Serotonin syndrome associated with methadone and milk thistle seeds: a case report

Abstract Background Serotonin syndrome is rarely, potentially life threatening condition, associated with use of serotonin acting medications and psychoactive drugs. In the majority of cases the symptoms occur soon after the initiation of a new drug or a change in the dose. Objective To present a case report and to describe the possible mechanism of development of serotonin syndrome during the interactions between milk thistle seeds and methadone on hepatic cytochrome enzyme system P450. Methods A case report of a young man on regular therapy with methadone, who develop a serotonin syndrome after ingestion a high dose of milk thistle seeds. Results Commercial preparations of milk thistle include the extract silibinin, which exhibits no beneficial or harmful drug interactions at normal doses, but at higher concentrations it can lead to dose-dependent effects on methadone metabolism, through inhibition of CYP3A4 and P-glycoprotein. As a result, it may lead to enhanced serotonin re-uptake inhibition and increased serotonin activity. Discussion Milk thistle is widely used and recommended for detoxification, but it may have serious and life threatening interactions with psychotropic drugs and psychoactive substances when used in high doses.

Evaluation of silybum marinaum efficacy on University of Wisconsin and histidine-tryptophan-ketoglutarate solutions latter the damage of the perfused liver

Abstract Purpose: To investigate the hepatoprotective and antioxidant effeicacies of Silybum marianum's (silymarin, S) on University of Wisconsin (UW) and histidinetryptophan-ketoglutarate (HTK) preservation solutions. Methods: Thirty two Wistar albino adult male rats were used. Group 1: UW group, Group 2: UW + Silymarin group(S), Group 3: HTK group, Group 4: HTK + silymarin group (S), respectively. Silymarin was enforced intraperitoneally before the surgery. Biopsies were enforced in 0, 6 and 12.hours to investigate. Results: Biochemical parameters examined in alanine aminotransferase (ALT), furthermore superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) in rats were also evaluated. Detected histopathological changings were substantially declining in the groups that received silymarin, cellular damage was decreased significantly in HTK + Silymarin group, according to other groups. It has been identified as the most effective group was HTK + silymarin group in evaluation of ALT, electron microscopic results, also decreased MDA and elevated in SOD, and CAT activity. Caspase 3 analysis showed a substantial lower apoptosis ratio in the silymarin groups than in the non-performed groups (p<0.05). Conclusion: Histidinetryptophan-ketoglutarate+silymarin group provides better hepatoprotection than other groups, by decreasing the hepatic pathologic damage, delayed changes that arise under cold ischemic terms.

Effects of silibinin and ethanol on skeletal muscle ischemia-reperfusion injury

PURPOSE: To investigate the potential beneficial effect of silibinin in ischemia-reperfusion injury (IRI) of skeletal muscle. METHODS: Under urethane anesthesia, four experimental groups were established in Balb/c mice: I) Sham-control, II) IRI (Tourniquet-induced) (2+1 h), III) IRI+ethanol (10%), and IV) IRI+silibinin (50 mg/kg/IP). The viability of muscle (left) was evaluated by the triphenyltetrazolium chloride dye method and calculated as the percentage of the contralateral control muscle (right). Malondialdehyde, superoxide dismutase, and catalase were measured in the gastrocnemius muscle via a spectrophotometer. RESULTS:The viability of gastrocnemius muscle in group II was significantly lower in comparison with that seen in group I. The administration of either ethanol or silibinin rendered the tissues to recover nearly to the baseline level. Additionally, malondialdehyde levels were higher in group II than those in group I. The application of silibinin prior to the reperfusion attenuated these to the control levels. However, malondialdehyde levels in the ethanol administrated group were reduced as well. The enhanced superoxide dismutase activity seen in the IRI group was not diminished in the animals treated with either silibinin or ethanol. Similarly, there were no differences between groups regarding the catalase activities. CONCLUSION: Ethanol seems to be effective in attenuating IRI in skeletal muscle and no definite conclusion can be made on silibinin effect.

Pharmacological effects of Silymarin extracted from introduced milk thistle fruits (Silybum marianum (L.) Gaertn.)

Study on the pharmacological effects of Silymarin extracted from introduced milk thistle fruits (Silybum marianum (L.)) collected at Sa Pa and Ha Noi in June 2002. Results: the silymarin product had chronic anti-inflammatory effects in experimental tumor model, inhibited formation of granuloma with the rate of 28.69% compared with control rats; had hepatic protection effect, decreased GPT enzyme activity and serum bilirubine of rats with 36.19% and 38.18%, respectively, in CCl4 poisoned model compared with control rats; increased bile flow up 32.25% compared with this before receiving silymarin and 49.88% compared with rats without drug, but didn’t change the bile quality