Interactions of melatonin with the liver microsomal cytochrome P450 system of rats and humans in vitro and effects on the P450 system and the antioxidative status in rat liver after acute treatment

Klinger, W; Karge, E.; Demme, U.; Kretzschmar, M.

doi:10.1007/bf03190373

Cited by 1 publication

(1 citation statement)

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“…On the other hand, 6‐hydroxylation of melatonin is mediated by CYP1A1, CYP1A2 and CYP1B1 but not CYP2E1 and CYP2A6 [29]. In vitro study showed that melatonin strongly binds to CYP1A, and distinctly less to CYP2B or CYP3A [30]. We have already demonstrated that S ‐allylmercaptocysteine (SAMC), an organosulfur compound in aged garlic extract, inhibits CYP2E1 activities, resulting in reduced generation of NAPQI and suppression of GSH depletion [11].…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of protection by melatonin against acetaminophen‐induced liver injury in mice

Matsura¹,

Nishida²,

Togawa³

et al. 2006

Journal of Pineal Research

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The present study was performed to determine whether melatonin protects mouse liver against severe damage induced by acetaminophen (APAP) administration and where melatonin primarily functions in the metabolic pathway of APAP to protect mouse liver against APAP-induced injury. Treatment of mice with melatonin (50 or 100 mg/kg, p.o.) 8 or 4 hr before APAP administration (750 mg/kg, p.o.) suppressed the increase in plasma alanine aminotransferase and aspartate aminotransferase activities in a dose- and a time-dependent manner. Melatonin treatment (100 mg/kg, p.o.) 4 hr before APAP administration remarkably inhibited centrilobular hepatic necrosis with inflammatory cell infiltration and increases in hepatic lipid peroxidation and myeloperoxidase activity, an index of tissue neutrophil infiltration, as well as release of nitric oxide and interleukin-6 into blood circulation at 9 hr after APAP administration. However, melatonin neither affected hepatic reduced glutathione (GSH) content nor spared hepatic GSH consumption by APAP treatment. Moreover, pretreatment with melatonin 4 hr before APAP administration did not influence the induction of hepatic heat shock protein 70 (HSP70) by APAP and melatonin alone did not induce HSP70 in mouse liver. These results indicate that exogenously administered melatonin exhibits a potent hepatoprotective effect against APAP-induced hepatic damage probably downstream of the activity of cytochrome P450 2E1, which works upstream of GSH conjugation in the pathway of APAP metabolism, via its anti-nitrosative and anti-inflammatory activities in addition to its antioxidant activity.

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Section: Discussionmentioning

confidence: 99%