الفهرس 
Introduction& aim of the workOnly 14 pages are availabe for public view
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Abstract
The relationship between non alcoholic steatohepatitis (NASH) and depression is bidirectional and how depression affects the progression and responsiveness of NASH to treatment is controversial.
One of the potential pathological links is the JNK pathway. Accordingly our study was designed to evaluate whether the use of sitagliptin or metformin may improve NASH in non stressed and stressed rats through JNK pathway or not.
Induction of NASH in non stressed and stressed groups was associated with significant decline in: struggling time, active interaction time in SIT and decrease in number of total crossed squares in OFT, and significant increase in: immobility time of FST, central zone duration and latency to leave central zone. Similar changes appeared in rats exposed to CRS.
Chronic treatment with sitagliptin or metformin significantly improved the behavioral changes. While there was significant difference on the latency to leave central zone in stressed treated groups that favors sitagliptin, but there was significant difference on swimming time in both non stressed and stressed treated groups that favors metformin.
Induction of NASH was associated with significant increase in body weight % change in stressed rats.
Chronic treatment with sitagliptin produced significant increase in BW % change in non stressed and stressed groups. However, there was significant difference in body weight % change in non stressed treated groups that favors metformin.
Induction of NASH induced significant increase in EAT/body weight ratio and liver weight index in both non stressed and stressed groups.
Chronic treatment with sitagliptin or metformin produced significant decrease in EAT/body weight ratio and liver weight index in both non stressed and stressed groups. There was no significant difference between the two treated groups.
Induction of CRS and NASH in rats was associated with significant increase in serum total cholesterol, triglycerides, LDL, fasting glucose, fasting insulin, HOMA IR index, AST, ALT, corticosterone, and hepatic MDA levels. Significant decrease in serum HDL and adiponectin levels. These changes were exaggerated in stressed rats with NASH.
Chronic treatment with sitagliptin or metformin significantly improved the biochemical changes. However, there was significant difference in fasting insulin, LDL, AST, and hepatic MDA levels in non stressed treated groups; LDL, total cholesterol, fasting glucose, ALT and adiponectin levels in stressed treated groups that favors sitagliptin.
Induction of NASH produced significant increase in hepatic JNK mRNA expression in both non stressed and stressed groups.
Chronic treatment with sitagliptin or metformin produced significant decrease in hepatic JNK mRNA expression in both non stressed and stressed groups. However, there was a significant difference in hepatic JNK mRNA in stressed treated groups that favors sitagliptin.
Induction of NASH produced significant increase in the score of steatosis, lobular inflammation, hepatocyte ballooning, NAS, portal inflammation and fibrosis in both non stressed and stressed groups.
Chronic treatment with sitagliptin or metformin produced significant improvement in all scores in non stressed rats except the score of fibrosis.
On the other hand chronic treatment with sitagliptin or metformin produced significant improvement in hepatocyte ballooning and portal inflammation scores in stressed rats, while sitagliptin produced significant improvement in scores of steatosis, lobular inflammation and NAS.
The liver morphology showed that rats with NASH apparently displayed fat accumulation, ballooning degeneration, inflammation, increase in collagen fibers content at the portal tract, increase TNF-α expression, abnormal mitochondria and rough endoplasmic reticulum. Some of these changes were apparently observed in CRS group and exaggerated in NASH+CRS group.
Chronic treatment with sitagliptin was apparently able to reverse steatosis, inflammation, and ballooning and was apparently able to decrease collagen fibers content in the portal tract than metformin.
By electron microscopic examination, chronic treatment with sitagliptin or metformin apparently decreased mitochondrial variations, swelling, vacuolation and loss of cristae. rER was also partially improved in sitagliptin than metformin treated groups.
Immunohistochemical staining showed decrease expression of TNFα in NASH sitagliptin and NASH metformin treated groups.