1. Allyl methyl disulfide (AMDS) is one of the main compounds in garlic, whereas its metabolism has not been studied yet.
2. In this work, we first identified the metabolites of AMDS in rat erythrocytes and rats using GC–MS. The transformation mechanism study among different metabolites was then conducted. The apparent kinetics of AMDS in rat erythrocytes and pharmacokinetics of AMDS by oral administration in rats were also studied.
3. The metabolic pathway study showed that AMDS was mainly metabolized in rats to allyl methyl sulfoxide (AMSO) and allyl methyl sulfone (AMSO2) through mechanisms of reduction, methylation and oxidation. The transformation mechanism study indicated that AMDS was firstly reduced to allyl mercaptan (AM) in rat erythrocytes, and then methylated to allyl methyl sulfide (AMS) by S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH), and finally oxidized to AMSO and AMSO2 by liver microsomes. The half-life of AMDS in rat erythrocytes was 6.285?±?0.014?min while the half-lives of its active metabolites AMSO and AMSO2in vivo were 18.17 and 17.50?h, respectively. Also, the large AUCs of the two active metabolites were observed, indicating potential applications of AMDS for certain pharmacological effects. 相似文献
We aimed to explore whether maternal chronic hepatitis B virus (HBV) infection certainly affects preterm labor (birth) in pregnant women. Four databases were systematically searched up to May 31, 2017, without language restriction. Any study was included if it clearly defined exposure to chronic HBV infection, reported risk of preterm labor or birth in pregnant women, and reported relative risks (RRs) or odds ratios (ORs) or provided data for estimation. RRs (or ORs) with 95% confidence intervals were pooled using random‐effects models. Statistical heterogeneity was assessed with Cochran's Q statistic and I2 statistic. Twenty‐two observational studies involving 6 141 146 pregnant women (three prospective cohort studies, n = 1 116 799; 15 retrospective cohort studies, n = 5 022 513 and four case‐control studies, n = 1834) were included. The risk of preterm labor was significantly intensified with chronic HBV infection compared with uninfected women, with substantial heterogeneity. Chronic HBV infection was also significantly associated with a 16% increase in the risk of preterm birth, with substantial heterogeneity. The risk of preterm birth significantly increased by 21% in HBsAg+/HBeAg+ pregnant women compared with uninfected pregnant women. Chronic HBV infection intensifies the risk of preterm labor and birth in pregnant women, but this conclusion should be interpreted with caution given the possibility of residual confounding and be confirmed by well‐designed studies in the future. 相似文献
Peripheral nerve injury is a common clinical problem. Nerve growth factor (NGF) promotes peripheral nerve regeneration, but its clinical applications are limited by several constraints. In this study, we found that the time-dependent expression profiles of eight let-7 family members in the injured nerve after sciatic nerve injury were roughly similar to each other. Let-7 microRNAs (miRNAs) significantly reduced cell proliferation and migration of primary Schwann cells (SCs) by directly targeting NGF and suppressing its protein translation. Following sciatic nerve injury, the temporal change in let-7 miRNA expression was negatively correlated with that in NGF expression. Inhibition of let-7 miRNAs increased NGF secretion by primary cultured SCs and enhanced axonal outgrowth from a coculture of primary SCs and dorsal root gangalion neurons. In vivo tests indicated that let-7 inhibition promoted SCs migration and axon outgrowth within a regenerative microenvironment. In addition, the inhibitory effect of let-7 miRNAs on SCs apoptosis might serve as an early stress response to nerve injury, but this effect seemed to be not mediated through a NGF-dependent pathway. Collectively, our results provide a new insight into let-7 miRNA regulation of peripheral nerve regeneration and suggest a potential therapy for repair of peripheral nerve injury. 相似文献