4. RESULTS - bu.edu.eg · The preceptation of calcium salt (mineralization) in placenta was also reported as shown in figure (26). 4.1.3. Standard curves of enrofloxacin:

…..……………….………………..….…………………………… Results

-82-

4. RESULTS

The teratogenic effects of enrofloxacin and levofloxacin produced

in fetuses following administration to female pregnant rats from 6th

to 15th

day of gestation were compared with those of control fetuses from the

non-treated mother. Also, the histopathological changes, serum and tissue

concentrations of the drugs in mothers and fetuses were also studied.

4.1. Enrofloxacin.

4.1.1. Teratogenic effect: Oral administration of enrofloxacin in

therapeutic dose (10 mg / kg b.wt) and double therapeutic dose (20 mg /

kg b.wt) to pregnant female rats from 6th

to 15th

day of gestation period.

Highly significant decrease in number of fetuses per mother and highly

significant decrease in number of viable fetuses were recorded following

administration of both doses of enrofloxacin. The obtained results

revealed that enrofloxacin produced a highly significant increase in

number of resorbed fetuses per mother (Table 1 and Figure 1).

The effect of both given doses of enrofloxacin on fetal body weight

and length are tabulated in table (2) and shown in figure (2). Both fetal

body weight and length showed highly significant decrease when

compared with the data of control group. This indicated that therapeutic

dose of enrofloxacin (10 mg/kg b.wt) and double therapeutic dose (20 mg

/ kg b.wt) retard growth of developing fetuses during the period of

gestation.

The therapeutic dose of enrofloxacin (10 mg/kg b.wt) resulted in

diverticulum dilatation of the brain in 20%, thymus hypoplasia in 24.0%;

pulmonary hypoplasia in 52%, cardiac enlargement in 44%; hepatomegaly

in 56% ; kidney hypotrophy with dilatation of renal pelvis either

Results …………………..………………………………………….…...

-83-

unilateral or bilateral in 76% and decrease or small in size of suprarenal

gland in 12% (Table 3 and Figures 3, 4, 5, 6, 7 and 8).

Oral administration of double therapeutic dose of enrofloxacin (20

mg/kg b.wt) to pregnant rat from 6th

to 15th

day of gestation period

induced diverticulum dilatation of brain in 30%; thymus hypoplasia in

35.0% pulmonary hypoplasia in 75%; cardiac enlargement in 60.0%;

hepatomegaly in 65.0% atrophy or small in size of the kidney in 85% but

some cases showed complete absence of kidney with suprarenal gland

with unilateral or bilateral dilatation of renal pelvis and decrease or small

in size of suprarenal gland in 20% (Table 4 and Figures 9, 10 and 11).

Skeletal examinations of fetuses obtained from mothers given

orally enrofloxacin in therapeutic dose (10 mg/kg b.wt) from 6th

to 15th

day of gestation period showed impaired ossification of skull in 18.75%;

absence of sternebra in 62.5% as complete absence of 1st, 3

rd, 5

th and 6

th

sternebra or small in size of 2nd

, 4th

and 5th

. Other cases showed broken

dispersed sternebra. Absence of digit’s bone of fore and hind limb were

recorded 50.00 %; absence of some metatarsal bone in 25.00% and some

metacarpal bone in 31.25%, absence of some bone of caudal vertebrae in

56.25% of examined fetuses as shown in table (5) and Figures (12, 13 and

14).

Administration of double therapeutic dose of enrofloxacin (20

mg/kg b.wt) to pregnant rats resulted in impaired ossification of skull in

28.57%; absence of sternebra in 85.7%. Some cases showed complete

absence of all sternebra while others showed complete absence of 1st, 2

nd,

3rd

, 4th

, 5th

and 6th

with small in size of 2nd

, 3rd

, 4th

. Absence of digit’s

bone of fore and hind limb were recorded in 64.28%, absence of some

metatarsal bone in 71.4% and some of metacarpal bone in 57.14%,

…..……………….………………..….…………………………… Results

-84-

complete absence of caudal vertebrae with ischial bone in 92.85% of

examined fetuse as shown in table (6) and Figures (15 and 16).

