Obesity and peripheral neuropathy risk: comparison of sciatic nerve alterations in rats fed with a high-fat diet and in obese Zucker rats.

Obesity, diabetes and metabolic syndrome are connected to neu-ropathy onset risk. However, studies that have investigated thecontribution of the single component revealed mixed results.We aimed to compare the nerve fiber changes of the sciatic nervein a diet-induced obese (DIO) rats and leptin receptor-deficientobese Zucker rats (OZRs). After five weeks with a high-fat diet OZRssignificantly increases the risk for peripheral neuropathy.PRECLINICAL AND CLINICAL EVALUATIONS OF THEEFFICACY OF RACEMIC AND DEXTROROTATORY FORMSOF THIOCTIC ACID IN NEUROPATHIC PAIND. Tomassoni1, L. Di Cesare Mannelli2, E. Trallori2, A. Pacini3, C. Ghelardini2, F. Pipino4, G. Buzzi4, M. Poma4, F. Francese4, E. Traini5, F. Amenta51School of Biosciences and Veterinary Medicine, University ofCamerino; 2Department of Neuroscience, Psychology, DrugResearch and Child Health, Pharmacology and ToxicologySection, University of Florence; 3Department of Experimentaland Clinical Medicine, Anatomy and Histology Section, Universityof Florence; 4Santa Rita Clinic, Vercelli; 5School of Pharmacy,Human Anatomy Section, University of Camerino, ItalyCompressive pain, radiculopathy, low back pain are heterogeneousdisorder including patients with dominant nociceptive, inflammato-ry and neuropathic pain. Selected antioxidants have been proposedas potential therapeutic agents in the treatment or prevention ofthese pathologies strongly related to redox unbalance. Thioctic acidis an antioxidant existing in nature and expressed in two opticalisomers. The present study assessed in preclinical model of com-pression of sciatic nerve, induced by loose ligation, and in a clinicaltrial, the possible neuroprotective role of racemic and dextro-rota-tory forms of thioctic acid.Loose ligation of the right sciatic nervewas performed in spontaneously hypertensive rats (SHR), used asa model of increased oxidative stress, and in normotensive Wistar-Kyoto rats (WKY) used as a control group. Animals with sciaticnerve ligation were left untreated or were treated intraperitoneallyfor 14 days with intraperitoneal injection of different dose ofracemic (rac) and two enantiomers form [R(+) and S(-)] of thioc-tic acid. Control SHR and WKY rats received the same amounts ofvehicle.Treatment with thioctic acid preserves the structure of thedistal portion of sciatic nerve. In the spinal cord, antioxidant treat-ment reduced oxidative stress and astrogliosis developed followingloose ligation. R(+)-thioctic acid was more active than rac or S(-).The clinical trial has showed a greater influence on painful symp-tomatology, a quicker recovery and a better impact on quality oflife of R(+) vsrac. The results of preclinical and clinical studiessuggest that thioctic acid, with particular reference to its R(+)enantiomer, may have a place in the treatment of neuropathies. (HFD), ad libitum, DIO rats developed obesity. The rats werestudied for the other 12 weeks of HFD. Animals fed with stan-dard diet were used as controls (CHOW rats). Both the OZRs andDIO rats had a significant increase in body weight compared tothe lean Zucker rats (LZRs) and CHOW, respectively.Morphological, immunochemical, and immunohistochemicaltechniques were performed. Blood pressure, glycemia, and insulinlevels were higher in both DIO rats and OZRs in comparison toCHOW and LZRs. No difference in total cholesterol and triglyc-erides levels was observed in DIO rats. On the contrary, the OZRswere characterized by hyperlipidemia. Morphometric results didnot reveal differences in myelin thickness and axonal area of thenerve fibers. Immunohistochemical analysis of the sciatic nervein obese rats compared to the controls evidenced reduced expres-sion of neurofilament (NF). Moreover, a lower expression of themyelin basic protein (MBP) was observed in the sciatic nerve ofobese animals. Our data showed an increased interleukin-1 beta(IL-1β) expression in both obese animal models. Besides,increased levels of oxidized proteins were found in obesity.These findings suggest that the concomitant presence of hyper-tension, inflammation and oxidative stress in DIO rats and OZRssignificantly increases the risk for peripheral neuropathy