Alpha-lipoic acid treatment of acetaminophen-induced rat liver damage

Mahmoud, Yomna I.; Mahmoud, Amor; Nassar, Gamal Eldin

doi:10.3109/10520295.2015.1063005

Cited by 17 publications

(12 citation statements)

References 32 publications

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“…In line with this finding, Galal et al, [16], Alipour et al, [28], Lee et al, [29], Mahmoud et al, [30] and Bektur et al, [31] previously reported that APAP caused marked liver damage as noted by significantly increased activities of serum AST and ALT. Moreover, Hu et al, [32] found high APAP dose caused ALT release, necrosis, irreversible mitochondrial dysfunction, and hepato-cellular death.…”

Section: Discussionsupporting

confidence: 56%

Carvedilol Could Ameliorate Acetaminophen Overdose Hepatotoxicity. Endogenous H2S Contributes Such Effect: A Comparative Biochemical Evaluation

Allam¹,

Shoman²

2017

Am. J. Biomed. Sci.

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This study was designed to evaluate the effect of acute overdose of acetaminophen exposure, and determine the curative effect of carvedilol and explore the role of endogenous H 2 S. Four groups of rats (n=10): groups I: control group, group II: acetaminophen (APAP) hepatotoxictoxic group, group III: APAP hepatotoxictoxic + carvedilol (CVD) treated group and group IV: APAP hepatotoxictoxic + CVD + hydrogen sulfide (H 2 S) blocker; dl-propargylglycine (PAG) treated group. Animals of groups II, III, IV were given a single overdose of APAP; (2 g/kg) by oral gavages. Groups III and IV received CVD (10 mg/kg/day) by oral gavages, treatment was started 1 hr before APAP administration for 14 days. Animals of group IV received intraperitoneal injection of PAG (45 µmol/kg/day) for 14 days before CVD administration. On the 15th day, blood samples were obtained for estimation of liver enzymes activity levels and animals were sacrificed. Liver was extracted for histological examination and estimation of antioxidant enzymes activity and malondialdhyde (MDA) levels in liver tissue homogenate. Serum liver enzymes activity and MDA levels were significantly higher with significantly lower antioxidant enzymes activity in group II than in groups I and III. Serum liver enzymes activity and MDA levels were significantly higher with reduced antioxidant enzymes activity in group IV than in group III. We concluded that acute acetaminophen exposure destroyed hepatic architecture and altered enzymes activity. Carvedilol has a curative effect through preserved activity of antioxidants. Endogenous H 2 S significantly contributes to carvedilol mediated effect.

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Section: Discussionsupporting

confidence: 56%

Carvedilol Could Ameliorate Acetaminophen Overdose Hepatotoxicity. Endogenous H2S Contributes Such Effect: A Comparative Biochemical Evaluation

Allam¹,

Shoman²

2017

Am. J. Biomed. Sci.

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“…This is in line with the previous data showing that the use of antioxidants such as alpha lipoic acid does not protect the liver fully from APAP-induced acute toxicity. 45 …”

Section: Discussionmentioning

confidence: 99%

Glycosphingolipids Prevent APAP and HMG-CoA Reductase Inhibitors-mediated Liver Damage: A Novel Method for “Safer Drug” Formulation that Prevents Drug-induced Liver Injury

Mizrahi¹,

Adar²,

Lalazar³

et al. 2018

Journal of Clinical and Translational Hepatology

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Background and Aims: Acetaminophen (APAP) and HMG-CoA reductase inhibitors are common causes of drug-induced liver injury (DILI). This study aimed to determine the ability to reduce APAP- and statins-mediated liver injury by using formulations that combine glycosphingolipids and vitamin E.Methods: Mice were injected with APAP or with statins and treated before and after with β-glucosylceramide (GC), with or without vitamin E. Mice were followed for changes in liver enzymes, liver histology, hepatic expression of JNK, STAT3 and caspase 3, as well as intrahepatic natural killer T cells (NKT) and the serum cytokine levels by flow cytometry.Results: Administration of GC before or after APAP alleviated the liver damage, as noted by a reduction of the liver enzymes, improvement in the liver histology and decreased hepatic caspase 3 expression. Beneficial effect was associated with a reduction of the intrahepatic NKT, JNK expression in the liver, and increased glutathione in the liver, and decreased TNF-α serum levels. Synergistic effect of co-administration of GC with vitamin E was observed. Similar protective effect of GC on statin-mediated liver damage was documented by a reduction in liver enzymes and improved liver histology, which was mediated by reduction of NKT, increased STAT3 expression in the liver, and reduced the TGF-β and IL17 levels.Conclusions: β-glycosphingolipids exert a hepatoprotective effect on APAP- and statins-mediated liver damage. Vitamin E exerted a synergistic effect to that of GC. The generation of “safer drug” formulations, which include an active molecule combined with a hepatoprotective adjuvant, may provide an answer to the real unmet need of DILI.