4.1.2. Histopathological examination:

Histopathological examination of brain, lung, liver, kidney, spleen,

intestine, heart, uterus and placenta of the pregnant female rats

administered therapeutic dose of enrofloxacin (10 mg/kg b.wt) from 6th

to

15th

day of pregnancy revealed some pathological lesions in mothers. The

lung showed thickening in wall of blood vessels due to muscular

hypertrophy, other cases showed focal aggregation of mononuclear cell

with alveolar emphysema as shown in figure (17 and 18).The brain

showed odema with glaiosis (figure 19). The spleenic tissue showed

lymphoid deplation with excessive haemosiderosis (Figure 20).

Hyalinization of cardiac muscle was recorded also in figure (21).

Degenerative changes of hepatocytes with vacuolar and hydropic

degeneration of the hepatic tissue (Figure 22). Cloudy swelling of the

kidney, cattarhal enteritis, activation of goblet cells with inflammatory

cellular infiltration in the propria and submacosa of the lumen of intestine

were recorded in tissues of rats administered 10 mg / kg b.wt of

enrofloxacin orally and once daily from 6th

to 15th

day of pregnancy.

Administration of double therapeutic dose of enrofloxacin (20 mg /

kg b.wt) showed histopathological lesions represented by increase

incidence of pathological effects than recorded in therapeutic dose as

excessive degeneration with necrosis of hepatocytes, prevascular

lymphocytic aggregation of the kidney (Figure 23), excessive lymphoid

deplation with excessive haemosiderosis of spleen and hyalinization in

cardiac muscle. Excessive glaiosis of the brain were showed.

Histopathological changes in the uterus and placenta mainly occur with

double therapeutic dose as edematous hypertrophy of the chorion but

Results …………………..………………………………………….…...

-85-

some cases showed desuqmation of the endometerial gland and

epithelium of the uterus (Figures 24 and 25). The preceptation of calcium

salt (mineralization) in placenta was also reported as shown in figure

(26).

4.1.3. Standard curves of enrofloxacin:

Concentration of 0.025, 0.05, 0.1, 1.0, 1.25 (reference

concentration), 2.5, 5.0, 10.0 mg of enrofloxacin per milliliter phosphate

buffer (pH 7.2) or normal rat’s serum as well as their corresponding zone

of inhibition were illustrated in table (7) and shown in figure (27).

4.1.4. Serum and tissue concentration of enrofloxacin:

Following oral administration of therapeutic and double therapeutic

dose of enrofloxacin once daily. Serum and tissue concentrations of

therapeutic dose of enrofloxacin following (10 mg/kg b.wt) once daily

were represented in table (8) and shown in figure (29). These data

revealed distribution of the drug in tested tissue (brain, lung, heart, liver,

spleen, kidney, thigh and thoracic muscle, fat, skin and whole fetuses).

The data revealed that the liver and kidney contained the highest drug

concentrations (0.48 ± 0.0085 and 0.33 ± 0.0167 g/gm respectively) in

rats slaughtered at 10th

day of pregnancy. On other hand, the lowest

concentrations were recorded in fetuses and brain (0.115 ± 0.0043 and

0.088 ± 0.0018 g/gm respectively). The data reported for the rats

slaughtered at 16th

day of pregnancy (24 hours after last dose

administration) reported that the liver, kidney, lung and skin contained

the most highest concentrations as 0.79 ± 0.0191, 0.69 ± 0.0102, 0.53 ±

0.0116 and 0.44 ± 0.0058 g/gm respectively. The whole fetuses and the

brain contained the lowest concentrations of enrofloxacin (0.163 ± 0.0056

and 0.18 ± 0.0056 g/gm respectively). The data resulted from the rats

…..……………….………………..….…………………………… Results

-86-

slaughtered at 20th

day of pregnancy (5 days post drug administration, the

drug can not be assayed in all tissues except liver and kidney which

contained low concentrations (0.047 ± 0.0093 and 0.035 ± 0.0017 g/gm

respectively) as shown in table (8) and figure (28).

