Effects of S-adenosylmethionine on hepatic regeneration after partial hepatectomy in the rat

Fernández, L.M. Rodríguez; Pérez, Virginia; Muñoz, Mauricio Pastor; Corpa, J. M.; Abad, M.; Carbajo, M.

doi:10.1007/bf03179869

Cited by 5 publications

(4 citation statements)

References 6 publications

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“…In addition to transmethylation reactions, SAMe also participates in the transsulfuration pathway to aid in the replenishment of GSH (Lu, 2000). SAMe is known to participate in polyamine synthesis which has a critical role in enhancing liver regeneration following partial hepatectomy (Fernandez et al, 2003; Brosnan and Brosnan, 2006). Polyamine synthesis and the ability to aid in liver regeneration are both unique properties that SAMe possesses over NAC as a potential therapeutic intervention.…”

Section: Introductionmentioning

confidence: 99%

Novel protective mechanisms for S-adenosyl-l-methionine against acetaminophen hepatotoxicity: Improvement of key antioxidant enzymatic function

et al. 2012

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Acetaminophen (APAP) overdose leads to severe hepatotoxicity, increased oxidative stress and mitochondrial dysfunction. S-adenosyl-L-methionine (SAMe) protects against APAP toxicity at a mmol/kg equivalent dose to N-acetylcysteine (NAC). SAMe acts as a principle biological methyl donor and participates in polyamine synthesis which increase cell growth and has a role in mitochondrial protection. The purpose of the current study tested the hypothesis that SAMe protects against APAP toxicity by maintaining critical antioxidant enzymes and markers of oxidative stress. Male C57Bl/6 mice were treated with vehicle (Veh; water 15 ml/kg, ip), SAMe (1.25 mmol/kg, ip), APAP (250 mg/kg, ip), and SAMe + APAP (SAMe given 1 h following APAP). Liver was collected 2 and 4 h following APAP administration; mitochondrial swelling as well as hepatic catalase, glutathione peroxidase (GPx), glutathione reductase, and both Mn- and Cu/Zn-superoxide dismutase (SOD) enzyme activity were evaluated. Mitochondrial protein carbonyl, 3-nitrotyrosine cytochrome c leakage were analyzed by Western blot. SAMe significantly increased SOD, GPx, and glutathione reductase activity at 4 h following APAP overdose. SAMe greatly reduced markers of oxidative stress and cytochrome C leakage following APAP overdose. Our studies also demonstrate that a 1.25 mmol/kg dose of SAMe does not inhibit CYP 2E1 enzyme activity. The current study identifies a plausible mechanism for the decreased oxidative stress observed when SAMe is given following APAP.

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Section: Introductionmentioning

confidence: 99%

Novel protective mechanisms for S-adenosyl-l-methionine against acetaminophen hepatotoxicity: Improvement of key antioxidant enzymatic function

et al. 2012

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“…Nevertheless, SAMe treatment in both doses did not change the GSH content. Similarly, the increase in GSH content was not observed after hepatectomy in rats that were pretreated with SAMe at 10 mg/kg (Fernández et al 2003).…”

Section: Discussionmentioning

confidence: 87%

Effect of S-adenosylmethionine on liver regeneration induced by partial hepatectomy

Kohoutek

Červinková²,

Kučera³

et al. 2010

gpb

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Abstract. S-adenosylmethionine (SAMe) is a key metabolite regulating growth, differentiation and death of hepatocytes. Experimentally, exogenous SAMe has been documented to attenuate hepatocarcinogenesis. The aim of our study was to evaluate the effect of SAMe on proliferation of hepatocytes that are not cancerously transformed.Partial 2/3 hepatectomy (PH) was performed in rats, control animals underwent laparotomy. SAMe was injected immediately after the surgery and then at 24 h intervals for two days at 10 or 40 mg/kg. The animals were sacrificed 24, 48 and 72 h after operation and the intensity of liver regeneration was evaluated. SAMe treatment at 10 mg/kg was associated with decrease in the synthesis of liver DNA 48 h after PH, however, it was not reflected in DNA content. SAMe treatment at 40 mg/kg led to the reduction of DNA synthesis 72 h after PH followed by the diminution of DNA content. The results have documented the inhibition of the liver regeneration by SAMe that may be mediated by the suppression of liver fat accumulation. Cell GSH level correlating with the growth rate was not affected by SAMe. Prevention from the decrease in the intracellular content of SAMe, as a factor attenuating regeneration remains to be verified.