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“…In vitro studies suggest that ALA possesses potent biological antioxidant activities, scavenging reactive oxygen species and reactive nitrogen species as well as chelating redox-active metals (e.g., iron and copper). Due to these properties of ALA, Mahmoud et al [70] investigated the role of ALA in the treatment of acetaminophen-induced liver damage in rats. 18 rats were randomly subdivided in 3 groups: a control group, which were given 1 ml of 50% propylene glycol in water orally, an acetaminophen (APAP) group receiving 3 g/kg APA in 50% propylene glycol administered orally (acute overdose), and an ALA + APAP group receiving a single 100 mg/kg dose of ALA in 0.5% alkaline saline (0.5% NaOH) orally followed by an overdose of APAP (3 g/kg) 1 h after ALA administration.…”

Section: Possible Therapeutic Effects Of Antioxidants: From Bench mentioning

confidence: 99%

Associations of Oxidative Stress and Postoperative Outcome in Liver Surgery with an Outlook to Future Potential Therapeutic Options

Senoner

Schindler

Stättner

et al. 2019

Oxidative Medicine and Cellular Longevity

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Several types of surgical procedures have shown to elicit an inflammatory stress response, leading to substantial cytokine production and formation of oxygen-based or nitrogen-based free radicals. Chronic liver diseases including cancers are almost always characterized by increased oxidative stress, in which hepatic surgery is likely to potentiate at least in the short term and hereby furthermore impair the hepatic redox state. During liver resection, intermittent inflow occlusion is commonly applied to prevent excessive blood loss but resulting ischemia and reperfusion of the liver have been linked to increased oxidative stress, leading to impairment of cell functions and subsequent cell death. In the field of liver transplantation, ischemia/reperfusion injury has extensively been investigated in the last decades and has recently been in the scientific focus again due to increased use of marginal donor organs and new machine perfusion concepts. Therefore, given the intriguing role of oxidative stress in the pathogenesis of numerous diseases and in the perioperative setting, the interest for a therapeutic antioxidative agent has been present for several years. This review is aimed at giving an introduction to oxidative stress in surgical procedures in general and then examines the role of oxidative stress in liver surgery in particular, discussing both transplantation and resection. Results from studies in the animal and human settings are included. Finally, potential therapeutic agents that might be beneficial in reducing the burden of oxidative stress in hepatic diseases and during surgery are presented. While there is compelling evidence from animal models and a limited number of clinical studies showing that oxidative stress plays a major role in both liver resection and transplantation and several recent studies have suggested a potential for antioxidative treatment in chronic liver disease (e.g., steatosis), the search for effective antioxidants in the field of liver surgery is still ongoing.

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Alpha-lipoic acid treatment of acetaminophen-induced rat liver damage

Cited by 17 publications

References 32 publications

Carvedilol Could Ameliorate Acetaminophen Overdose Hepatotoxicity. Endogenous H2S Contributes Such Effect: A Comparative Biochemical Evaluation

Carvedilol Could Ameliorate Acetaminophen Overdose Hepatotoxicity. Endogenous H2S Contributes Such Effect: A Comparative Biochemical Evaluation

Glycosphingolipids Prevent APAP and HMG-CoA Reductase Inhibitors-mediated Liver Damage: A Novel Method for “Safer Drug” Formulation that Prevents Drug-induced Liver Injury

Associations of Oxidative Stress and Postoperative Outcome in Liver Surgery with an Outlook to Future Potential Therapeutic Options

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