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Background Heroin is a semi-synthetic opioid that is commonly abused drugs in the world. It can cause hepatic injury and lead to multiple organs dysfunction to its addicts. Only a few reports exist on the metabolic changes and mechanisms in the liver of heroin-addicted mice with hepatic injury. Methods Twelve adult male Kunming mice (30–40 g) were divided into two groups randomly. The mice in the heroin-addicted group were injected subcutaneously in the first ten days with an increased dosage of heroin from 10 mg/kg to 55 mg/kg. The dosage was then stabilized at 55 mg/kg for three days. The control group was injected with the same amount of saline in the same manner. The hepatic injury was confirmed through the combination of histopathological observation and aminotransferase (AST) and alanine aminotransferase (ALT) determination. The withdrawal symptoms were recorded and used for assessment of heroin addiction. Eventually, liver metabolic biomarkers of heroin-addicted mice with hepatotoxicity were measured using UHPLC-MS/MS. Results Biochemical analysis and histopathological observation showed that heroin-addicted mice had a liver injury. The liver metabolites of heroin-addicted mice changed significantly. Metabonomics analysis revealed 41 metabolites in the liver of addicted heroin mice as biomarkers involving 34 metabolic pathways. Among them, glutathione metabolism, taurine and hypotaurine metabolism, vitamin B2 metabolism, riboflavin metabolism, and single-carbon metabolism pathways were markedly dispruted. Conclusions Heroin damages the liver and disrupts the liver's metabolic pathways. Glutathione, taurine, riboflavin, 4-pyridoxate, folic acid, and methionine are important metabolic biomarkers, which may be key targets of heroin-induced liver damage. Thus, this study provides an in-depth understanding of the mechanisms of heroin-induced hepatotoxicity and potential biomarkers of liver damage.

Cysteine sulphinic acid (CSA), a key intermediate in the major pathway of taurine metabolism, is catabolised by cysteine sulphinic acid decarboxylase (CSA-D) to hypotaurine and by the cysteine sulphinic acid transaminase (CSA-T) to glutamate. To continue earlier studies about the latter enzyme, the CSA-T activity was measured in the developing olfactory bulb, cerebellum, whole brain and retina of C57/B16 and C3H/He inbred mice. Differences in the developmental pattern between these two strains of mice in the retinae and in the olfactory bulb were observed. The significance of the differences is discussed.

Taurine, in concentrations greater than 10 mM, was found to have an inhibitory effect on passive calcium uptake and release in rat brain synaptosomal preparations. Amino acids similar to that of taurine in chemical structure, β-alanine, hypotaurine, homotaurine and γ-amino-butyric acid were also shown to inhibit calcium uptake in this preparation. Taurine, though, did not alter the permeability of these preparations to sodium or potassium. It thus appears that taurine and chemically related amino acids can alter calcium movements in these preparations. It is postulated that this effect is due to binding to specific taurine sites in the synaptosomal membranes.

We report that mammalian tissues posses hypotaurine (2-aminoethane- sulfinate) aminotransferase activity. One product of transamination, sulfinoacetaldehyde could theoretically undergo internal oxidation-reduction leading to isethionate (2-hydroxyethanesulfonate). This hypothesis was examined. No isethionate was formed in vitro .

Hypotaurine is considered to be an intermediate in the major pathway for the biosynthesis of taurine in mammals yet is rarely detected in mammalian tissue. The activity of cysteinesulfinic acid decarboxylase, the enzyme presumably responsible for the biosynthesis of hypotaurine, is frequently present in great amounts in tissue, whereas the mechanism for the conversion of hypotaurine to taurine is poorly understood, there being some doubt at present if an enzyme exists for such a purpose. This paper reports the accumulation of hypotaurine in the liver of rats regenerating after partial hepatectomy. Further, the formation and accumulation of [ 35 S]hypotaurine from [ 35 S]methionine under the same conditions was observed. No hypotaurine was detected in liver of sham-operated control animals, even after the intraperitoneal injection of authentic hypotaurine. These observations suggest that rat liver normally possesses a mechanism for the rapid conversion of hypotaurine to taurine and that this mechanism is impeded in liver regenerating after partial hepatectomy.

The spontaneous and potassium- or veratrine-stimulated efflux of [ 35 S]hypotaurine from superfused cerebral cortex slices of adult mice was compared with the release of [ 3 H]taurine and [ 3 H]GABA. Initially GABA was the fastest released. Hypotaurine was, however, eventually released fastest, since its spontaneous efflux did not slow down during superfusions as did taurine and GABA effluxes. More than 60 % of all preloaded labelled amino acids still remained in the slices after 80-min superfusions. The effluxes of all three amino acids were stimulated by potassium and veratrine depolarizations: GABA efflux most and hypotaurine efflux least. The veratrine-stimulated release of taurine was long-lasting, while all other responses started and ended abruptly. With respect to efflux properties hypotaurine resembled more GABA than taurine.

