الفهرس 
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Abstract
Mohamed, Khaled Gamal El-Deen
Protective Effect of a Natural Herb (Rosmarinus officinalis)
Against Hepatotoxicity in Male Albino Rats
Ph.D., Fac. of Sc., Ain Sahms Univ., Cairo, 2009.
Key Words: Rosemary extracts, hepatotoxicity, carbon tetrachloride, liver, albino rats and paraoxonase1 (PON1).
Rosemary extracts are widely used in the food, nutraceutical and cosmetic areas. Their major bioactive components have shown antioxidant, antimicrobial, anti-inflammatory, antitumorigenic, chemopreventive and radical scavenging activities. The present study was designed to study both the protective and curative effects of orally-administrated aqueous extract of rosemary at either low (220 mg/kg/day b.w) and high (440 mg/kg/day b.w) doses against CCl4-induced hepatotoxicity (1ml/kg twice/week) and to evaluate the possible use of serum paraoxonase activity alone or in combination with standard liver function tests in assessment of the degree of liver damage and discrimination between intoxicated and normal subjects.
This was monitored by biochemical measurements (in both serum and liver homogenate), protein electrophoresis of the serum and histopathological examination of liver tissue.
The obtained results revealed that single extract dose up to 4.5 g/kg b.w did not show any mortality or toxicity symptoms within the first 72 hours, moreover, 440 mg/kg/day for eight weeks did not induce any metabolic disorders, especially liver functions, therefore, reflected its safety at this dose levels and duration. Also, the obtained results showed that rosemary extract inhibited and modulated, in a dose and duration-dependant manner, the induced CCl4 hepatotoxicity effects, this was monitored from the decreased activities of serum ASAT, ALAT, GGT and ALP; decreased levels of bilirubin, triglycerides, total cholesterol, and LDL-c as well as hepatic MDA level and area of fibrosis. On the other hand, it increased serum levels of total proteins, albumin, A/G ratio, HDL-c and HDL-c/LDL-c ratio and hepatic glutathione reductase activity.
In additin, the extract remitted the altered protein banding pattern by reappearance of the missed bands and elimination of the newly formed ones; this besides to modulation of the changed band amount towards normal ones. Moreover, the histological examination showed that the extract, prevented in a dose and duration-dependant manner, CCl4-induced inflammation, necrosis, vacuolation and fibrosis. These modulatory effects of rosemary could be attributed to the bioactive constituents those alleviated the deleterious effect of CCl4 either by the well-known scavenging action or the antioxidant properties that inhibited lipid peroxidation, stabilized the reactive radicals, preserve the cellular integrity and restrain the severity of CCl4.
Also the obtained data declared that serum PON1 activity revealed a negative correlation with area of fibrosis; serum ASAT, ALAT, GGT & ALP activities; serum total cholesterol and LDL-c levels and hepatic MDA level; and a positive correlation with serum total proteins and HDL-c levels and hepatic GR activity.
In conclusion, aqueous extract of rosemary may be exerted preventive and curative effects against CCl4-induced hepatotoxicity. The measurement of serum PON1 activity could be added to the battery of the biochemical liver function, to assess the degree of liver damage and to discriminate between intoxicated and normal subjects.