Thesis (M.Sc.) -Cairo University, 2024.

Bibliography: pages 115-160.

Acute kidney injury (AKI) affects 25% of children and 15% of adults
who are hospitalized. Therefore, the present investigation aimed to evaluate the
possible therapeutic potency of ZnO-chitosan nanoparticles against acute kidney
injury induced by gentamicin (GM) in rats. In the present work, twenty-four
male Wistar albino rats weighing 140 ± 10 gm were used in the experiment. The
obtained results in the present study could be summarized as the following:-
1) The physicochemical characterization of chitosan and zinc oxide-
chitosan nanoparticles (ZnO-CS NPs) showed:
a- The results of UV-Vis spectroscopy showed that the characteristic
peak of chitosan was found to be 230 nm. ZnO nanoparticles have been
incorporated into a chitosan matrix, as evidenced by the presence of an
absorption band at 300 nm.
b- The X-ray diffractometer (XRD) spectra revealed that chitosan
polymer's typical peak was 20.17° because of the numerous hydrogen
bonds formed between the amine, hydroxyl, and other functional
groups within the molecule. The XRD spectrum of ZnO-CS NPs
revealed significant diffraction peaks at 2θ values of 31.8°, 34.5°, 36.3°,
47.6°, 56.7°,62.9°, 68.1°, and 69.1°. Planes have been sharply linked
to the hexagonal wurtzite-type structure or zincite phase of ZnO,
coupled by a low-intensity peak at 2θ = 20.2° attributable to the
crystalline lattice of the chitosan.
c- The transmission electron microscope (TEM) analysis showed that
the size of the chitosan particles was in the range of 750 nm, whereas
the ZnO-CS NPs that were generated had a spherical structure with an
average diameter of 30.68 nm.
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Summary
d- FTIR spectroscopy showed that chitosan absorbs at 3340 cm−1 due
to the stretching vibrations of the NH2 and OH groups. The larger and
stronger peak moved significantly to a lower wave number at 3400
cm−1, showing extensive interaction between these groups and ZnO,
when compared to chitosan. The asymmetric stretching of CH3 and
CH2 of chitosan polymer is responsible for the absorption peaks at
2900, 2820 cm−1. The -NH2 group's bending vibration and the C-O
stretching group are responsible for the absorption maxima at 1650 and
1090 cm−1 are ascribed to the bending vibration of –NH2 group and C–
O stretching group. Absorption peaks at 651 cm−1 and 459 cm−1 are
new in comparison to chitosan and are caused due to attachment of the
amide group and ZnO stretching mode.
2) Present study revealed that the final body weight of GM-treated rats
decreased at the end of the trail. On the other hand, administration of
ZnO-CS NPs (30 and 60 mg/kg body weight, respectively)
increased the final body weight of rats.
3) When the GM-treated rats were compared to the control group, a
significant increase (P<0.05) in relative kidney weight was observed.
Whereas, oral administration of ZnO-CS NPs (30 and 60 mg/kg
body weight, respectively) decreased the relative kidney weight of
rats as compared to the GM group.
4) Rats treated with GM had higher serum and urine creatinine
concentrations than rats in the control group. While, a significant
decrease (P<0.05) was recorded in the serum and urine creatinine
concentrations after ZnO-CS NPs (30& 60 mg/kg body weight) oral
administration as compared to the GM group.
111
Summary
5) A significant decrease (P<0.05) in creatinine clearance was observed
in GM-treated rats. On the other hand, a significant increase (P<0.05)
in creatinine clearance was observed after oral administration of
ZnO-CS NPs (30& 60 mg/kg body weight, respectively), as
compared to the GM group.
6) The serum and urine urea concentrations of GM-treated rats showed
a significant increase (P<0.05). Whereas a significant decrease in
serum and urine urea concentrations was observed after oral
administration of ZnO-CS NPs (30& 60 mg/kg body weight,
respectively), as compared to the GM group.
7) The serum and urine uric acid concentrations of GM-treated rats
increased as compared to the control group. However, a decline was
observed after ZnO-CS NPs (30& 60 mg/kg body weight,
respectively) treatment as compared to the GM group.
8) A significant increase in the microalbumin concentration of GM-
treated rats as compared to the control group. Whereas, oral
administration of ZnO-CS NPs (30& 60 mg/kg body weight,
respectively) caused a significant decrease in microalbumin
concentration as compared to the GM group.
9) The serum and urine potassium concentrations of GM-treated rats
showed a significant increase as compared to the control group.
While, a significant decrease was noticed in serum and urine
potassium concentrations of rats treated orally with ZnO-CS NPs (30
&60 mg/Kg body weight) as compared to the GM group.
10) The serum and urine chloride concentrations increased significantly
in GM-treated rats as compared to the control group. While, a
significant decrease was recorded in serum and chloride
concentrations of ZnO-CS NPs-treated rats (30& 60 mg/kg body
weight, respectively), as compared to the GM group.
112
Summary
11) A significant increase in the serum and urine sodium concentrations
of GM-treated rats as compared to the control group. While oral
administration of ZnO-CS NPs (30& 60 mg/kg body weight,
respectively) caused a significant decrease in sodium concentrations
as compared to the GM group.
12) The MDA concentration of GM-treated rats showed a significant
increase as compared to the control group. On the other hand, a
significant decrease in MDA concentration was observed in ZnO-CS
NPs orally treated rats (30& 60 mg/kg body weight, respectively) as
compared to the GM group.
13) A significant decrease in the GSH concentration of GM-treated rats
as compared to the control group. Despite, a significant increase was
noticed in the GSH concentration of ZnO-CS Nps treated rats (30&
60 mg/kg body weight, respectively) as compared to the GM group.
14) Kidney NO concentration in GM rats decreased significantly as
compared to the control group. However, a significant increase in
Kidney NO concentration was observed after ZnO-CS NPs oral
administration (30& 60 mg/kg body weight, respectively) as
compared to GM groups.
15) The kidney CAT activity in GM-treated rats showed a significant
decrease, as compared to the control group. Furthermore, a
significant increase in kidney CAT activity was noticed in ZnO-CS
Nps treated rats (30& 60 mg/kg body weight, orally) , as compared
to the GM group.
16) A significant decrease in GST activity in GM rats as compared to the
control group. While, a significant increase was recorded in GST
activity of ZnO-CS Nps treated rats (30 &60 mg/Kg body weight,
orally) as compared to the GM group.
113
Summary
17) The kidney SOD activity in GM-treated rats decreased significantly
as compared to the control group. While, a significant increase in
SOD activity was observed after ZnO-CS Nps oral administration
(30& 60 mg/kg body weight, respectively), as compared to the GM
group.
18) Histopathological study of the kidneys of the gentamicin group
showed severe shrinking and degeneration of glomeruli with
deformed renal tissue architecture. Whereas, the treatment with
ZnO-CS NPs (30 &60 mg/Kg body weight) caused marked
regeneration in glomerulus and Bowman’s capsule with normal renal
tissue architecture.

