الفهرس 
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Abstract
This study aimed to study the clinicopathological and histopathological studies of Doxycycline toxicity in rats. Therefore, the experiment was carried out on forty, 3-month-old male albino rats of 170-200 gm body weight. They were housed in four metal cages (10 rats each). Rats were given commercial basal diet, water and milk adlibitum. All animals were housed under the recommended environmental conditions up to two weeks before experiment for adaptation and to ensure normal growth and behavior.
Rats were randomly divided into four equal groups (10 rats of each) as in the following: group 1: Control group (did not receive any treatment), group 2: (Received doxycycline hyclate 5 mg/Kg intragastrically twice daily (8 am and 8 pm) which is standard dose), group 3: (Received doxycycline hyclate 25 mg/Kg intragastrically twice daily (8 am and 8 pm) which is 5-fold higher than the standard dose), group 4: (Received doxycycline hyclate 50 mg/Kg intragastrically twice daily (8 am and 8 pm) which is 10-fold higher than the standard dose)
Hematological examination
Doxycycline treatments cause significant elevation in RBCs count and Hb concentration count in group 2 and 3 compared to control after two weeks of treatment, while after four weeks of doxycycline treatment, RBCs count and Hb concentration was significantly elevated in group 2 compared to control group. Doxycycline treatment caused significant increase in HCT% in group 2 after two and four weeks of treatment. Doxycycline treatments caused significant decrease in MCV values in groups 2 and 3 after two weeks of doxycycline treatment compared with control group while After four weeks of doxycycline treatment, MCV values were significantly increased group 3 and 4 compared with control group.
Doxycycline treatments caused significant increase in MCH (pg) in group 4 during both point of treatment. Doxycycline treatments caused significant increase in MCHC % in all treated group compared to control group after two weeks of treatment while after four weeks of treatment caused non-significant change in MCHC % values compared to control group.
Doxycycline treatments caused significant decrease in WBCs count in group 3 during first two weeks compared to control one. However, after 4 weeks of treatment there was a significant increase in WBCs count in group 2 rats compared to control group. Doxycycline treatments induced significant increase in neutrophils in all treated groups compared to control group after two weeks and in groups 2,3 after four weeks of treatment. Doxycycline treatments caused significant reduction in lymphocyte in all treated groups after two weeks of treatment and in group 2 and 3 after four weeks of treatment compared to control group. Doxycycline treatments induced significant increase in monocyte % in group 2 and 3 after two weeks, group 3 after four weeks of treatment when compared with control group. While there was a significant decrease in group 4 after two and four weeks of treatment. Doxycycline treatment induced a significant increase in eosinophils % in group 3 and 4 after both two and four weeks of treatment compared to control group. Basophils did not record any changes either after 2 or four weeks of experiments.
There was significant reduction in platelets count in all treated groups compared to control group at two time points of the experiments.
Biochemical results:
There was significant elevation in serum activity of ALT, AST, ALP, and SGGT level in groups 2, 3 and 4 after both two and four weeks of treatment in compared with control group. Doxycycline treatments induced significant increase
in serum total protein, albumin, globulin level during both two and four-weeks post treatment compared to control group.
Doxycycline treatment caused significant reduction on the level of serum urea and creatinine in all treated group after two weeks post-treatment when compared to control group. On the contrary, after four weeks post-treatment, significant elevated serum urea and creatinine level in all the treated groups compared to control group were observed.
Doxycycline treatments caused significant increase in level of LDH, CKMB, Troponin-1 in all treated groups after two and four weeks of treatment with doxycycline when compared to control group.
Doxycycline treatments caused significant increase in the level of MDA in hepatic, renal and cardiac tissue in all the treated groups when compared to control group after four weeks of treatment.
Doxycycline treatments caused significant decrease of GSH in hepatic, renal and cardiac tissues in all four groups after four weeks of treatment.
Histopathological findings:
Liver:
Two weeks posts treatment of doxycycline: liver showed moderate cytoplasmic vacuolation of the hepatocytes, Periportal and mid-zonal hepatic necrosis with mononuclear cells infiltration in group (2); group (3) liver showed cytoplasmic vacuolation of lipid type, multifocal areas of hepatic necrosis which were infiltrated with inflammatory cells, moderate thickening of the portal triads by
mononuclear cell infiltrates; in group (4) the hepatic parenchyma exhibited severe congestion associated with focal hemorrhages. The hepatocytes showed cytoplasmic vacuolation besides widespread focal area of hepatic necrosis with intense mononuclear cell infiltration. Moreover, the portal areas were expanded by congested blood vessels, mononuclear cells, and fibroplasias. Four weeks posts treatment of doxycycline: the hepatocytes showed diffuse cytoplasmic vacuolation, besides multifocal areas of necrosis with mononuclear cell infiltration were still present. Also, widespread hemorrhages and severe vascular congestion were noticed. Furthermore, there was extensive brooding of the portal areas with obvious connective tissue proliferation as well as intense mononuclear cell aggregation.
Kidney:
Two weeks posts treatment of doxycycline: kidney showed tubular lumen rendering the lumen narrow and star-shaped, vascular congestion, Interstitial nephritis with moderate inflammatory cells infiltration in group (2); group (3) kidney showed vascular congestion, degeneration and necrosis of renal lining epithelium, multifocal interstitial nephritis characterized by interstitial lym lymphocytic infiltrates associated with interstitial fibrosis, Also, necrotic glomeruli with presence of necrotic remnant of capillary tufts; group (4) kidney showed interstitial nephritis with moderate inflammatory cells infiltrations was evident in the renal cortex. There was vascular congestion and slight fibroplasias. Four weeks post- treatment with doxycycline: the abovementioned renal lesions were still present, and they were increased in the severity and the distribution. Additionally, few glomeruli showed formation of epithelial crescent in the Bowman’s space.
Heart:
Two weeks posts treatment of doxycycline: heart showed Myocardial degeneration, Individual muscle fibers exhibited Zenker’s degeneration
characterized by loss of their striations with homogenous hypereosinophilic sarcoplasm and pyknoyic nuclei, multifocal areas of myocardial necrosis infiltrated with mononuclear cells; Furthermore, congestion of the interstitial blood vessels and interfibrillar hemorrhage in group (2); group (3) heart showed the myocardial fibers showed vacuolation besides vascular congestion and flocculation, in addition, perivascular mononuclear cells infiltration, while in group (4) recorded lesions were the same as previously mentioned in the previous two groups with increased severity and the distribution. The degenerative lesions in the form of fragmentation and flocculation, Mononuclear cells were diffusely infiltrated in the interstitium. Focal myocardial necrosis infiltrated with mononuclear cells. Four weeks post-treatment with doxycycline, the abovementioned cardiac lesions were still present, and they were increased in the severity and the distribution. The degenerative lesions in the form of vacuolation and flocculation were marked, multifocal areas of interstitial hemorrhages were noticed.