الفهرس 
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Abstract
Aim:
To evaluate the protective effect of hesperidin, naringin and their mixture against diclofenac-induced liver, kidney and heart toxicities.
Material and method:
Thirty adult male albino rats were divided into five groups of 6 animals. Normal control group A received the appropriate volume of saline intraperitoneally (i.p). Diclofenac sodium (3 mg/kg. b. wt ) treated group B for 4 weeks. group C was given diclofenac sodium plus naringin (20 mg/kg. b. wt). group D were administered diclofenac sodium plus hesperidin (20 mg/kg. b. wt). group E was given diclofenac sodium plus mixture of naringin and hesperidin at a dose of 20 mg/kg b. wt. Various biochemical paramaters like ALT, AST, CK-MB, total bilirubin, albumin, LDH, ALP, uric acid, creatinine, urea, GGT, GSH, LPO, SOD, GPx, IL-17, IL-4 , TNF-α , P53 and caspase 3 were detected. Histopathologic changes of liver, kidney and heart were also evaluated.
Results:
The administration of diclofenac for 4 weeks induced a significant increase in serum ALT, ALP, GGT, total bilirubin levels while the administration of diclofenac induced a non-significant change in serum albumin level. On the other hand, the treatment of naringin induced a highly significant decrease in serum GGT activity and total bilirubin level. The treatment of naringin induced a non-significant change in serum ALT activity and albumin level and highly significant decrease in serum ALP activity. The administration of hesperidin induced a highly significant decrease in ALT and GGT activities and total bilirubin level. Also, the administration of hesperidin induced a non- significant change in serum ALP activity and albumin level. The administration of their mixture induced a significant decrease in ALT and GGT activities as well as total bilirubin level.
On the other hand, the administration of diclofenac for 4 weeks induced a significant increase in urea, uric acid and creatinine while the treatment of naringin, hesperidin and their mixture induced a significant decrease in the the levels of these parameters.
The administration of diclofenac for 4 weeks induced a significant increase in serum AST, CK-MB and LDH activities while the treatment of naringin, hesperidin and their mixture induced a significant decrease in these enzyme activities.
The administration of diclofenac for 4 weeks induced a significant increase in LPO and significant decrease in GSH content and SOD and GPx activities in liver, kidney and heart. The administration of naringin induced a significant decrease in LPO. The administration of naringin induced a significant increase in SOD and GPx activities. The treatment of hesperidin induced a significant decrease in LPO and produced a significant effect on GSH content, but the treatment of hesperidin induced a significant improvements in SOD and GPx activities. The administration of their mixture induced a significant decrease in LPO and produced a significant increase in SOD and GPx activities and significant effect in GSH content.
The administration of diclofenac for 4 weeks induced a significant increase in serum TNF-α and IL-17 levels but it produced a significant decrease in serum IL-4 level. The treatment of naringin, hesperidin and their mixture induced a significant decrease in TNF-α and IL-17 levels and significant increase in IL-4 level.
The administration of diclofenac for 4 weeks induced a significant increase in liver p53 and caspase-3. The treatment of naringin and their mixture induced a significant decrease in liver p53 and caspase-3 expressions. Similarly, administration of hesperidin induced a significant decrease in p53 in caspase-3 expression.
The histological changes for liver of diclofenac-administered rats exhibited marked changes like hydropic degeneration of hepatocytes and portal infiltration with mononuclear cells. The kidney of diclofenac-administered rats exhibited marked changes like peritubular, periglomerular, necrosis and perivascular inflammatory cells infiltration. The heart of diclofenac-administered rats exhibited marked changes like focal necrosis of cardiac myocytes. The administration of naringin, hesperidin and their mixture reduced liver, kidney and heart disorders.
Conclusion:
This study demonstrated potential preventive effects of naringin, hesperidin and their mixture against diclofenac-induced liver, kidney and heart toxicities. The combinatory effects of naringin and hesperidin seemed to be more potent. The preventive effects may be mediated via the anti-inflammatory, antioxidant and anti-apoptotic effects of these flavonoids.