Ormesi
L’ormesi è una funzione adattativa caratterizzata da una risposta bifasica dose-dipendente, che si manifesta come conseguenza dell’esposizione a un range molto ampio di stimoli. I meccanismi di controllo omeostatico e ormetico sono presenti in tutti i sistemi biologici, rispondono autonomamente a cambiamenti di stato o ad alterazione di meccanismi regolati indotti da agenti esogeni (Amendola, Cerioli, Migliore, 2006. Ormesi: la rivoluzione dose-risposta. Monografie APAT, pp. 1-30). Le risposte ormetiche, in genere, mostrano una modesta stimolazione alle basse dosi (maggiore del 30-60% del controllo) e un’inibizione alle alte dosi. Perciò, per soddisfare la definizione “qualitativa” dell’ormesi, devono necessariamente essere presenti sia la dimensione stimolatoria sia quella inibitoria. La curva di risposta ormetica può essere rappresentata da una parabola, una U dritta o rovesciata, in relazione all’endpoint considerato: si ottiene una risposta a U diritta se si misura un danno all’organismo (ad es. l’aumento della mortalità), l’alterazione di qualche funzione fisiologica o l’incidenza di malattie (come il cancro o le malattie cardiovascolari); si ottiene una risposta a U rovesciata se si misurano funzioni fisiologiche, come accrescimento o sopravvivenza. Gli studi sull’ormesi, iniziati nel nostro laboratorio intorno agli anni ’90, sono stati effettuati su diversi sistemi biologici. I più recenti includono batteri e piante esposte alla contaminazione da antibiotici, farmaci presenti nei comparti ambientali perché ampiamente utilizzati in zootecnia intensiva. Per quanto riguarda le piante, è stato dimostrata la risposta ormetica sia in laboratorio (Lythrum salicaria) sia sul campo (Zea mays). Inoltre, antibiotici differenti sono in grado di attivare questa risposta. Per quanto riguarda i microrganismi, è stata dimostrata la risposta ormetica di un ceppo di riferimento di E. coli (MG1655) esposto a basse concentrazioni di Tetraciclina. I lavori sull'ormesi sono stati finanziati da Regione Emilia Romagna (Grant. n. LR 28/98-PSA 2005 in collaborazione con CRPA - Centro di Ricerca sulle Produzioni Animali, Reggio Emilia e Istituto Superiore di Sanità) e APAT (ora ISPRA).
Migliore L., Rotini A., Thaller M.C. (2013). LOW DOSES OF TETRACYCLINE TRIGGER THE E. COLI GROWTH: A CASE OF HORMETIC RESPONSE. Dose Response, 11(4): 565-572. DOI: 10.2203/dose-response.13-002.Migliore
Hormesis is a biphasic dose-response relationship, occurring when low concentrations of toxic agents elicit apparent improvements. In this work, the ability of sub-inhibitory concentrations of Tetracycline to induce hormetic response in a model organism was investigated. To this aim a reference strain of Escherichia coli, MG1655, was exposed to six decreasing doses of Tetracycline (between 0.00375 and 0.12 μg/ml), much lower than the Minimal Inhibitory Concentration (4 μg/ml). An hormetic increase was observed at the intermediate concentrations (0.015-0.03 μg/ml) of the tested range. The Colony Forming Unit number, indeed, rose up to 141% and 121% as compared to the control. At the highest (0.00375 μg/ml) and lowest (0.12 μg/ml) concentrations a slight decrease in CFU number was found. Results demonstrated that, in Escherichia coli, low concentrations of Tetracycline bias the bacterial numerical increase through a hormetic response; the dose-response curve describing this numerical increase is an U-inverted curve. Furthermore, these data confirm that hormesis is common to many - if not all - living systems, including bacteria, and underline the relevance of a deepened knowledge of both the effects and the possible consequences of exposure to low doses of contaminants.
Migliore L., Rotini A., Cerioli N.L., Cozzolino S., Fiori M. (2010). PHYTOTOXIC ANTIBIOTIC SULFADIMETHOXINE ELICITS A COMPLEX HORMETIC RESPONSE IN THE WEED LYTHRUM SALICARIA L. Dose Response, 8(4): 414-427. DOI: 10.2203/dose-response.09-033.Migliore
In order to evaluate the hormetic response of the weed Lythrum salicaria to drug exposure we investigated the effects of the antibiotic Sulfadimethoxine by growing Lythrum plants for 28 days on culture media containing different drug concentrations (between 0.005 and 50 mg.L-1). The antibiotic was absorbed by plants and can be found in plant tissue. The plant response was organ-dependent: roots, cotyledons and cotyledon petioles, were always affected by a toxic effect, whilst internodes and leaves length, showed a variable dose-depending response, with an increased growth at the lower drug concentrations and toxic effects at the higher ones. This variable response was probably dependant on different levels of local contamination resulting from a balance between accumulation rate and drug dilution in the increasing plant biomass. As a consequence, drug toxicity or hormetic response varied according to concentration and were different in each of the examined plant organ/tissue. Thus, even if hormesis can be considered a general plant response, each plant organ/tissue responds differently, depending on the local drug concentration and exposure time.
Migliore L., Godeas F., De Filippis S.P., Mantovi P., Barchi D., Testa C., Rubattu N., Brambilla G. (2010). HORMETIC EFFECT(S) OF TETRACYCLINES AS ENVIRONMENTAL CONTAMINANT ON ZEA MAYS. Environmental Pollution, 158(1): 129-134. doi:10.1016/j.envpol.2009.07.039
Animal wastes from intensive pig farming as fertilizers may expose crops to antimicrobials. Zea mays cultivations were carried out on a virgin field, subjected to dressing with pig slurries contaminated at 15 mg L 1 of Oxy- and 5 mg L 1 of Chlor-tetracycline, and at 8 mg L 1 of Oxy and 3 mg L 1 of Chlor, respectively. Pot cultivation was performed outdoor (Oxy in the range 62.5–1000 ng g 1 dry soil) and plants harvested after 45 days. Tetracyclines analyses on soils and on field plants (roots, stalks, and leaves) did not determine the appreciable presence of tetracyclines. Residues were found in the 45-day pot corn only, in the range of 1–50 ng g 1 for Oxy in roots, accounting for a 5% carry-over rate, on average. Although no detectable residues in plants from on land cultivations, both experimental batches showed the same biphasic growth form corresponding to a dose/response hormetic curve.