Abstract:
Aim: To investigate vascular endothelial growth factor (VEGF) and proliferating cell nuclear
antigen (PCNA) immunoreactivities, as well as apoptosis and oxidative stress levels in
streptozotocin (STZ)-induced diabetic rats, and determine how Neferine affected these parameters.
Design: A four-week prospective experimental study
Methods: 35 male Sprague Dawley rats aged 8-10 weeks and weighing 200-250 g were divided
into five groups of seven. Fasting blood glucose was measured 72 hours after intraperitoneal
injection of a single 60mg/kg STZ dose dissolved in 0.4ml (0.1 M) sodium-citrate buffer (pH:4.5)
to 21 rats for DM induction, with values >250 mg/dl considered diabetic. Following experimental
DM induction, (a) Group 2 (Sham group) received daily intraperitoneal 0.25 ml/kg 0.9% normal
saline throughout the experiment; (c) Group 4 (DM plus Bevacizumab) received a single
intraperitoneal 0.01mL (2.5 mg/kg) Bevacizumab injection, followed by daily intraperitoneal 0.25
mL/kg 0.9% normal saline throughout the experiment; and (d) Group 5 (DM plus Neferine)
received daily intraperitoneal 4 mg/kg Neferine throughout the experiment. While Group 1
(control) received no treatment, normal healthy rats in Group 3 (Neferine) received daily
intraperitoneal 4 mg/kg Neferine throughout the experiment. The total antioxidant capacity (TAS)
and total oxidative stress (TOS) levels in serum and eye tissue homogenates were evaluated using
ELISA. Immuno-histochemical staining for PCNA and VEGF was performed, and apoptotic cells
were determined using TUNEL method.
Results: In comparison to group IV, group V had significantly higher TAS and lower TOS in
serum and eye tissue homogenates (p<0.05 for both). Despite significantly lower VEGF levels and
apoptotic cells (p<0.05 for both), there was no significant change in PCNA levels in group V
(p>0.05).
Conclusions: DM was associated with significantly decreased TAS in retinal tissue, increased
TOS and apoptotic cells, as well as VEGF and PCNA immunoreactivities. Neferine altered
parameters other than PCNA in the opposite direction, demonstrating a reductive effect on DM.
