title: 3-Keto-1,5-bisphosphonates Alleviate Serum-Oxidative Stress in the High-fat Diet Induced Obesity in Rats.
abstract: Obesity has become a leading global health problem owing to its strong association with a high incidence of oxidative stress. Many epidemiologic studies showed that an antioxidant supplementation decreases the state of oxidative stress. In the present work, a HFD-induced rat obesity and oxidative stress were used to investigate the link between fat deposition and serum-oxidative stress markers. We also studied the effect of a chronic administration of 3-keto-1,5-bisphosphonates 1 (a & b) (40 μg/kg/8 weeks/i.p.). Exposure of rats to HFD during 16 weeks induced fat deposition, weight gain and metabolic disruption characterized by an increase in cholesterol, triglyceride and glycemia levels, and a decrease in ionizable calcium and free iron concentrations. HFD also induced serum-oxidative stress status vocalized by an increase in ROS (H2 O2 ), MDA and PC levels, with a decrease in antioxidant enzyme activity (CAT, GPx, SOD). Importantly, 3-keto-1,5-bisphosphonates corrected all the deleterious effects of HFD treatment in vivo, but it failed to inhibit lipases in vitro and in vivo. These studies suggest that 3-keto-1,5-bisphosphonates 1 could be considered as safe antioxidant agents that should also find other potential biological applications.
authors.affiliation: Laboratory of Heteroatom organic chemistry, Department of Chemistry, Faculty of Sciences of Bizerta, University of Carthage, 7021, Jarzouna, Tunisia.
authors.forename: Karima
authors.initials: K
authors.lastname: Lahbib
authors.affiliation: Laboratory of Heteroatom organic chemistry, Department of Chemistry, Faculty of Sciences of Bizerta, University of Carthage, 7021, Jarzouna, Tunisia.
authors.forename: Iyadh
authors.initials: I
authors.lastname: Aouani
authors.affiliation: CNRS, Aix-Marseille University, UMR 7282 Enzymologie Interfaciale et Physiologie de la Lipolyse, 31 Chemin Joseph Aiguier, 13402, Marseille Cedex 20, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Cavalier
authors.affiliation: Laboratory of Heteroatom organic chemistry, Department of Chemistry, Faculty of Sciences of Bizerta, University of Carthage, 7021, Jarzouna, Tunisia.
authors.forename: Soufiane
authors.initials: S
authors.lastname: Touil
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001835:Body Weight; D002784:Cholesterol / Q000097:blood; D059305:Diet, High-Fat / Q000009:adverse effects; D004164:Diphosphonates / Q000138:chemical synthesis / Q000494:pharmacology*; D004195:Disease Models, Animal; D005609:Free Radicals / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D008049:Lipase / Q000037:antagonists & inhibitors; D008297:Male; D009765:Obesity / Q000097:blood* / Q000188:drug therapy*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D000975:Antioxidants; D004164:Diphosphonates; D005609:Free Radicals; D017382:Reactive Oxygen Species; D002784:Cholesterol; D008049:Lipase
keywords: antioxidant enzymes; bisphosphonates; free radicals; lipases; obesity; oxidative stress; pH-stat technique