Pharmacology and Toxicology

Prof. Daniela Curti, Prof. Maurizia Dossena, Prof. Ornella Pastoris, Prof. Marco Peviani

Collaborators: Sara Arnica, Alice Buzzella, Barbara Balestra, Daniela Buonocore, Federica Ferrari, Silvia Molino, Manuela Verri.

Main research topics

– Neuropharmacology (see “Neurobiology”)

 – Pharmacobiochemistry and Toxicology

 

1) Quest for novel antitumor compounds.

Rational design and evaluation of in vitro and in vivo efficacy of newly synthesized  monomeric and dimeric ligands binding sigma-1 and sigma-2 receptors. The research is aimed to identify and optimize new candidate drugs with antitumor activity. In collaboration with: S. Collina and M. Paolillo (Dept. Drug Sciences, UNIPV) (contact: D.Curti).

Prevention of oxiplatin-induced peripheral neuropathy

Randomized phase II study on the efficacy of Superoxide Dismutase + Vitamin E supplementation in patients with colorectal cancer. Oxaliplatin, an antineoplastic platinum-derived compound, is the standard drug used for the treatment of colorectal cancer. However, chronic treatment leads to oxaliplatin-induced peripheral neuropathy. The project aims to investigate the efficacy of patients supplementation with Superoxide Dismutase and Vitamin E to prevent/reduce the oxaliplatin-induced  neurological complications. The oxidative status of the patients over time and the metabolomic profile will be evaluated to identify the molecules involved in the induction and development of the peripheral neuropathy. In collaboration with: S. Brugnatelli (S.C.  Oncologia, Fondazione I.R.C.C.S. Policlinico San Matteo di Pavia); J. Á. Rufián Henares (Dept.  Nutrition and Bromatology, University of Granada, Spain (contact: M. Dossena)

Assessment of the toxicity, antioxidant, antiradical, antinflammatory, immunomodulatory properties and bioavailability of bioactive compounds extracted from vegetables and microalgae.

The study aims to characterize: 1) naringenin, naringin, as well other polyphenols’ content in grapefruit (C. paradisi) zest, rind, pulp, and juice extract; 2) bioactive compounds extracted from fruit/vegetable waste and microalgae such as Scenedesmus and Aphanizomenon flos-aquae (AFA). AFA, also called Klamath Algae, is a cyanobacterium characterized by a unique nutritional profile, containing specific immunomodulatory, anti-inflammatory and antioxidants molecules. In collaboration with: J. Á. Rufián Henares (Dept. Nutrition and Bromatology, University of Granada, Spain); AOP Unolombardia sacpa and Regione Lombardia (contact: M. Dossena).

Metabolism and physical exercise

The energy demands of the human body depend on energy expenditure and basal metabolic rate. The basal metabolic rate is the minimum energy needed to maintain vital functions. During physical exercise, particularly in sports, our metabolism increases and remains at high level for several hours after the end of the training (up to 12 hours). Exercise increases muscle metabolism indirectly through the secretion of anabolic hormones and the accumulation of muscle mass. However, athletes, in comparison with sedentary people, are more exposed to psychophysical stress that leads to release of cortisol and hormonal imbalance; to the increase of free radicals and to muscle, tendon and ligament damage. Our study will evaluate: 1) energy expenditure associated with various types of physical activities; 2) salivary and blood concentrations of hormones and other molecules related to physical activity or sports (e.g. cortisol, testosterone, growth hormone, inflammatory cytokines, ROS); 3) effects of sport food and supplements on exercise performance and post-exercise muscle recovery; 4) change in body composition by the modulation of diet programs (relationship between macronutrients and glycemic load). In collaboration with: G. D’Antona, M. Negro (Centro di Medicina dello Sport,Voghera, UNIPV); I. Fabbri (FIT e MOTOGPTM)  (contact: M. Dossena).

 Gastrointestinal neurobiopathology

Functional gastrointestinal neurobiopathology is studied by evaluating the neuronal control, and its modulation by neurotransmitters, of intestinal motility. The  molecular aspects are investigated by analysing miRNA expression, pharmacogenetics and the influence of the intestinal microbiota in major gastrointestinal disorders such as Celiac disease, Irritable Bowel Syndrome (IBS). Our research interest is also focused on topics related to the pathophysiology of skeletal muscle, especially in the Neuroleptic Malignant Syndrome (NMS). In particular, studies are designed to evaluate the composition of intestinal microbiota in celiac patients using next generation sequencing and to perform genetic and epigenetic analyses in patients with NMS. In collaboration with: Unità di Medicina Interna e Gastroenterologia, Dip. Medicina Interna e Terapia medica UNIPV, Fondazione IRCCS Policlinico San Matteo Unità di Medicina Interna Dip. di Scienze Mediche e Chirurgiche, Università di Bologna, Policlinico S. Orsola-Malpighi; Laboratorio di Tossicologia Clinica e Sperimentale, Centro Antiveleni – IRCCS Fondazione Salvatore Maugeri, Pavia (contact: O. Pastoris).

MRI/PET traceable nanovectors to investigate and modulate neuroinflammatory responses in neurodegenerative disorders

Neuroinflammation is a distinctive marker of pathology that goes along with neuronal demise in several neurodegenerative disorders. Despite neurons are the primary cell type affected in these diseases, accumulating evidences suggest that neuroinflammatory responses actively participate in the pathology and have an impact on the neurodegeneration process.

Our laboratory exploits single-cell transcriptome and functional profiling and novel cell-targeted nanovector platforms (based on MRI/PET traceable polymeric nanoparticles or recombinant AAVs) to obtain better insights into the complexity of glial-cell responses in neurodegenerative diseases and to develop novel drug/gene delivery tools designed for targeted engagement of specific cell subtypes.

Ref. Marco Peviani

Collaborations: Hildegard Buning (Hannover Medical School, Hannover); Nilo Riva (San Raffaele Scientific Institute, Milan); Danilo Pellin (Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, Boston); Alessandra Biffi (University of Padua; Harvard Medical School, Boston); Letterio Salvatore Politi (Humanitas Research Institute, Milan; Boston Children’s hospital); Andrea Protti (Lurie Family Imaging Center, Dana-Farber Cancer Institute, Boston); Daniela Curti (University of Pavia).