الفهرس 
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Abstract
The present study aims to explore the possible protective effects of both the ethanolic extract of R. graveolens and its active constituent rutin against DEN-induced hepatocarcinogenesis and renal injury. Rats received a single intraperitoneal dose (200 mg / Kg.bwt) of DEN. Two weeks after administration, rats received 0.5g /L of phenobarbital in drinking water for 12 weeks. R.graveolens extract and rutin (50 mg/ kg b.wt) were orally administered from the first day of the experiment. Then we investigated the biochemical and histological changes.
For testing the effect of both the extract and its active constituent, male albino rats were divided into four groups (6 rats / each) designated as follow:
group I (control): animals were injected with a single dose of saline (0.9%) and orally administered the vehicle 1% carboxymethylcellulose (CMC).
group II (DEN): animals were given a single intraperitoneal injection of DEN (200 mg /kg b.wt) dissolved in saline and given 1% CMC by gavage daily throughout the experimental period. Two-weeks after DEN administration, rats received 0.5g/L phenobarbital in drinking water for 12 weeks.
group III (DEN + R. graveolens): DEN/PB-treated animals received (50mg/kg b.wt) R. graveolens dissolved in 1% CMC by gavage daily throughout the experimental period.
group IV (DEN+rutin): DEN/PB-treated animals received (50 mg /kg b.wt) rutin by gavage daily throughout the experimental period.
At the end of the experimental period, the animals of all groups were sacrificed under mild diethyl ether anesthesia and blood samples and tissues were collected. The clear non haemolysed supernatant serum was quickly removed for analysis of various biochemical parameters. While, fixed tissue specimens of liver and kidney were examined for the histological lesions demonstration. Another part of the selected tissues was homogenized in 0.9% NaCl (10% w/v) for the measurement of oxidative stress markers.
The obtained data of the above mentioned investigations can be summarized in the following:
In liver, contentious treatment of DEN-administered rats with both R.graveolens ethanolic extract and its active constituent phenolic compound, rutin caused a significant decrease in the activity of all liver enzymes ALT, AST, γGT, LDH, ALP and total bilirubin and significantly ameliorated the decreased level of albumin. Also, both the extract and the chemical compound showed a significant decrease in the elevated level of lipid peroxidation and alleviated the content of GSH and the activity of SOD, Gpx and GST. The severity of the liver histological lesions noticed after DEN injection was greatly ameliorated after the daily administration of either Ruta extract or rutin. However: rutin showed nearly normal structure of liver.
In kidney, concurrent treatment of DEN-administered rats with either R. graveolens extract as well as its active component rutin revealed a marked amelioration in the elevated concentrations of urea, creatinine and uric acid. Both treatments prevented the elevation of lipid peroxidation to a great extent and lead to a potent amelioration of the reduced renal content of GSH and improved the activity of SOD, Gpx and GST. The most noticed renal histological lesions resulted from DEN administration was nearly disappeared after the daily administration of either Ruta extract or rutin.
Concerning to AFP, TNF-α and adiponectin, the increased levels of both AFP and TNF-α in DEN-administered rats were decreased due to contentious treatment with Ruta and rutin. While the decreased level of adiponectin in DEN-administered was ameliorated because of the daily administration of Ruta extract and rutin.
In Conclusion:
Data of the current study indicate that R. graveolens and its active constituent rutin exert protection against DEN-initiated/PB-promoted hepatocarcinogenesis and renal toxicity in albino rats. This hepatorenal protection could be attributed to attenuation of the pro-inflammatory cytokine production, and inhibition of the lipid peroxidative system through prevention of GSH depletion and enhancement of the enzymatic antioxidants. In addition, increased serum level of adiponectin seems to be involved in the anti-inflammatory effect of both R. graveolens and rutin.