The serum and tissue concentrations following administration of

double therapeutic dose of enrofloxacin (20 mg/kg b.wt) were recorded in

table (9) and figure (29). The data revealed that high concentration of the

drug after double therapeutic administration were assayed in liver, kidney

and lung of slaughtered rats at 10th

day of pregnancy (0.54 ± 0.00 47,

0.449 ± 0.0052 and 0.35 ± 0.0091 g/gm respectively). Fetuses, brain and

spleen contained the lowest concentrations (0.169 ± 0.0048, 0.12 ±

0.0073 and 0.13 ± 0.0065ug/gm respectively). The results from the rats

slaughtered at 16th

day of pregnancy (24 hours post drug administration)

revealed that the liver, kidney, lung, skin, muscle (thigh and thoracic)

contained the highest concentrations (1.21 ± 0.0032, 0.84 ± 0.0085, 0.628

± 0.0061, 0.418 ± 0.0090, 0.44 ± 0.0063 and 0.39 ± 0.0070 mg/gm

respectively). Fetuses and brain contained the lowest concentrations

(0.237 ± 0.0062, 0.28 ± 0.0074 g/gm respectively). The data reported

from the rats slaughtered at 20th

day of pregnancy (5 day post drug

administration) recorded that the drug was disappeared from all tissues

except liver and kidney which contained (0.056 ± 0.0060 and 0.040 ±

0.0073 g/gm respectively)

Results …………………..………………………………………….…...

-87-

…..……………….………………..….…………………………… Results

-88-

Results …………………..………………………………………….…...

-89-

…..……………….………………..….…………………………… Results

-90-

Results …………………..………………………………………….…...

-91-

…..……………….………………..….…………………………… Results

-92-

Results …………………..………………………………………….…...

-93-

…..……………….………………..….…………………………… Results

-94-

Results …………………..………………………………………….…...

-95-

…..……………….………………..….…………………………… Results

-96-

Figure (1): Gravid rat’s uterus obtained from rat administered

therapeutic dose of enrofloxacin daily orally (10 mg/kg

b.wt) from 6th

to 15th

day of pregnancy showing early uterine

resorption.

Figure (2): Retardation of growth in a fetus obtained from rat

administered therapeutic dose of enrofloxacin daily orally

(10 mg/kg b.wt) from 6th

to 15th

day of pregnancy.

C: Control fetus T: treated fetus

Results …………………..………………………………………….…...

-97-

Figure (3): Diverticulum dilatation of brain in a fetus obtained from rat



to 15th

day of pregnancy.


Figure (4): Thymus hypoplasia in fetus obtained from rat administered


b.wt) from 6th

to 15th

day of pregnancy.


…..……………….………………..….…………………………… Results

-98-

Figure (5): Pulmonary hypoplasia with cardiac enlargement in a fetus

obtained from rat administered therapeutic dose of

enrofloxacin daily orally (10 mg/kg b.wt) from 6th

to 15th

day of pregnancy.


Figure (6): Hepatomegaly in a fetus obtained from rat administered


b.wt) from 6th

to 15th

day of pregnancy.


Results …………………..………………………………………….…...

-99-

Figure (7): Hypotrophy in left kidney in a fetus obtained from rat



to 15th

day of pregnancy.


Figure (8): Bilateral dilatation of renal pelvis in a fetus obtained from rat



to 15th

day of pregnancy.


…..……………….………………..….…………………………… Results

-100-

Figure (9): Pulmonary hypoplasia with cardiac enlargement in a fetus

obtained from rat administered double therapeutic dose of


to 15th

day of pregnancy.


