Wistar rats with long-term streptozotocin-induced type 1 diabetes mellitus replicate the most relevant clinical, biochemical, and hematologic features of human diabetes / Sobolanii Wistar cu diabet zaharat tip 1 indus cu streptozotocina reproduc cele mai relevante caracteristici clinice, biochimice

Abstract Background: Experimental models are essential for clarifying the pathogenesis of diabetes mellitus (DM). We aimed to provide an exhaustive description of clinical, biochemical, and hematologic features of rats with streptozotocin (STZ)-induced DM. Methods: Wistar rats were assigned to control (n=14) or DM (n=17) groups. DM was induced using STZ (60 mg/kg, i.p.). If STZ failed to induce DM, rats were reinjected with a similar STZ dose. Bodyweight, 24-h food and water intake were measured weekly during 28 weeks. At the end of the study lipid profile, kidney function, and complete blood count were assessed. Results: STZ induced DM in 58.82% of rats. The second STZ administration induced DM in 71.43% of the remaining rats. Diabetics presented progressive, but less significant bodyweight increase than controls, and higher food and water consumption. At the end of the study, diabetics presented higher white blood cells count, glucose, triglycerides, total and low-density lipoprotein cholesterol, and lower creatinine clearance than controls (all p≤0.02). No significant difference was observed between diabetics injected once and those that were reinjected, in any of the studied parameters. Conclusions: This study provides one of the longest follow-ups of rats with STZ-induced type 1 DM, demonstrating that the STZ-diabetic rat replicates the most relevant clinical, biochemical, and hematologic features of human diabetes. The present data also indicate, for the first time, that rats with initial unsuccessful STZ administration can be safely reinjected, with outcomes similar to those seen in rats receiving a single injection. Rezumat Introducere: Modelele experimentale sunt esentiale pentru elucidarea patogenezei diabetului zaharat (DZ). Ne-am propus sa realizam o descriere exhaustiva a caracteristicilor clinice, biochimice si hematologice ale sobolanilor cu DZ indus cu streptozotocina (STZ). Metode: Sobolanii Wistar au fost distribuiti in grupul control (n=14) sau DZ (n=17). DZ a fost indus cu STZ (60 mg/kg, i.p.). Daca STZ nu a indus DZ, sobolanii au fost reinjectati cu o doza similara de STZ. Masele corporale (MC) si consumul de hrana si apa/24h au fost evaluate saptamanal 28 de saptamani. La sfarsitul studiului s-au evaluat profilul lipidic, functia renala si hemoleucograma. Rezultate: STZ a indus DZ la 58,82% dintre sobolani. Reinjectarea a indus DZ la 71,53% din restul sobolanilor. Diabeticii au prezentat o crestere progresiva, dar mai putin importanta a MC comparativ cu sobolanii control si un consum mai important de hrana si apa. La sfarsitul studiului diabeticii au prezentat niveluri mai ridicate ale leucocitelor, glicemiei, trigliceridelor, colesterolului total si LDL-colesterolului si un clearance de creatinina mai redus (p≤0,02). Nu s-a observat nici o diferenta intre diabeticii injectati o singura data si cei reinjectati pentru nici unul dintre parametrii evaluati. Concluzii: Asigurand una dintre cele mai indelungate urmariri ale sobolanilor cu DZ indus cu STZ, acest studiu demonstreaza ca sobolanii diabetici reproduc cele mai relevante caracteristici clinice, biochimice si hematologice ale diabetului uman, dar si ca sobolanii cu injectare ineficienta de STZ pot fi reinjectati in siguranta, avand o evolutie similara cu a celor care au primit o singura administrare.