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“…The beneficial effects of SAMe were also reported in the treatment of osteoarthritis, where SAMe demonstrated some anti-inflammatory effect, resembling nonsteroidal anti-inflammatory drugs [46]. The most investigated and prominent therapeutic effect of SAMe is in alcoholic hepatitis and cirrhosis [47][48][49].…”

Section: Methyl Donors and Major Depression Disorder (Mdd)mentioning

confidence: 99%

S-Adenosine Methionine (SAMe) and Valproic Acid (VPA) as Epigenetic Modulators: Special Emphasis on their Interactions Affecting Nervous Tissue during Pregnancy

Ornoy

Becker

Weinstein-Fudim

et al. 2020

IJMS

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S-adenosylmethionine (SAMe) is involved in many transmethylation reactions in most living organisms and is also required in the synthesis of several substances such as monoamine neurotransmitters and the N-methyl-D-aspartate (NMDA) receptor. Due to its important role as an epigenetic modulator, we discuss in some length the process of DNA methylation and demethylation and the critical periods of epigenetic modifications in the embryo, fetus, and thereafter. We also discuss the effects of SAMe deficiency and the attempts to use SAMe for therapeutic purposes such as the treatment of major depressive disorder, Alzheimer disease, and other neuropsychiatric disorders. SAMe is an approved food additive and as such is also used during pregnancy. Yet, there seems to scanty data on the possible effects of SAMe on the developing embryo and fetus. Valproic acid (VPA) is a well-tolerated and effective antiepileptic drug that is also used as a mood stabilizer. Due to its high teratogenicity, it is contraindicated in pregnancy. A major mechanism of its action is histone deacetylase inhibition, and therefore, it acts as an epigenetic modulator, mainly on the brain. This prompted clinical trials using VPA for additional indications i.e., treating degenerative brain disease such as Alzheimer disease, dementia, HIV, and even cancer. Therefore, we discuss the possible effects of VPA and SAMe on the conceptus and early postnatally, during periods of susceptibility to epigenetic modifications. VPA is also used as an inducer of autistic-like behavior in rodents and was found by us to modify gene expression when administered during the first postnatal week but not when administered to the pregnant dams on day 12 of gestation. In contrast, SAMe modified gene expression when administered on day 12 of pregnancy but not postnatally. If administered together, VPA prevented the changes in gene expression induced by prenatal SAMe administration, and SAMe prevented the gene expression changes and autistic-like behavior induced by early postnatal VPA. It is concluded that both VPA and SAMe are powerful epigenetic modifiers with antagonistic actions on the brain that will probably be used in the future more extensively for the treatment of a variety of epigenetic diseases of the nervous system.

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Effects of S-adenosylmethionine on hepatic regeneration after partial hepatectomy in the rat

Cited by 5 publications

References 6 publications

Novel protective mechanisms for S-adenosyl-l-methionine against acetaminophen hepatotoxicity: Improvement of key antioxidant enzymatic function

Novel protective mechanisms for S-adenosyl-l-methionine against acetaminophen hepatotoxicity: Improvement of key antioxidant enzymatic function

Effect of S-adenosylmethionine on liver regeneration induced by partial hepatectomy

S-Adenosine Methionine (SAMe) and Valproic Acid (VPA) as Epigenetic Modulators: Special Emphasis on their Interactions Affecting Nervous Tissue during Pregnancy

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