Figure (10): Absence of right kidney, suprarenal gland with hypoplasia

in left kidney in a fetus obtained from rat administered

double therapeutic dose of enrofloxacin daily orally (20

mg/kg b.wt) from 6th

to 15th

day of pregnancy.


Results …………………..………………………………………….…...

-101-

Figure (11): Bilateral dilatation of renal pelvis in kidney from fetus



to 15th

day of pregnancy.


Figure (12): Absence of 4th, 5th

and 6th

sternebra with small in size of 1st,

2nd

and 3rd

in a fetus obtained from rat administered


b.wt) from 6th

to 15th

day of pregnancy.


…..……………….………………..….…………………………… Results

-102-

Figure (13): Absence of one ischum bone in a fetus obtained from rat



to 15th

day of pregnancy.


Figure (14): Absence of digit’s bone in a fetus obtained from rat



to 15th

day of pregnancy.


Results …………………..………………………………………….…...

-103-

Figure (15): Complete absence of all sternebra in fetus obtained from rat

administered double therapeutic dose of enrofloxacin daily

orally (20 mg/kg b.wt) from 6th

to 15th

day of pregnancy.


Figure (16): Complete absence of all caudal vertebrae, ischum bone,

metatarsal bone and digital bones in fetus obtained from rat

administered double therapeutic dose of enrofloxacin daily

orally (20 mg/kg b.wt) from 6th

to 15th

day of pregnancy.


…..……………….………………..….…………………………… Results

-104-

Figure (17): Lung of rat administered therapeutic dose of enrofloxacin

daily orally (10 mg/kg b.wt) from 6th

to 15th

day of

pregnancy showing thickening in wall of blood vessels of

lung due to muscular hypertrophy. H & E stain X 400.

Figure (18): Lung of rat administered therapeutic dose of enrofloxacin


to 15th

day of

pregnancy showing focal aggregation of mononuclear cell

with alveolar emphysema of lung. H & E stain X 400

Results …………………..………………………………………….…...

-105-

Figure (19): Brain of rat administered therapeutic dose of enrofloxacin


to 15th

day of

pregnancy showing odema and glaiosis. H & E stain X 400

Figure (20): Spleen from rat administered therapeutic dose of


to 15th

day of pregnancy showing lymphoid deplation with

excessive haemosiderois. H & E stain X 400

…..……………….………………..….…………………………… Results

-106-

Figure (21): Heart from rat administered therapeutic dose of


to 15th

day of pregnancy showing hyalanization of cardiac muscle.

H & E stain X 400

Figure (22): Liver from rat administered therapeutic dose of


to 15th

day of pregnancy showing extensive vacuolar of

hepatocytes. H & E stain X 400

Results …………………..………………………………………….…...

-107-

Figure (23): Kidney of rat administered double therapeutic dose of


to 15th

day of pregnancy showing perivascular lymphocytic

aggregation. H & E stain X 400

Figure (24): Uterus from rat administered double therapeutic dose of


to 15th

day of pregnancy showing odematous hyperplasia of the

chorionic villi. H & E stain X 100

…..……………….………………..….…………………………… Results

-108-

Figure (25): Uterus of rat administered double therapeutic dose of


to 15th

day of pregnancy showing desquamation in the endometerial

epithelium. H & E stain X 200

Figure (26): Placenta from rat administered double therapeutic dose of


to 15th

day of pregnancy showing calcium deposition of nectoric

area. H & E stain X 400

Results …………………..………………………………………….…...

-109-

Dia

met

er o

f In

hib

ati

on

zon

e (m

m)

Concentration of enerofloxacin (g/ml)

Fig

ure

(27):

Sta

nd

ard

cu

rve

of

enro

floxa

cin

in

ph

osp

hate

bu

ffer

pH

(7.2

) an

d n

orm

al

rat’

s se

ru

m. (n

= 1

0).