Taurine is believed to be a modulator of membrane excitability in muscle and a neuroinhibitory transmitter in the central nervous system. The retina and pineal contain relatively large quantities of taurine. Taurine levels in the retina are reported to be responsive to variations in lighting conditions. We report here a carcadian rhythm for taurine in the mature male rat pineal gland. The maximum taurine concentration occurs at the midpoint of the light period, 24 ± 1.9 nmoles/gland, and the minimum at the beginning of the dark period, 13.9 ± 1.6 nmoles/gland. Sympathectomy by bilateral superior cervical ganglionectomy lowered pineal taurine levels. Constant light and blinding had no effect. Taurine was demonstrated to be taken up by the pineal gland in vitro in organ culture. The uptake was saturable, Km = 2.0 mM, and sodium dependent. The close structural analogs hypotaurine and β-alanine inhibited taurine uptake but α-alanine did not. We have demonstrated a circadian rhythm for taurine content in the rat pineal gland and the presence of a sodium-dependent transport system for taurine in the pineal in vitro in organ culture.

Cysteine sulfinate (CSA) carboxylyase, the enzyme which synthesizes taurine through hypotaurine, shows a higher activity in the inner plexiform and nuclear layer of adult chick retina compared to the outer plexiform and nuclear layers whereas the outer segments of photoreceptors do not show any activity of this enzyme. These observations suggest an endogenous synthesis of taurine preferentially in certain layers of retina. Therefore, taurine fulfills one more criteria which is required by a substance to be accepted as a neurotransmitter in an organ. Studies on the distribution of CSA-carboxylyase in the visual pathway and other brain areas show a very high activity of this enzyme in optic tectum followed by cerebral cortex, cerebellum, retina, lateral geniculate body and optic nerve, taken with chiasma and tract in decreasing order. On the other hand, analysis of the free amino acid pool reveals a very high content of taurine in retina as compared to optic tectum. Cysteine sulfinate carboxylyase activity and the content of taurine therefore do not seem to bear a good correlation and other mechanisms of release, uptake and degradation might be involved in regulating the taurine content in these tissues.

The effects of various amino acids and some antagonists on the electroretinogram (ERG) of isolated perfused frog retina were studied. In no case significant action on the a wave was observed. For the following compounds no influence on the b wave amplitude was detected: arginine, histidine, valine, glutamine, lysine, leucine, isoleucine, L-methionine, taurocyamine and isethionic acid. In the opposite glycine, β-alanine, GABA, L-glutamate, cysteine sulfinate, hypotaurine, taurine, homotaurine and L-phenylalanine reduced the b wave amplitude during application on the superfused retina. For all amino acids tested taurine was the most potent compound. Strychnine was found to antagonize the action of taurine but not that of GABA, whereas picrotoxin antagonized the action of GABA and not that of taurine, as it was shown in our laboratory by in vivo measurements.

Taurine, hypotaurine and the structural analogue, beta-alanine, were tested for their effects on Na+, K+-ATPase activity of crude homogenates prepared from washed cauda epididymal hamster sperm. Preincubation with 0.1–10 mM taurine or hypotaurine inhibited Na+, K+-ATPase in a dose-dependent manner, while beta-alanine had an inhibitory effect only at 10 mM. The results of this study are the first evidence to demonstrate inhibition of Na+, K+-ATPase activity by taurine and hypotaurine and are discussed in relation to the ability of these compounds to sustain hamster sperm motility and fertility.

Cultured human lymphoblastoid cells take up taurine from the medium by two processes: 1) a temperature-dependent, Na+-dependent, saturable "active"-transport system and 2) diffusion. The active transport has properties similar to those reported for taurine transport by other tissues. Apparent Km is about 25 microM and Vmax about 7.2 pmol/min/10(6) cells; saturation occurs at 100 microM taurine. Uptake is competitively inhibited by the beta-amino acids hypotaurine (50% inhibition at 44 microM) and beta-alanine (50% at 152 microM), as measured at 50 microM taurine. Taurocyamine inhibits 50% at 260 microM. Chlorpromazine and imipramine are strong uncompetitive inhibitors, giving 50% inhibition at 26 microM and 115 microM, respectively; at these concentrations cellular viability per se is not affected. Ouabain inhibits 40-50% over a concentration range of 4-500 microM. Diffusion of taurine into the cells is proportional to concentration up to 20 mM. However, at the concentration of taurine in human plasma, 40-100 microM, active transport would provide 90% of the taurine taken up.