Synergistic effect of aminoguanidine and<scp>l</scp>-carnosine against thioacetamide-induced hepatic encephalopathy in rats: behavioral, biochemical, and ultrastructural evidence

Afifi, Nehal A.; Ramadan, A.; Erian, Emad Y.; A.Sedik, Ahmed; Amin, Mohamed M.; Hassan, Azza; Saleh, Dalia O.

doi:10.1139/cjpp-2020-0212

Cited by 11 publications

(9 citation statements)

References 62 publications

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“…This model has been used to clarify changes in the functions of the CNS in HE (Butterworth, 2011). The current data display a significant elevation in liver enzymes, ALT, AST, ALP, bilirubin, and ammonia in TAA-treated rats as reported earlier (Afifi et al, 2020;Mostafa et al, 2017). Furthermore, TAA induced oxidative stress via depleting GSH and elevating MDA in liver and brain tissues of rats, as well as, provoking an inflammatory response evidenced by increased hepatic NF-κB and IL-6 contents (El-Marasy et al, 2019).…”

Section: Discussionsupporting

confidence: 90%

“…Moreover, elevated dopamine levels were accompanied by increase in time of the beam walking test reflecting motor defect in both BDL (Jover et al, 2006;Leke et al, 2012) and TAA-induced HE (Mendez et al, 2009). Morphological changes in brain tissues were confirmed by histopathological examinations revealing neuronal degeneration in cerebellum of BDL animals, while TAA induced evident neuronal degeneration with brain edema as reported earlier (Afifi et al, 2020;El-Marasy et al, 2019;Farjam et al, 2012).…”

Section: Discussionsupporting

confidence: 66%

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Progression of hepatic encephalopathy induced by bile duct ligation versus thioacetamide in rats: Regulatory role of apigenin

Fayez¹,

Mansour²,

Saleh³

2021

J Appl Pharm Sci

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Hepatic encephalopathy (HE) is the decline in brain functions due to liver insufficiency. A high mortality rate was reported due to the rapid progression of HE from covert to overt, leading to detrimental consequences. This study aims to assess the progression of HE and the potential hepatoprotective and neuroprotective effect of apigenin (APG) in bile duct ligation (BDL) versus thioacetamide (TAA)-induced HE models in rats. Wistar albino rats were divided into eight groups; four groups for the BDL model and the other four groups for the TAA model (100 mg/kg, i.p., thrice weekly for five consecutive weeks). APG (20 mg/kg/day) or lactulose (LAC) (8 ml/kg/day), as the standard, was administered orally for three consecutive weeks starting from day 14 of the experiment. Liver enzymes, total bilirubin, serum ammonia, brain and liver glutathione and malondialdehyde, brain dopamine, hepatic interleukin-6, and nuclear factor kappa B were assessed, as well as the beam walking test and histopathological examinations were carried out. APG showed significant anti-hyperammonemic, anti-oxidant, and anti-inflammatory effects in HE groups. Additionally, improvement in behavioral test and histological image of livers and brains of HE rats treated with APG was observed. In conclusion, APG exerted a significant regulatory role compared to LAC in progression of HE in BDL and TAA models.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 66%

Progression of hepatic encephalopathy induced by bile duct ligation versus thioacetamide in rats: Regulatory role of apigenin

Fayez¹,

Mansour²,

Saleh³

2021

J Appl Pharm Sci

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“…After acclimatization, HE in the experimental groups was induced by i.p. injections of TAA (100 mg/kg/day) three alternative days per week for six weeks according to previous studies 28 . The vehicle of TAA was physiological saline (0.9% NaCl; 5 mL/kg/day).…”

Section: Methodsmentioning

confidence: 99%

“…The vehicle of TAA was physiological saline (0.9% NaCl; 5 mL/kg/day). To prevent hypoglycemia, weight loss, dehydration, electrolyte imbalance and renal failure, animals received orally 10 mg/kg/day of fluid therapy (5% dextrose containing 0.45% saline (NaCl) and 20 mEq/L of potassium chloride (KCl) to all the rats) according to previous study 28 .…”

Section: Methodsmentioning

confidence: 99%

Ameliorative effect of oregano (Origanum vulgare) versus silymarin in experimentally induced hepatic encephalopathy

