الفهرس 
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Abstract
7. The aim of the present study is to clarify the effect of rosemary extract administration against paracetamol and aspartame overdose-induced damage in rats. For performing the present work, adult male albino rats (120-140 g) were used. Animals were divided into five groups designed as the following:
Group (1): was regarded as control group: received distilled water.
Group (2): administered paracetamol at dose level of 1000 mg/kg b.wt for two months.
Group (3): (administered rosemary & paracetamol ) was given rosemary extract at dose level of 125 mg/kg b.wt and paracetamol 1000 mg/kg b.wt for two months.
Group (4): administered aspartame at dose level of 1000 mg/kg b.wt for three months.
Group (5): (administered rosemary & aspartame ) was given rosemary extract at dose level of 125 mg/kg b.w and aspartame 1000 mg/kg b.wt for three months.
All the treatments were performed orally and one time per two days.
By the end of the experimental periods all groups were sacrificed. liver, kidney and testes were rapidly removed from each animal for:
1- Studing the histopathological change.
2- Determination of oxidative stress (lipid peroxidation) and antioxidant defense system: glutathione content (GSH) and activities of glutathione-S-transferase (GST), glutathione peroxidase (GPX) and superoxide dismutase (SOD).
Blood samples were collected from each rat for the following:
1- Determination of serum aminotransferases (AST and ALT), alkaline phosphatase (ALP), -glutamyl transferase (GGT), lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) activities.
2- Determination of serum total protein, albumin and globulin levels.
3- Determination of serum levels of urea, creatinine and uric acid.
4- Determination of serum levels of sodium, potassium, -fetoprotein (AFP) and tumor necrosis factor (TNF).
5- Determination of serum levels of sex steroid hormones (FSH, LH and testosterone).
The obtained data were subjected for statistical analysis and revealed the following:
1) Paracetamol induced a highly significant increase in serum activities of all measured enzymes. Aspartame also increased significantly serum AST, ALP and LDH activities. Treatment with rosemary extract reduced the elevated enzymes activities.
2) Paracetamol decreased the levels of total protein and albumin in serum. Aspartame reduced the serum albumin levels while raised the globulin levels. Treatment with rosemary extract retained the normal levels of albumin and total protein.
3) Both paracetamol and aspartame increased the levels of urea, creatinine, uric acid, potassium, AFP and TNF in serum while reduced the levels of sodium. The presence of rosemary extract ameliorate these effects but AFP showed non significant change.
4) With regards to sex steroid hormones, they were commonly decreased in both paracetamol and aspartame groups. The treatment with rosemary extract produced a non significant change in serum FSH, LH and testosterone levels.
5) Regarding to the oxidative stress and antioxidant defense system, lipid peroxidation in liver, kidney and testis were profoundly elevated in paracetamol and aspartame groups. However, the changes of glutathione contents and endogenous antioxidative enzymes in liver, kidney and testis of paracetamol administered animals were decreased. Aspartame caused significant decrease in glutathione content (in kidney and testis) and activities of antioxidative enzymes in liver, kidney and testis, but GST in testis showed non significant change. The presence of rosemary extract attenuated the oxidative stress induced by paracetamol or aspartame by decreasing lipid peroxidation levels, elevated antioxidant enzyme activity and replinshed GSH content in liver, kidney and testis.
6) Paracetamol and aspartame overdoses produce alterations in histopathology in liver, kidney and testis. The treatment with rosemary extract improve the structural integrity of the liver and kidney.
In conclusion, the present study provides evidence that both paracetamol and aspartame overdoses result in many adverse effects and concomitant administration of rosemary with paracetamol or aspartame can mitigate these effects. However, further clinical studies are required to assess the safety and efficacy of rosemary in human beings.