Abstract:
Background: An experimental animal model of type 2 diabetes mellitus (T2DM) facilitates the
studying of antidiabetic and antioxidative effects of novel drugs. Feeding high-fat diet (HFD)
followed by a low-dose streptozotocin (STZ) injection is used to induce diabetes and oxidative
changes in the experimental animal model of diabetes.
Objectives: To investigate oxidative and histological changes in the liver of Wistar rats with
T2DM.
Methods: Thirty Wistar rats were divided into five groups as group 1: healthy control, group 2:
HFD control, group 3: HFD for four weeks + STZ (30 mg/kg, ip), group 4: HFD for four weeks
+ STZ (40 mg/kg, ip) and group 5: HFD for four weeks + STZ (50 mg/kg, ip). The liver tissues
were excised from sacrificed animals in all groups and were used for the histological assessment
and biochemical assessment of lipid peroxidation. Malondialdehyde (MDA) concentration in
the liver homogenate was measured using thiobarbituric acid method to assess the level of lipid
peroxidation. Liver tissues were stained in H&E and a semi-quantitative assessment was
conducted to examine histological changes.
Results: The MDA concentration of the healthy control group, HFD control group, STZ-30,
STZ-40 and STZ-50 mg/kg were 15.81 (±2.09), 20.74 (±1.97), 24.27 (±6.20), 32.87 (±1.13),
128.76 (±14.89) nmol/protein (g), respectively. There was a significant increase in MDA
concentration (p˂0.05) in STZ- 40 and STZ-50 mg/kg groups compared to the healthy control
group. The incidence of fatty degeneration, micro and macrovesicular changes, inflammatory
infiltration, and other histological features of STZ induced diabetes mellitus were more
pronounced in rats treated with the highest dose (50 mg/kg) of STZ. Accordingly, the highest
mean histological score (10) was obtained for rats induced with the STZ-50 mg/kg.
Conclusions: STZ-induced oxidative stress, hepatocyte damage and changes in hepatic
morphology were dependent on the dose of STZ. Histological findings corroborated the
biochemical evidence of oxidative stress in high-fat fed low dose STZ induced diabetic rats.