Abdelghffar

El-Nashar

Fayez

et al. 2022

Sci Rep

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Hepatic encephalopathy (HE) is a deterioration of brain function in patients suffering from chronic liver disease, cirrhosis as a result of elevated blood ammonia and the production of pseudo-neurotransmitters. Herein, we investigated the chemical composition of hexane extract from Origanum vulgare (O. vulgare) leaves as well as its possible protective effects against thioacetamide (TAA)-induced HE in rats. GC–MS analysis of the extract revealed tentative identification of twenty-five compounds (82.93%), predominated by cholesten-3-one (27.30%), followed by γ-tocopherol (13.52%), α-tocopherol (5.01%), β-amyrin (5.24%) and α-amyrin (4.89%). Albino rats were distributed into seven groups (n = 7). G1 served as negative control; G2 and G3 served as controls treated with O. vulgare (100 and 200 mg/kg/p.o b.w, respectively); G4 served as TAA-positive control group (100 mg/kg/day/i.p., three alternative days per week for six weeks); G5, G6, and G7 served as TAA -induced HE rat model that received O. vulgare 100, O. vulgare 200, and silymarin (100 mg/kg of SILY, as standard drug), respectively. TAA showed depressive and anxiety-like behaviors in forced swimming test (FST) and reduction of cognitive score in elevated plus-maze test (EPMT) as well as impairment of locomotor and exploratory activities in open-field test (OFT). TAA caused a significant decline in body weight gain; however, the relative liver weight and brain water content were statistically increased. TAA-intoxicated rats showed significant increase of serum biomarker enzymes, proinflammatory cytokines, blood ammonia levels, brain serotonin, acetyl cholinesterase and cellular lipid peroxidation with significant decrease of brain dopamine, norepinephrine, antioxidant status. The hepatoprotective/neuro-protective activities of O. vulgare was found to be comparable with that of SILY in HE rats model. Where, treatment of TAA-intoxicated rats with O. vulgare attenuated anxiety, depressive-related behaviors, and reduced the biochemical changes in HE-induced by TAA. Therefore, O. vulgare could be an excellent hepato-/neuroprotective against hepatic injury and HE via improving the oxidative/inflammatory status through its antioxidant and neuro-modulatory properties and its effect is equal to that of SILY.

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“…In a different recent study that was carried out by Afifi et al on the synergistic effect of carnosine and aminoguanidine in counteracting the hepatic encephalopathy (induced by thioacetamide i.p. injection) in rats through the activation of the Nrf2/HO-1 pathway, nitric oxide inhibition was demonstrated [ 255 ]. During the last two decades, the antioxidant and anti-inflammatory effects of the carnosine analog polaprezinc, a chelated compound of zinc and L-carnosine, have also been investigated [ 256 ].…”

Section: The Therapeutic Potential Of Carnosine As An Antidote In Pre...mentioning

confidence: 99%

The Therapeutic Potential of Carnosine as an Antidote against Drug-Induced Cardiotoxicity and Neurotoxicity: Focus on Nrf2 Pathway

et al. 2022

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Different drug classes such as antineoplastic drugs (anthracyclines, cyclophosphamide, 5-fluorouracil, taxanes, tyrosine kinase inhibitors), antiretroviral drugs, antipsychotic, and immunosuppressant drugs are known to induce cardiotoxic and neurotoxic effects. Recent studies have demonstrated that the impairment of the nuclear factor erythroid 2–related factor 2 (Nrf2) pathway is a primary event in the pathophysiology of drug-induced cardiotoxicity and neurotoxicity. The Nrf2 pathway regulates the expression of different genes whose products are involved in antioxidant and inflammatory responses and the detoxification of toxic species. Cardiotoxic drugs, such as the anthracycline doxorubicin, or neurotoxic drugs, such as paclitaxel, suppress or impair the Nrf2 pathway, whereas the rescue of this pathway counteracts both the oxidative stress and inflammation that are related to drug-induced cardiotoxicity and neurotoxicity. Therefore Nrf2 represents a novel pharmacological target to develop new antidotes in the field of clinical toxicology. Interestingly, carnosine (β-alanyl-l-histidine), an endogenous dipeptide that is characterized by strong antioxidant, anti-inflammatory, and neuroprotective properties is able to rescue/activate the Nrf2 pathway, as demonstrated by different preclinical studies and preliminary clinical evidence. Starting from these new data, in the present review, we examined the evidence on the therapeutic potential of carnosine as an endogenous antidote that is able to rescue the Nrf2 pathway and then counteract drug-induced cardiotoxicity and neurotoxicity.

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Synergistic effect of aminoguanidine andl-carnosine against thioacetamide-induced hepatic encephalopathy in rats: behavioral, biochemical, and ultrastructural evidence

Cited by 11 publications

References 62 publications

Progression of hepatic encephalopathy induced by bile duct ligation versus thioacetamide in rats: Regulatory role of apigenin

Progression of hepatic encephalopathy induced by bile duct ligation versus thioacetamide in rats: Regulatory role of apigenin

Ameliorative effect of oregano (Origanum vulgare) versus silymarin in experimentally induced hepatic encephalopathy

The Therapeutic Potential of Carnosine as an Antidote against Drug-Induced Cardiotoxicity and Neurotoxicity: Focus on Nrf2 Pathway

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