5523
Passant Elwy Ibrahim Moustafa
Effects Of Liraglutide And Sulforaphane On Peripheral Neuropathy In Diabetes Induced In Rats
Liraglutide; Sulforaphane; Diabetic peripheral neuropathy; Oxidative stress; Inflammation; Matrix metalloproteinases
Diabetic peripheral neuropathy is a peripheral nerve disorder caused by diabetes mellitus. Diabetic peripheral neuropathy has a marked negative effect on patients’ quality of life as it starts with loss of limbs’ sensation and might lead to foot ulceration, gangrene and lower limb amputation. This study aimed at exploring the effect of liraglutide and sulforaphane on diabetesinduced peripheral neuropathy in rats. Experimental diabetes mellitus was induced by single intraperitoneal injections of nicotinamide (50 mg/kg) and streptozotocin (52.5 mg/kg). Eightyfour rats were allocated into seven groups. Three groups were given saline and tween 80, liraglutide (0.8 mg/kg, s.c.) or sulforaphane (1 mg/kg, p.o.). Four diabetic groups were either untreated or treated with liraglutide (0.8 mg/kg, s.c.), sulforaphane (1 mg/kg, p.o.) or pregabalin (10 mg/kg, i.p.). After two weeks of treatment, behavioral, biochemical, histopathological and immunohistochemical investigations were carried out. Treatment with liraglutide or sulforaphane restored animals’ body weight, decreased blood glucose and glycated hemoglobin levels and increased serum insulin level. In parallel, both treatments normalized motor coordination as well as the latency withdrawal time of both tail flick and hind paw cold allodynia tests and reversed the histopathological alterations. Treatment with liraglutide or sulforaphane also decreased malondialdehyde, matrix metalloproteinase-2 and-9 in the sciatic nerve. Similarly, both treatments decreased sciatic nerve nitric oxide and interleukin-6 contents, DNA fragmentation and the expression of cyclooxygenase-2 and nuclear factor kappa-B p65. Meanwhile, they increased superoxide dismutase and interleukin-10 in sciatic nerve tissue. These findings reveal that the neuroprotective effect of liraglutide and sulforaphane against peripheral diabetic neuropathy occurs probably through modulating oxidative stress, inflammation and extracellular matrix remodeling.
2018
Ph.d
Cairo
Pharmacy