الفهرس 
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Abstract
The aim of the present investigation was to study the effect of
dapagliflozin treatment on glycemic state, lipid profile, renal functions, renal
histopathology and some underlying possible mechanisms in type 2 diabetic rats.
To achieve this aim, fifty adult male albino rats were used. Rats were
divided equally into five experimental groups: non-diabetic, diabetic non-treated,
diabetic metformin-treated, diabetic dapagliflozin-treated & diabetic combined
metformin and dapagliflozin -treated.
By the end of the experimental period (4 weeks), 24-h urine sample was
collected for each rat alone using the metabolic cage and urine volume (ml/min)
was calculated. Then urine samples were centrifuged and stored at -20°C until
needed for subsequent analysis & estimation of urinary creatinine, urinary
albumin & urinary NAG. In the next day, overnight-fasted rats were anesthetized
and the anterior abdominal wall was opened and midline laparotomy was done,
after cleansing the skin and shaving the hair. Renal artery was exposed to
measure RBF velocity and RVR using Doppler technique. Then, fasting blood
samples were collected directly from the abdominal aorta using sterilized plastic
fine cannulae in 2 clean graduated tubes the first was EDTA tube for estimation
of HbA1c and the second was plain that was left for clotting then centrifuged and
the supernatant serum was collected and frozen in dry tubes at -20°C until needed
for subsequent analysis & estimation of fasting serum glucose, insulin, TC, TG,
HDL-C, renal function tests (BUN, serum creatinine, serum cystatin C), TAC,
MDA & TNF- . Then, HOMA-IR, LDL-C & creatinine clearance were
calculated. Finally, both kidneys were excised and fixed in 10% formalin then
prepared for H&E and Mallory trichrome staining and histopathological
examination under a light microscope.
In the present investigation, it was found that fasting serum glucose,
HbA1c, serum insulin, HOMA-IR, TC, TG, LDL-C, BUN, serum creatinine,
serum cystatin C, urinary albumin, urinary NAG, MDA, TNF- and RVR were
significantly higher; while HDL-C, creatinine clearance, TAC and RBF velocity
were significantly lower in diabetic non-treated group when compared to the
corresponding values of non-diabetic group.
The diabetic metformin-treated group revealed statistical significant
reduction of fasting serum glucose, HbA1c, fasting serum insulin, HOMA-IR,
TC, TG, LDL-C, BUN, serum creatinine, serum cystatin C, urinary NAG, serum
TNF-, serum MDA and RVR; insignificant change in urinary albumin and
statistical significant elevation of HDL-C, creatinine clearance, TAC and RBF
velocity when compared to the corresponding values of diabetic non-treated
group.
The diabetic dapagliflozin-treated group revealed statistical significant
reduction of fasting serum glucose, HbA1c, serum insulin, HOMA-IR, TG, TC,
LDL-C, BUN, serum creatinine, serum cystatin C, urinary albumin, urinary NAG,
TNF-, MDA and RVR and statistical significant elevation of HDL-C, creatinine
clearance, TAC and RBF velocity when compared to the corresponding values of
diabetic non-treated group.
Upon comparing the results of diabetic dapagliflozin-treated group to that
of diabetic metformin -treated group, it was found that fasting serum glucose, HbA1c, fasting serum insulin, HOMA-IR, TC, TG, LDL-C, BUN, serum
creatinine, serum cystatin C, urinary NAG, serum TNF- and RVR were
significantly lower while HDL-C, creatinine clearance, TAC and RBF velocity
were significantly higher;. However urinary albumin and serum MDA level were
statistically insignificant.