Phosp

hat

e buff

er

Norm

al r

at’s

ser

um

…..……………….………………..….…………………………… Results

-110-

Results …………………..………………………………………….…...

-111-

…..……………….………………..….…………………………… Results

-112-

4.2. Levofloxacin

4.2.1. Teratogenic effect: Pregnant female rats were given

levofloxacin intravenously injection in therapeutic dose (25 mg/kg b.wt)

and double therapeutic dose (50 mg/kg b.wt) from 6th

to 15th

day of

gestation period. Significant decrease in number of fetuses per mother

and significant decrease in the number of viable fetus were recorded.

Both doses induced a significant increase in the number of resorbed

fetuses per mother (Table 10 and figure 30). Some cases showed early

uterine resorption but other showed late uterine resorption as shown in

figure (31).

Statistical analysis of the data in table (11) revealed that

levofloxacin exerted retardation in growth of all living fetuses following

administration of both doses to pregnant rats, this results indicated that

levofloxacin in both doses retarded the growth and length of developing

fetuses during gestation period as shown in figure (32).

Visceral examination of living fetuses obtained from mother given

therapeutic dose of levofloxacin in a dose of 25 mg/kg b.wt from 6th

to

15th

day of gestation period resulted some of visceral abnormalities such

as diverticulum dilatation of the brain in 25.92%, thymus hypoplasia in

18.52%, pulmonary hypoplasia in 59.25%, cardiac enlargement in

48.14% hepatomegaly in 40.74%, kidney hypoplasia in one or both

kidney with dilatation of renal pelvis either unilateral or bilateral in

77.77% and decrease or small in size of suprarenal gland in 29.62% (table

12 and Figure 33 and 34).

Intravenous administration of double therapeutic dose of

levofloxacin (50 mg/kg b.wt) to pregnant female rat from 6th

to 15th

day

of gestation period induced diverticulum dilatation of brain in 38.89%,

Results …………………..………………………………………….…...

-113-

thymus hypoplasia in 27.67%: pulmonary hypoplasia in 83.33%, cardiac

enlargement in 66.67%, hepatomegaly of the liver in 50.00% kidney

atrophy or hypoplasia in one or both kidney with unilateral or bilateral

dilatation of renal pelvis in 94.44% and decrease or small in size of supra

renal gland in 44.44% (Table 13 and Figure 35, 36, 37, 38 and 39).

Skeletal examination of fetuses obtained from mothers given

intravenous injection of levofloxacin in therapeutic dose (25 mg/kg b.wt)

from 6th

to 15th

day of gestation period showed impaired ossification of

skull in 31.58%; absence of sternebra in 52.63% as 1st, 2

nd, 5

th, 6

th with

very small in size of 2nd

, 3rd

and 4th

. Absence of digit’s bone in fore and

hind limb in 36.84%, absence of some metatarsal bone in 21.05%, and

some metacarpal bone in 26.32%; absence of caudal vertebrae either

complete absence of caudal vertebrae, small in size of ischial bone or

presence of one bone near to vertebral column in 47.37% as shown in

table 14 and figure 40 and 41).

Administration of double therapeutic dose of levofloxacin as

intravenous injection (50 mg/kg b.wt) to pregnant female rats from 6th

to

15th

day of gestation period resulted in impaired ossification of skull in

45.45%; absence of sternebra in 72.73%. Some cases showed small in

size of 1st, 2

nd, 5

th and 6

th with broken of 4

th and 5

th but other cases

showed presence of small dispersed bone with absence of other sternebra.

Absence of digital bones of fore and hind limb in 63.64%; absence of

some metatarsal bone in 54.55% and some metacarpal bone in 63.64%

complete absence of caudal vertebrae with ischial bone either absence or

small in size in 81.82% of examined fetuses as shown in table (15) and

figure (42 and 43).