يهدف البحث الحالي إلى تقييم الفعالية العلاجية المحتملة لجزيئات أكسيد الزنك-كيتوزان النانوية ضد إصابة الكلى الحادة التي يسببها الجنتاميسين في الجرذان. في العمل الحالي ،تم استخدام أربعة وعشرين من ذكور جرذان بيضاء وزنها 140±10جم وتم تقسيمهم الي أربع مجموعات. ويمكن تلخيص النتائج التي توصلت إليها الدراسة في النقاط التالية:
1. أظهرت دراسة الخصائص الفيزيوكيميائية للكيتوزان وجزيئات أكسيد الزنك-كيتوزان النانوية التالي:
أ- يُظهر تحليل طيف الامتصاص المرئي للأشعة فوق البنفسجيةأن جزيئات أكسيد الزنك النانوية تم دمجها في مصفوفة الكيتوزان،كما يتضح من وجود شريط امتصاص عند 300 نانومتر.
ب- أثبت تحليل حيود الأشعة السينية (XRD) أن جزيئات أكسيد الزنك-كيتوزان النانوية لديها طبيعة متبلورة. ج-أظهر تحليل المجهر الإلكتروني النافذ ((TEMأن حجم جسيمات الكيتوزان كانت في حدود 750 نانومتر،في حين أن جزيئاتأكسيدالزنك-كيتوزانالنانوية كان لها هيكل كرويبمتوسط قطريبلغ 30.68 نانوميتر.
د- أظهر التحليل الطيفي للأشعة تحت الحمراء بتحويل فورييه(FTIR) المجموعات الوظيفية الخاصة بالكيتوزان وجزيئاتأكسيدالزنك-كيتوزان النانوية.
2. أظهرت الدراسة الحالية أن وزن الجسم النهائي للجرذان المعالجة بالجينتاميسين انخفض بشكل ملحوظ في نهاية التجربة. من ناحية أخرى، أدى إعطاء جزيئات أكسيد الزنك-كيتوزان النانوية(30 و 60 مجم / كجم من وزن الجسم، على التوالي)إلى زيادة وزن الجسم النهائي للجرذان.
3. لوحظ زيادة معنويةفي الوزن النسبي للكلية في الجرذان المعالجة بالجينتاميسين. في حين أن تناول جزيئاتأكسيدالزنك-كيتوزان النانويةعن طريق الفم (30 و 60 مجم / كجم من وزن الجسم، على التوالي) أدى إلى انخفاض الوزن النسبي للكلية للجرذان.
4. الجرذان التي عولجت بالجينتاميسين كان لديها تركيز أعلى من الكرياتينين في الدم والبول. بينما سجل انخفاض معنوي في تركيز الكرياتينين في الدم والبول بعد تناول جزيئات أكسيد الزنك-كيتوزان النانوية (30 و 60 مجم / كجم من وزن الجسم، على التوالي)عن طريق الفم.

Issues also as CD.

Text in English and abstract in Arabic & English.