الفهرس 
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Abstract
Hepatic encephalopathy (HE) describes the array of neurological alterations that occur during acute
or chronic liver injury. Hyperammonemia, oxidative stress and inflammatory injury are the main crucial
factors for the pathophysiological changes associated with HE in rats. The present study was designed to
evaluate the possible synergistic effect between aminoguanidine (AG; 100 mg/kg; p.o.) and l-carnosine
(CAR; 200 mg/kg; p.o.) on HE that was induced by thioacetamide (TAA; 100 mg/kg.i.p) thrice weekly for
six consecutive weeks. Twenty-four hours after the last treatment; Behavioral changes, biochemical
parameters, histopathological analysis, immunohistochemical and ultrastructural studies were conducted.
The obtained results showed that combining AG with CAR improved TAA-induced locomotor impairment
and motor incoordination evidenced by; reduced locomotor activity and decline in motor skill performance
as well as ameliorated cognitive deficits. Moreover, both drugs restored the levels of serum hepatic enzymes
as well as serum and brain levels of ammonia. In addition to, the combination significantly modulated
hepatic and brain oxidative stress biomarkers, inflammatory cytokines and cleaved caspase-3 expression.
Furthermore, they succeeded to activate nuclear erythroid 2-related factor 2 (Nrf2) expressions, heme
oxygenase-1 (HO-1) activity and ameliorate markers of HE including hepatic necrosis and brain astrocyte
swelling. This study depicts that combining AG with CAR exerted new intervention for hepatic and brain
damage in HE due to their complementary antioxidant, anti-inflammatory effect and hypoammonemic
effects via Nrf2/HO-1activator and NO inhibitors.