P.le Tecchio, 80, 80125 Napoli, Italy.