…..……………….………………..….…………………………… Results

-114-

4.2.2. Histopathological examination:

Histopathological examination of brain, lung, liver, kidney, spleen,

intestine, heart, uterus and placenta of the pregnant female rats

administered therapeutic dose of levofloxacin (25 mg/b.wt) intravenously

from 6th

to 15th

day of pregnancy revealed some pathologic lesions in

mothers. The liver showed hydropic degeneration in hepatocytes with

infiltration of liver by inflammatory cell mainly lymphocytes, while

kidney showed necrosis (Figures 44 & 45), focal proliferation of glial cell

of brain with cerebral and cerebllum encephalomalesia (Figures 46, 47 &

48). The spleen showed lymphocyic deplation with haemosiderosis,

catharhal enteritis was also detected in the intestine.

Double therapeutic dose of levofloxacin (50 mg/kg b.wt) resulted

in many histopathological changes as prevascular lymphocytic

aggregation of the lung (Figure 49); degeneration of renal tubules with

lymphocytic aggregation of the kidney (Figure 50); hydropic

degeneration of the hepatocyte (Figure 51) and loss of striation of cardiac

muscle fibers with lymphocytic aggregation of the heart (figure 52). The

histopathological changes in the uterus and placenta mainly occur with

double therapeutic dose. Uterus revealed congestion of blood vessels with

lymphocytic infiltration in the lamina propria and submucosa but other

cases reported congestion of blood vessels, presence of patches of

lymphocytic infiltration in the proprea and around arterioles with

presence area of necrosis. Placenta revealed congestion of blood vessels

of surface of placenta with cellular desquamation in lining epithelium but

other cases showed area of necrosis in the villus surface (Figures 53, 54,

and 55).

Results …………………..………………………………………….…...

-115-

4.2.3. Standard curves of levofloxacin:

Concentration of 0.025, 0.05, 0.1, 1, 1.25 (reference concentration)

1, 2.5, 5, 10 mg of levofloxacin per milliliter phosphate buffer (pH 6.7) or

normal rat’s serum as well as their corresponding zone of inhibition were

illustrated in table (16) and show in Figure (56).

4.2.4. Serum and tissue concentrations of levofloxacin:

Following intravenous injection of therapeutic and double

therapeutic dose of levofloxacin once daily. Serum and tissue

concentrations of therapeutic dose of levofloxacin following (25 mg/kg

b.wt) once daily were represented in table (17) and show in Figure (57).

The data revealed distribution of the drug in tested tissues (brain, lung,

heart, liver, spleen, kidney, thigh and thoracic muscle, fat, skin and whole

fetuses). The data revealed that liver, kidney contained the highest drug

concentrations (0.41 ± 0.0043 and 0.45 ± 0.0061 g/gm respectively in

rats slaughtered at 10th

day of pregnancy. On other hand, the lowest

concentrations was recorded in brain, spleen, heart and whole fetuses

(0.11 ± 0.0043, 0.10 ± 0.0037, 0.12 ± 0.0029 and 0.126 ± 0.0048 g/gm

respectively). The data reported from rats slaughtered at 16th

day of

pregnancy (24 hours after last dose administration resulted in highest

concentrations of drug in liver, kidney, lung and skin (0.80 ± 0.0087, 0.87

± 0.0058, 0.63 ± 0.0049 and 0.46 ± 0.0049 g/gm respectively). The

whole fetus and spleen contained the lowest concentration of levofloxacin

(0.202 ± 0.0042 and 0.22 ± 0.0108 g/gm respectively). The data resulted

from the rats slaughtered at 20th

day of pregnancy (5 days post drug

administration, the drug can not be assayed in all tissues except liver and

kidney which contained low concentrations (0.022 ± 0.0092 and 0.028 ±

0.0092) g/gm respectively as shown in table (17) and Figure (58).

