Comparison of S-Adenosyl-l-methionine and N-Acetylcysteine Protective Effects on Acetaminophen Hepatic Toxicity

Abstract

Nutraceuticals are widely used by the general public, but very little information is available regarding the effects of nutritional agents on drug toxicity. Excessive doses of acetaminophen (APAP, 4-hydroxyacetanilide) induce hepatic centrilobular necrosis. The naturally occurring substance S-adenosyl-L-methionine (SAMe) has been reported to reduce the hepatic toxicity of APAP. The present study was designed to investigate the hepatoprotective effects of SAMe in comparison to the clinically used antidote N-acetylcysteine (NAC). Male C57BL/6 mice were injected intraperitoneally (i.p.) with an equimolar dose (1.25 mmol/kg) of either SAMe or NAC just before APAP, and the groups were denoted SAMeϩAPAP and NACϩAPAP, respectively. Mice were immediately injected i.p. with 300 mg/kg APAP, and hepatotoxicity was evaluated after 4 h. SAMe was more hepatoprotective than NAC at a dose of 1.25 mmol/kg as liver weight was unchanged by APAP injection in the SAMeϩAPAP group, whereas liver weight was increased in the NACϩAPAP group. SAMe was more hepatoprotective for APAP toxicity than NAC, because alanine aminotransferase levels were lower in the SAMeϩAPAP. Pretreatment with SAMe maintained total hepatic glutathione (GSH) levels higher than NAC pretreatment before APAP, although total hepatic GSH levels were lower in the SAMeϩAPAP and NACϩAPAP groups than the vehicle control values. Oxidative stress was less extensive in the SAMeϩAPAP group compared with the APAPtreated mice as indicated by Western blots for protein carbonyls and 4-hydroxynonenal-adducted proteins. In summary, SAMe reduced APAP toxicity and was more potent than NAC in reducing APAP hepatotoxicity.

An integrative genomic analysis identifies Bhmt2 as a diet-dependent genetic factor protecting against acetaminophen-induced liver toxicity

“…Within the methionine/glutathione biosynthesis pathway, methionine is converted to SAM, which is then used for cysteine and GSH biosynthesis. Administration of SAM was previously shown to attenuate APAP-induced hepatotoxicity and to preserve hepatic GSH levels in C57BL/6J mice (Bray et al 1992;Valentovic et al 2004;Terneus et al 2007). Therefore, we analyzed .…”

Therapeutic potential ofMoringa oleiferaextracts against acetaminophen-induced hepatotoxicity in rats

“…Group I: Animal received 0.5% Tween 80 only (vehicle control) Group II: Animals received 7 g APAP/kg bw and 0.5% Tween 80 Group III: Animals received 7 g APAP/kg bw and 7.35 mmol NAC/kg bw (Terneus et al, 2007) (positive control) Group IV: Animals received 7 g APAP/kg bw and 200 mg flower extract/kg bw Group V: Animals received 7 g APAP/kg bw and 400 mg flower extract/kg bw Group VI: Animals received 7 g APAP/kg bw and 200 mg leaf extract /kg bw Group VII: Animals received 7g APAP/kg bw and 400 mg leaf extract /kg bw Diet was withdrawn from the animals 16 h before sacrifice. Animals were weighed and sacrificed 24 h after the treatment using diethyl ether.…”

Reduction of Acute Hepatic Damage Induced by Acetaminophen after Treatment with Diphenyl Diselenide in Mice

“…NAC reduces hepatic damage by increasing GSH levels and antagonizing the oxidative stress induced by NAPQI (Bajt et al 2004;Kelly 1998;Mitchell et al 1973;Terneus et al 2007). However, for NAC to be effective, it must be administered quickly before the elevation of the alanine transaminase (ALT) level is seen (Latchoumycandane et al 2007).…”