الفهرس 
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Abstract
In the presence of hepatic disease, the metabolic homeostasis of glucose is impaired as a result of disorders such as insulin resistance, glucose intolerance and DM. Up to 96 % of patients with cirrhosis may be glucose intolerant and 30 % may be clinically diabetic. The diabetes which develops as a complication of cirrhosis is known as “hepatogenous diabetes”. Treatment of diabetes in the cirrhotic patient is complex because of the presence of liver damage. Moreover, the hepatotoxicity induced by some oral hypoglycemic drugs may complicate such treatment. Accordingly, the pharmacological therapy must be closely monitored.
This study was developed to evaluate some possible drug interactions between insulin and N-acetyl cysteine in carbon tetra chloride-induced hepatic dysfunction in rats. It enrolled five groups of adult male albino rats on which hepatotoxicity were induced by CCl4 and then were treated with insulin and N- acetyl cysteine. Hepatotoxicity was induced in group II, III, IV &V using CCl4 (0.5 ml/kg, twice per week, for one month); while group I was left as a negative control. group II received no treatment, group III received N-acetyl cysteine (200 mg/Kg for three consecutive days), group IV received insulin (0.5U/Kg, IP) while group V received combination of insulin and N-acetyl cysteine. Blood samples were collected ,after CCl4 injection, from the retro-orbital plexus of rats to confirm hepatotoxicity induction then after the end of the experiment rats were sacrificed and blood samples were collected for measurement of liver function tests, total antioxidant capacity, insulin, glucose and adiponectin level as well as liver microsomal enzyme activity. Also, histopathological study of the liver specimens was done.
The results demonstrated that CCl4 induced hepatotoxicity in rats caused significant change in the liver functions; it led to significant increase in the levels of AST, ALT, ALP and total protein compared to normal rats. Treatment with NAC and combination of NAC and insulin caused significant reduction in the high levels of these liver enzymes. On the other hand treatment with insulin alone caused to some extent reduction in their levels.
Blood glucose level in CCl4 induced hepatotoxicity in rats had significant increase compared to normal rats. While, Treatment with either NAC alone, insulin alone or combination of NAC and insulin had significant decrease in its high level which caused by hepatic dysfunction.
Besides, CCl4 induced hepatotoxicity in rats caused significant increase in insulin level compared to normal rats. Treatment with NAC caused significant decrease in insulin high level caused by hepatic dysfunction. While, treatment with insulin alone and combination of NAC and insulin had non-significant change its level.
Regarding total antioxidant capacity, CCl4 induced hepatotoxicity in rats caused significant reduction in its level compared to normal rats. Treatment with NAC, insulin and combination of NAC and insulin caused significant elevation in its low level caused by hepatic dysfunction.
However, CCl4 induced hepatotoxicity in rats caused significant elevation in adiponectin level compared to normal rats. Treatment with NAC and combination of NAC and insulin caused significant decrease in its high level caused by hepatic dysfunction. While, treatment with insulin alone had non-significant improve in its level.
Pentobarbital (50 mg/kg, IP) was used to detect liver microsomal enzyme activity by calculation of onset and duration of sleep of the injected rats. CCl4 induced hepatotoxicity in rats caused significant more rapid in onset and longer in duration of sleeping than normal rats. Treatment with NAC did not improve the onset of sleeping, but it caused shorter in the duration of sleeping. Moreover, treatment with insulin alone had non-significant change neither in onset nor duration of sleeping. Treatment with combination of NAC and insulin caused significant improve in it; it caused delay in the onset of sleeping and shorter in the duration of sleeping.
The histopathological results revealed that the untreated group showed significant liver damage when compared to the control group, while groups treated with NAC alone and treated with insulin and NAC showed significant reduction of all histopathological changes, whereas treatment with insulin alone somewhat reduced all the histopathological changes except lobular inflammation.
Finally, it can be concluded that, in treatment of hepatic dysfunction associated with DM, application of hepatoprotective agent such as NAC in combination with antidiabetic agent as insulin would have better outcome than application of each drug alone as regarding laboratory and histopathological results. So it is recommend that when treating hepatic patients, a good control of their metabolic profile will help in improving the outcome.