…..……………….………………..….…………………………… Results

-116-

The serum and tissue concentrations following administration of

double therapeutic dose of levofloxacin (50 mg/kg b.wt ) were recorded

in table (18) and figure (58). The data revealed that the highest

concentration of the drug after double therapeutic administration in liver,

kidney, lung of slaughtered rats at 10th

day of pregnancy (0.55 ± 0.0053,

0.65 ± 0.0040 and 0.42 ± 0.0074 g/gm respectively). Fetuses, heart and

spleen contained the lowest concentrations (0.183 ± 0.0029, 0.178 ±

0.0036 and 0.14 ± 0.0034 g/gm respectively). The results from the rats

slaughtered at 16th

day of pregnancy (24 hours post drug administration)

revealed that the liver, kidney, lung, skin contained, the highest

concentrations (0.91 ± 0.0138, 1.38 ± 0.0270, 0.73 ± 0.0049 and 0.608 ±

0.0141 g/gm respectively). Fetuses, heart and spleen contained the

lowest concentrations (0.247 ± 0.0060, 0.30 ± 0.0052 and 0.34 ± 0.0819

g/gm respectively). The data reported from the rats slaughtered at 20th

day of pregnancy (5 days post drug administration indicated that the drug

disappeared from all tissues except liver, kidney and lung (0.020 ±

0.0047, 0.036 ± 0.0071 and 0.046 ± 0.0060 g/gm respectively).

Results …………………..………………………………………….…...

-117-

…..……………….………………..….…………………………… Results

-118-

Results …………………..………………………………………….…...

-119-

…..……………….………………..….…………………………… Results

-120-

Results …………………..………………………………………….…...

-121-

…..……………….………………..….…………………………… Results

-122-

Results …………………..………………………………………….…...

-123-

…..……………….………………..….…………………………… Results

-124-

Results …………………..………………………………………….…...

-125-

…..……………….………………..….…………………………… Results

-126-

Figure (30): Gravid rat’s uterus in a fetus obtained from rat administered

therapeutic dose of levofloxacin daily intravenously (25


to 15th

day of pregnancy.

Figure (31): Gravid rat’s uterus in a fetus obtained from rat administered

double therapeutic dose of levofloxacin daily intravenously


to 15th

day of pregnancy, it showed

late resorbed fetuses.

Results …………………..………………………………………….…...

-127-

Figure (32): Retardation of growth in a fetus obtained from rat

administered double therapeutic dose of levofloxacin daily

intravenously (50 mg/kg b.wt) from 6th

to 15th

day of

pregnancy.


Figure (33): Diverticulum dilatation of the brain in a fetus obtained from

rat administered therapeutic dose of levofloxacin daily


to 15th

day of

pregnancy.


…..……………….………………..….…………………………… Results

-128-

Figure (34): Bilateral dilatation of renal pelvis in a fetus obtained from

rat administered therapeutic dose of levofloxacin daily


to 15th

day of

pregnancy.


Figure (35): Absence of thymus gland in a fetus obtained from rat



to 15th

day of

pregnancy.


Results …………………..………………………………………….…...

-129-

Figure (36): Pulmonary hypoplasia with cardiac enlargment in a fetus


levofloxacin daily intravenously (50 mg/kg b.wt) from 6th

to

15th

day of pregnancy.


Figure (37): Hepatomegaly in a fetus obtained from rat administered

double therapeutic dose of levofloxacin daily intravenously


to 15th

day of pregnancy.


…..……………….………………..….…………………………… Results

-130-

Figure (38): Hypoplasia in both kidney with small in size of suprarenal

gland in a fetus obtained from rat administered double



to 15th

day of pregnancy.


Figure (39): Atrophy in right kidney with small in size of suprarenal

gland in a fetus obtained from rat administered double



to 15th

day of pregnancy.


Results …………………..………………………………………….…...

-131-

Figure (40): Impaired ossification of skull in a fetus obtained from rat

administered therapeutic dose of levofloxacin daily


to 15th

day of

pregnancy.


