الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
7. Summary
Diabetes mellitus (DM) is a chronic disease associated with serious complications, including testicular dysfunction. Umbelliferone (UMB) is a coumarin with promising antioxidant, anti-inflammatory and other beneficial effects. Pioglitazone, a thiazolidinedione derivative, is a highly selective PPARγ agonist. It is approved in the treatment of T2DM associated with insulin resistance. Recently, several studies tend to prefer the use of medicinal plant constituents as protective antidiabetic agents.
Thus, the present study aimed to assess the effects of UMB and PIO against hyperglycemia-induced testicular dysfunction in T2DM rat model induced by high fat diet (HFD) and streptozotocin (STZ).
To achieve this aim, biochemical parameters related to T2DM including serum glucose level, serum insulin level and HbA1c were measured in addition to calculation of insulin resistance indices (HOMA−IR & QUICKI). Integrity of the pituitary-gonadal axis was evaluated by measuring serum levels of FSH, LH and testosterone. Inflammatory cytokines (IL-6 & TNF-α) and lipid profile (serum TC, TGs, HDL, LDL and vLDL) were also measured in diabetic rats. In diabetic rats testicular tissue, oxidative stress markers (MDA, NO, GSH, GPx and SOD), FSHR mRNA, LHR mRNA transcripts and PPARγ expression were assayed in the following groups:
group 1: Normal control group were given the same volume of the vehicle (CMC 0.5% solution), in which the treatments were dissolved, orally for 6 weeks.
group 2: Diabetic group, the rats of this group were given the same volume of the vehicle (CMC 0.5% solution) orally for 6 weeks.
group 3: Diabetic group treated by 10 mg/kg body weight PIO dissolved in 0.5% CMC orally for 6 weeks.
group 4: Diabetic group treated by 50 mg/kg body weight UMB dissolved in 0.5% CMC orally for 6 weeks.
The obtained data revealed that treatment of diabetic rats with UMB remarkably improved the hyperglycemic state evidenced by increase of serum insulin level, decrease of HbA1c, decrease of HOMA−IR index and increase of QUICKI index. Moreover, UMB improved the pituitary-gonadal axis confirmed by increased serum levels of FSH, LH and testosterone. UMB decreased inflammatory cytokines (IL-6 & TNF-α) in diabetic rats in addition to its anti-dyslipidemic effect evidenced by decrease of serum TC, TGs, LDL, vLDL and increase of HDL. UMB suppressed testicular oxidative stress evidenced by decreased lipid peroxidation, NO, increased GSH, GPx and SOD activities. UMB upregulated FSHR, LHR and increased PPARγ protein expression level in testicular tissue. Data revealed that treatment of diabetic rats with PIO showed similar effects like UMB.
In conclusion, UMB and PIO have protective potentials against hypogonadotropic hypogonadism in T2DM. These protective effects may be mediated via control of the hyperglycemic state, suppression of inflammatory cytokines, improvement of oxidative stress and antioxidant defense system and upregulation of PPARγ expression in testicular tissue.
However, further studies are required to figure out detailed molecular mechanisms between UMB and PPARγ expression in different tissues.