الفهرس 
Kidney anatomy and physiologyOnly 14 pages are availabe for public view
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Abstract
The current study was carried out on adult male albino rats to
examine the possible beneficial effect of L-carnitine low and high dose
in preventing the acute renal failure and related oxidative stress caused
by administration of gentamicin in rats and to examine the effects of Lcarnitine doses on the haematological and biochemical changes results
from nephrotoxicityof gentamicin.
The animals were classified into two main groups:
Group 1: Normal control group injected with saline (21 rats).
Group 2: Comprises rats (nephrotoxic group) (49 rats) injected
intraperitoneal with gentamicin (80 mg/ kg / day) for 10
days.
After 10 days 7 rats from each group were sacrificed and blood
samples were collected then divided into four blood samples for
estimation of biochemical and haematological parameters. A clean dry
test tube 1 for serum to estimate β2- microglobuline, urea, creatinine,
total protein, albumin, globulin level, Sodium (Na) and Potassium (K),
total antioxidant status (TAS), total oxidative status (TOS), oxidative
stress index (OSI), total nitric oxide (TNO), ferritin, transferrin,
Iron(Fe), total iron binding capacity (TIBC) and transferrin
saturation%, tube2 containing EDTA blood for estimation of complete
blood count (CBC), tube3 containing heparinized blood for
determination of osmotic fragility and tube4 containing plasma sodium
citrate was used for prothrombin time (PT), partial prothrombin time
(APTT) and fibrinogen levels.
Then the remaining of normal control animal rats was served as
normal control rats group (Group 1) (14 rats), while the remaining 42
nephrotoxic rats will further subdivided in to the following subgroups:
Subgroup2– (Control 2) nephrotoxic rats (14 rats).
Subgroup3– Nephrotoxic rats injected intraperitoneal with low dose
of L-carnitine (300 mg/kg/day) (14 rats) for 15and 30 days.
Subgroup4– Nephrotoxic rats injected intraperitoneal with high dose
of L-carnitine (600 mg/kg/day) (14 rats) for 15and 30 days. At the end of each periodof experiment, 7 rats from each above
group were sacrificed and measurement criteria mentioned above
after15 days and 30 days.
Gentamicin induced a significant increase in the serum levels of
β2- microglobulin, urea, creatinine and potassium (K). In addition,
significant increase in serum level of globulin was noticed. In contrast
a significant decrease in the serum levels of total protein, albumin and
sodium (Na) were detected in nephrotoxic rats group compared to
normal control rats group.
A marked decrease was observed in serum β2-microglobulin,
urea and creatinine after rats were treated with L-carnitine as compared
to nephrotoxic rats group and increase occurred in total protein and
albumin levels, but globulin level decreased. Marked decrease
occurred in serum k and marked increase occurred in serum Na.
Gentamicin induced amarked decreasewas observed in total
nitric oxide (TNO) contents and in total antioxidant status (TAS) in
nephrotoxic group as compared to its corresponding values in the
normal control group. However, a marked increase for total oxidant
status (TOS) and oxidative stress index (OSI), was observed in
nephrotoxic group compared to normal control.
Increase was observed in serum TNO and TAS after rats were
treated with L-carnitine as compared to nephrotoxic rats group.
Additionally, the supplementation of L-carnitine to nephrotoxic rats
group led to a significant decrease in the serum of TOS and OSI.
Gentamicin clarified a significant decreasein red blood cells
(RBCs), haemoglobin (Hb) concentrations, hematocrit (Hct), white
blood cells (WBCs), granulocyte concentration and platelets count in
nephrotoxic rats group. Elevation in the concentration of monocyte
was reported in nephrotoxic rats group. While, a numerical change but
not significant was observed in the levels of mean corpuscular volume
(MCV), mean corpuscular haemoglobin (MCH), mean corpuscular
haemoglobin concentration (MCHC) and lymphocyte concentration in
nephrotoxic rats group compared to their corresponding normal control
ratsThe supplementation of L-carnitine to nephrotoxic rats group
led to a significant increase in the concentration of RBCs, Hb and Hct.
Insignificant correlation detected between dose of L-carnitine and
blood levels of MCV, MCH and MCHC.Moreover, a marked increase
occurred in the concentration of WBCs and platelets count in
nephrotoxic rats group were treated with low and high dose of Lcarnitine. Decrease in the level ofmonocyte concentration and
significantincrease in level of granulocyte concentration, no
remarkable changes were noted in the level of lymphocyte
concentration during the study period.
Gentamicin treatment induced a high significant increase in
prothrombin time (PT) and activated partial thromboplastin time
(APTT) as compared to normal control group and fibrinogenelevated
compared to their corresponding normal control rats
A significant decrease occurred in the levels of PT, APTT and
fibrinogen after rats were treated with L-carnitine in relation to
nephrotoxic rats group.
Gentamicin treatment induced a high significant increase in
osmotic fragility level. A marked decrease occurred in osmotic
fragility initial and complete after rats were treated with L-carnitine as
compared to nephrotoxic rats group.
Gentamicin treatment clarified a significant increase in ferritin,
iron (Fe), total iron binding capacity (TIBC) and transferrin. While, a
numerical change but not significant was observed in the percentage of
transferrin saturation in nephrotoxic rats group compared to their
corresponding normal controlrats.
The supplementation of L-carnitine to nephrotoxic rats group
led to a significant decrease in the serum Fe, TIBC, ferritin and
transferrin. No remarkable changes were reported for transferrin
saturation before and after treated with L-carnitine through the
experimental duration compared to nephrotoxic rats group.
Accordingly, from the above results it was noticed that in all
parameters under investigation the maximum improvement was
noticed in the last intervals (30 days) after the rats were treated with high dose of L-carnitine (600 mg/kg b.wt.) and this indicated that
improvement in this study dependind on time and concentration of
dose of L-carnitine. Thus, the current investigation was designed to
examine the possible beneficial effect of L-carnitine in preventing the
acute renal failure and related oxidative stress caused by administration
of gentamicin in rats and L-carnitine led to a significant amelioration
effects on the haematological and biochemical changes results from
nephrotoxicity of gentamicin.
In conclusion, this study demonstrated that L-carnitine through
its marked antioxidant activity coupled with favorable hemodynamic
effects salvages gentamicin nephrotoxicity and oxidative stress
depending on the dose and time of treatment. So, this study
recommends that gentamicin therapy should be preceded and followed
up by renal function tests must be done to detect any early functional
dearangement. Treatment with 600 mg/kg b.wt. L-carnitine for 30 days
proved to have a better protective action against gentamicin
nephrotoxicity than 300 mg L-carnitine. Therefore, 600mg L-carnitine
might open a new therapeutic possibility in patients with impaired
renal function.