Figure (41): Absence of digit’s bone in a fetus obtained from rat

administered therapeutic dose of levofloxacin daily


to 15th

day of

pregnancy.


…..……………….………………..….…………………………… Results

-132-

Figure (42): Presence of small scattered three bone of strenbrae in a fetus



to

15th

day of pregnancy.


Figure (43): Absence of one ischum bone and appear small in size and

near to the vertebral column in a fetus obtained from rat



to 15th

day of

pregnancy.


Results …………………..………………………………………….…...

-133-

Figure (44): Liver of rat administered therapeutic dose of levofloxacin

daily intravenously (25 mg/kg b.wt) from 6th

to 15th

day of

pregnancy showing hydropic degeneration of hepatocytes.

H & E stain X 200

Figure (45): Kidney of rats administered therapeutic dose of levofloxacin


to 15th

day of

pregnancy showing coagulative necrosis of renal tubules.

H & E stain X 100.

…..……………….………………..….…………………………… Results

-134-

Figure (46): Brain of rats administered therapeutic dose of levofloxacin


to 15th

day of

pregnancy showing focal proliferation of glial cells. H & E

stain X 200.



to 15th

day of

pregnancy showing encephalomalecia of the cerebllum. H &

E stain X 400

Results …………………..………………………………………….…...

-135-



to 15th

day of

pregnancy showing cerebral encephalomalacia. H & E stain

X 400.

Figure (49): Lung of rats administered double therapeutic dose of


to

15th

day of pregnancy showing perivascular lymphocytic

cellular aggregation and alveolar emphysema. H & E stain X

200.

…..……………….………………..….…………………………… Results

-136-

Figure (50): Kidney of rats administered double therapeutic dose of


to

15th

day of pregnancy showing degeneration of the renal

tubuls and focal lymphocytic cellular aggregation. H & E

stain X 200.

Figure (51): Liver of rats administered double therapeutic dose of


to

15th

day of pregnancy showing extensive hydropic

degeneration of hepatocytes. H & E stain X 200.

Results …………………..………………………………………….…...

-137-

Figure (52): Heart of rats administered double therapeutic dose of


to

15th

day of pregnancy showing hyalinization of some cardiac

muscles with aggregation of few lymphocytes. H & E stain

X 200.

Figure (53): Uterus of rats administered double therapeutic dose of


to

15th

day of pregnancy showing congested blood vessels,

focal lymphocytic cellular infiltration and necrosis. H & E

stain X 200.

…..……………….………………..….…………………………… Results

-138-

Figure (54): Placenta of rats administered double therapeutic dose of

levofloxacin daily intravenously (50mg/kg b.wt) from 6th

to

15th

day of pregnancy showing oedema and congestion of the

blood vessels. H & E stain X 200.

Figure (55): Placenta of rat administered double therapeutic dose of

levofloxacin daily intravenously (50mg/kg b.wt) from 6th

to

15th

day of pregnancy showing desquamation of the lining

epithelium with presence of necrosis in villus. H & E stain X

100.

Results …………………..………………………………………….…...

-139-

Dia

met

er o

f In

hib

ati

on

zon

e (m

m)

Fig

ure

(5

6):

Sta

nd

ard

curv

e of

lev

ofl

ox

acin

in

ph

osp

hat

e bu

ffer

pH

(6

.7)

and

no

rmal

rats

ser

um

. (n

= 1

0).

Concentration of levofloxacin (g/ml)

P

hosp

hat

e buff

er

Norm

al r

at’s

ser

um

…..……………….………………..….…………………………… Results

-140-

Results …………………..………………………………………….…...

-141-

Documents

4. RESULTS - bu.edu.eg · The preceptation of calcium salt (mineralization) in placenta was also reported as shown in figure (26). 4.1.3. Standard curves of enrofloxacin: