The protective potential of metformin against acetaminophen-induced hepatotoxicity in BALB/C mice

Saravi, Seyed Soheil Saeedi; Hasanvand, Amin; Shahkarami, Kourosh; Dehpour, Ahmad Reza

doi:10.1080/13880209.2016.1185633

Cited by 43 publications

(24 citation statements)

References 51 publications

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“…It is worth noting, however, that metformin is not intrinsically hepatotoxic and can be safely administered even in the context of mildly abnormal transaminases[ 137 ]. In fact, animal studies have revealed a protective potential of metformin against acetaminophen-induced hepatotoxicity[ 138 , 139 ]. Additionally, MALA is an exceedingly rare condition with an estimated incidence of < 10 per 100000 patient-years of exposure in patients without significant renal impairment[ 140 ].…”

Section: Management Of Diabetes In Patients With Liver Diseasesmentioning

confidence: 99%

Clinical implications, diagnosis, and management of diabetes in patients with chronic liver diseases

Chung

Promrat

Wands

2020

WJH

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Diabetes mellitus (DM) negatively affects the development and progression of chronic liver diseases (CLD) of various etiologies. Concurrent DM and CLD are also associated with worse clinical outcomes with respect to mortality, the occurrence of hepatic decompensation, and the development of hepatocellular carcinoma (HCC). Unfortunately, early diagnosis and optimal treatment of DM can be challenging, due to the lack of established clinical guidelines as well as the medical complexity of this patient population. We conducted an exploratory review of relevant literature to provide an up-to-date review for internists and hepatologists caring for this patient population. We reviewed the epidemiological and pathophysiological associations between DM and CLD, the impact of insulin resistance on the progression and manifestations of CLD, the pathogenesis of hepatogenic diabetes, as well as the practical challenges in diagnosis and monitoring of DM in this patient population. We also reviewed the latest clinical evidence on various pharmacological antihyperglycemic therapies with an emphasis on liver disease-related clinical outcomes. Finally, we proposed an algorithm for managing DM in patients with CLD and discussed the clinical and research questions that remain to be addressed.

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Section: Management Of Diabetes In Patients With Liver Diseasesmentioning

confidence: 99%

Clinical implications, diagnosis, and management of diabetes in patients with chronic liver diseases

Chung

Promrat

Wands

2020

WJH

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“…These findings go in hand with Galal et al, [16] and Somanawat et al, [26] who reported that APAP caused a significant decrease in liver GSH and GPx activity which paralleled the increase in MDA levels and with Alipour et al, [28] who detected increased tissue levels of lipid peroxidation products with decreases in hepatic levels of reduced GSH, GSH peroxidase and reductase. Recently, Ding et al, [4] reported disturbed hepatic tissue antioxidant activities with increasing hepatic MDA contents and reducing hepatic tissue SOD, GSH-PX and GSH activity, Saeedi Saravi et al, [33] also reported that oral APAP decreased GSH and SOD activities.…”

Section: Discussionmentioning

confidence: 99%

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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“…Thus, metformin can potentially reduce adverse cardiac remodeling in hypertensive heart disease (41). Saeedi et al also demonstrated that metformin inhibited inflammatory cytokines, oxidative stress and necrosis by acetaminophen-induced hepatotoxicity in mice through hepatocytes protection and an antiinflammation and antioxidative mechanism (42). There is clear evidence that metformin can decrease cell death in cerebral ischemia (43).…”

Section: The Novel Beneficial Effectsmentioning

confidence: 99%

Administration of metformin in clinical medicine; an updated mini-review on current findings

Hedaiaty

2018

J Nephropharmacol

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Metformin is in the biguanide class that has been considered as the treatment for insulin resistance diabetes and polycystic ovarian disease. Many mechanisms have been suggested for it such as inhibition of the mitochondrial respiratory chain and mitochondrial glycerophosphate dehydrogenase, activation of adenosine monophosphate-activated protein kinase, inhibition of glucagon-induced elevation of cyclic adenosine monophosphate with reduced activation of protein kinase A, an effect on gut microbiota and activation of adenosine monophosphateactivated protein kinase. Metformin is a suppressor for transforming growth factor-β1 via directly binding and interact with transforming growth factor-β1 receptor. Lactic acidosis is one of the adverse and noxious effects of metformin. Nowadays, metformin has an important role in inflammation pathways and antioxidant pathways that can prevent or decrease kidney fibrosis, cardiac remodeling in hypertensive heart disease, and cell death in cerebral ischemia, kidney crystal formation, immunological diseases and cancer. Although there has been strong evidence for the potential harm caused by metformin, several studies have shown beneficial effects for it. Hence, it is necessary to revision and modification in contraindications for prescription of this drug

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The protective potential of metformin against acetaminophen-induced hepatotoxicity in BALB/C mice

Abstract: The results suggest metformin protects hepatocytes against acute acetaminophen toxicity. Metformin is indicated to diminish oxidative stress, proinflammatory cytokines, and hepatocyte necrosis.

Cited by 43 publications

References 51 publications

Clinical implications, diagnosis, and management of diabetes in patients with chronic liver diseases

Clinical implications, diagnosis, and management of diabetes in patients with chronic liver diseases

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

Administration of metformin in clinical medicine; an updated mini-review on current findings

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