الفهرس 
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Abstract
The current study aimed to investigate the potential protective effect of geraniol (GOH) against cyclophosphamide (CP)-induced hepatotoxicity in rats and to investigate the underlying molecular mechanisms by the assessment of different hepatotoxicity indices, oxidative/nitrosative stress markers and inflammatory and immune markers. as well as the modulatory effect of geraniol on PPAR- γ and MAPK signaling pathways.
The main findings of the present study are summarized as follows:
36 rats were randomly divided into five groups 6 rats each.
First group, served as control; received corn oil (0.25 ml/100g, p.o.), and normal saline (1 ml/kg, i.p.), once daily for 10 days.
Second group received corn oil (0.25 ml/100g, p.o.) 1 hour before administering CP (25 mg/kg, i.p.) dissolved in normal saline, once daily for 10 days.
Third and fourth groups received GOH (100 and 200 mg/kg body weight, p.o., respectively) dissolved in corn oil, 1 hour before administering CP (25 mg/kg i.p.), once daily for 10 days.
Fifth group received GOH (200 mg/kg body weight), followed by normal saline (1 ml/kg, i.p.) 1 hour later, once daily for 10 days.
Assessed parameters:
Hepatotoxicity markers: Alanine aminotransferase (ALT), Aspartate aminotransferase (AST) and Alkaline phosphatase (ALP).
Inflammatory markers: Cycloxygenase-2 (COX-2), interleukin-1beta (IL-1β), inducible nitric oxide synthase (iNOS), nuclear factor-kappa B (NF-KB-p65), peroxisome proliferator-activated receptor gamma (PPAR-𝛾), P38 mitogen-activated protein kinases, Phospho JNK and Tumor Necrosis Factor (TNF-α).
Oxidative/Nitrosative stress markers: Reduced glutathione (GSH), thiobarbituric acid reactive species (TBARS) and nitric oxide (NO).
Histological Examination
The main findings of the current study are summarized as follows:
1. Geraniol at doses (100 and 200 mg/kg) was proven to reduce ALT, AST and ALP levels indicating its ability to reverse Cyclophosphamide -induced hepatotoxicity.
2. Geraniol significantly counteracted the oxidative/nitrosative stress damage induced by Cyclophosphamide by raising the level of GSH and decreasing NO and MDA.
3. Geraniol exhibited anti-inflammatory effects via the significant decrease in the expression of COX-2, iNOS and NF-KB-p65 as well as the levels of TNF-α and IL-1β.
4. Western blot analysis showed that Geraniol administration increased PPAR-γ and decreased p38-MAPK and JNK activation without any change in the total protein content of these kinases.
5. Administration of Geraniol ameliorated all pathological alterations as evidenced by normal hepatic lobules with widening of central vein, slight portal fibrosis and inflammation with a few bile ductules formation and congested blood vessels. Moreover, binucleated hepatocytes were observed in Geraniol treated rats, indicating liver regeneration.