Abstract
Purpose: To determine whether a combination L-carnitine and α-lipoic acid (ALA) can alleviate the toxic effects of thioacetamide (TAA) via their potent antioxidant and free radical-scavenging activities. Methods: Rats were injected with TAA for 3 days to induce acute hepatic failure. TAA induced rats were treated with each of lactulose, L-carnitine and ALA alone and a combination of L-carnitine and ALA for 3 months. Thereafter, biochemical indices, ammonia levels, oxidative stress markers, and the levels of inflammatory markers were assessed in serum, liver and brain. Results: A significant improvement was observed after 3 months of antioxidants treatment. Lactulose, L-carnitine and ALA significantly decreased serum concentrations of alanine transaminase (ALT), aspartate aminotransaminase (AST) and level of total bilirubin while both levels of total protein (TP) and albumin (ALB) were significantly increased ( p < 0.05 ) compared to TAA group. In addition, each of antioxidants alone significantly decreased ammonia (NH3) concentrations of serum, liver and brain in TAA-induced rats. Treatment with antioxidants for 3 months significantly ( p < 0.05) decreased Malondialdehyde (MDA) and nitric oxide (NO) while antioxidant enzyme activities of glutathione peroxidase (GPX) and superoxide dismutase (SOD) were significantly increased ( p < 0.05) in liver and brain tissues. The expressions of serum tumor necrosis factor-α (TNF-α) and soluble protein (S100-β) were significantly ( p < 0.05) down-regulated in TAA-induced rats. Conclusion: L-carnitine in combination with ALA can mitigate HE induced experimentally in rats. The protective efficacy of L-carnitine in combination with ALA in HE can be attributed to suppression of oxidative stress, ammonia concentration and the levels of inflammatory markers. Thus, it may have the potential to be used to treat liver cirrhosis in clinical settings. Keywords: Lactulose, L-carnitine, α-Lipoic acid, Hepatic encephalopathy, Thioacetamide, Oxidative stress, Cirrhosis, Acute liver injury
Highlights
HE is a neuropsychiatric syndrome that occurs in both cirrhosis and acute liver failure (ALF)
TAAinduced acute liver failure is used as acute liver injury model and it has been widely studied in rats and in other animal species using different doses, times and routes of administration
L-carnitine and ALA treatment rats showed that MDA and nitric oxide (NO) levels significantly declined (p < 0.05) whereas glutathione peroxidase (GPX) and superoxide dismutase (SOD) activities were significantly increased (Table 3, Table 4)
Summary
HE is a neuropsychiatric syndrome that occurs in both cirrhosis and acute liver failure (ALF). ALA and its reduced form dihydrolipoic acid (DHLA), are natural compounds widely distributed in plants and animals They are synthesized through a reaction catalyzed by lipoic acid sysnthase within the mitochondria of the liver, heart and kidney. TAA dissolved in physiological saline and induced fulminant hepatic failure through three consecutive i.p injections of TAA (100 mg/kg i.p) to rats daily for 3 consecutive days. Group (5): rats received TAA (100 mg/kg i.p) daily for 3 consecutive days and treated with lactulose Group (7): rats injected TAA (100 mg/kg i.p) daily for 3 consecutive days and treated with ALA (100 mg/kg orally) daily for 3 months (TAA+ α-lipoic acid). Group (8): rats received TAA (100 mg/kg i.p) daily for 3 consecutive days and treated with a combined dose of both L-carnitine and ALA daily for 3 months (TAA+ L-carnitine+ αlipoic acid). Ammonia (NH3) level was measured using standard kits, based on the absorbance photometry method of phenate-hypochlorate reaction
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