title: Acute toxicity evaluation of a thiazolo arene ruthenium (II) complex in rats.
abstract: Recently, a series of thiazolo arene ruthenium complexes were found to be highly cytotoxic in vitro, on both cisplatin-sensitive and cisplatin-resistant ovarian cancer cells. The most active compound of the series, [(η(6)-p-cymene)Ru(L)Cl]Cl (L = 1-(2-(2-(3-chlorobenzylidene)hydrazinyl)-4-methylthiazol-5-yl)ethanone), was selected for an in vivo study in order to assess its safety profile. The ruthenium complex was administered to female Crl:WI rats orally, by gastric intubation and intraperitoneal injection. The hematological parameters and the histopathological changes in liver, kidneys, spleen and brain were investigated after a 14-days treatment. The substance was very well tolerated orally, with a LD50 value of over 2000 mg/kg body weight. Symptoms were observed only in the first day after intraperitoneal administration of the highest dose, with a LD50 value between 300 and 2000 mg/kg bw. The hematological profile was not modified at any of the tested doses, after both oral and intraperitoneal acute administration. Structural modifications (moderate lymphocytolysis) were identified only in the spleen at the highest tested dose. In conclusion, the thiazolo arene ruthenium complex was very well tolerated orally and had a low acute toxicity after intraperitoneal administration in Crl:WI rats The results justify further investigation to determine the in vivo therapeutic potential of this promising ruthenium complex.
authors.affiliation: Department of Organic Chemistry, Faculty of Pharmacy, "Iuliu Hatieganu" University of Medicine and Pharmacy, 41 Victor Babes, RO-400012 Cluj-Napoca, Romania. Electronic address: adriana.ignat@umfcluj.ro.
authors.forename: Adriana
authors.initials: A
authors.lastname: Grozav
authors.affiliation: Department of Cell Biology, Histology and Embryology, Faculty of Veterinary Medicine, 3-5 Calea Mănăstur, RO-400372 Cluj-Napoca, Romania. Electronic address: vmiclaus@usamvcluj.ro.
authors.forename: Viorel
authors.initials: V
authors.lastname: Miclaus
authors.affiliation: Department of Pharmacology, Physiology and Physiopathology, Faculty of Pharmacy, "Iuliu Haţieganu" University of Medicine and Pharmacy, 6A, L Pasteur, 400012 Cluj-Napoca, Romania. Electronic address: oliviu.vostinaru@umfcluj.ro.
authors.forename: Oliviu
authors.initials: O
authors.lastname: Vostinaru
authors.affiliation: Department of Pharmacology, Physiology and Physiopathology, Faculty of Pharmacy, "Iuliu Haţieganu" University of Medicine and Pharmacy, 6A, L Pasteur, 400012 Cluj-Napoca, Romania. Electronic address: stelianaghibu@yahoo.com.
authors.forename: Steliana
authors.initials: S
authors.lastname: Ghibu
authors.affiliation: Practical Skills and Experimental Medicine Centre, "Iuliu Haţieganu" University of Medicine and Pharmacy, 8 Victor Babeş, 400012 Cluj-Napoca, Romania. Electronic address: cristi.berce@gmail.com.
authors.forename: Cristian
authors.initials: C
authors.lastname: Berce
authors.affiliation: Clinic of Obstetrics and Gynecology, Department Mother and Baby, University of Medicine and Pharmacy "Iuliu Hatieganu", Cluj-Napoca, Romania. Electronic address: cristina.rotar@umfcluj.ro.
authors.forename: Ioana
authors.initials: I
authors.lastname: Rotar
authors.affiliation: Department of Pharmacology, Physiology and Physiopathology, Faculty of Pharmacy, "Iuliu Haţieganu" University of Medicine and Pharmacy, 6A, L Pasteur, 400012 Cluj-Napoca, Romania. Electronic address: cmogosan@umfcluj.ro.
authors.forename: Cristina
authors.initials: C
authors.lastname: Mogosan
authors.affiliation: Institut de Chimie, Université de Neuchâtel, 51 Avenue de Bellevaux, CH-2000 Neuchâtel, Switzerland. Electronic address: bruno.therrien@unine.ch.
authors.forename: Bruno
authors.initials: B
authors.lastname: Therrien
authors.affiliation: Department of Toxicology, Faculty of Pharmacy, "Iuliu Haţieganu" University of Medicine and Pharmacy, 8 Victor Babeş, 400012 Cluj-Napoca, Romania. Electronic address: floghin@umfcluj.ro.
authors.forename: Felicia
authors.initials: F
authors.lastname: Loghin
authors.affiliation: Department of Toxicology, Faculty of Pharmacy, "Iuliu Haţieganu" University of Medicine and Pharmacy, 8 Victor Babeş, 400012 Cluj-Napoca, Romania. Electronic address: dpopa@umfcluj.ro.
authors.forename: Daniela-Saveta
authors.initials: DS
authors.lastname: Popa
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000633:toxicity*; D015415:Biomarkers / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D007274:Injections, Intraperitoneal; D007928:Lethal Dose 50; D023421:Models, Animal; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000633:toxicity*; D017208:Rats, Wistar; D018570:Risk Assessment; D017975:Ruthenium Compounds / Q000008:administration & dosage / Q000633:toxicity*; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D013997:Time Factors; D023382:Toxicity Tests, Acute / Q000379:methods*
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D009942:Organometallic Compounds; D017975:Ruthenium Compounds
keywords: Acute toxicity; Arene ruthenium complexes; Thiazole