Hypotaurine is a precursor for the biosynthesis of taurine and is an endogenous inhibitory amino acid of the glycine receptor [1]. Hypotaurine inhibits the GABA transporters 1 (GAT1), 2 (GAT2), 3 (GAT3), and 4 (GAT4) in mice (IC50 values are 170, 240, 4.9, and 8.1μM respectively) and GAT1, 2, and 3 in rats (IC50 values are 1010, 52, and 73μM respectively) for the uptake of GABA [2]. As an antioxidant, Hypotaurine can effectively eliminate free radicals and reactive oxygen species [3].
In vitro, Hypotaurine (1mM; 24h) significantly reduced the concentration of hydroxyl radicals in rat placental trophoblast cells (TR-TBT 18d-1) treated with H2O2, and had a protective effect against H2O2-induced oxidative damage [4]. Under high chloride conditions, Hypotaurine (30-3000μM; 100s) increased the inward current or upward deflection of membrane potential in glial cells (SG) neurons in the immature mouse tail trigeminal nucleus (Vc) in a concentration-dependent manner, with EC50 values of 663.8 and 337.6μM respectively [5].
In vivo, in rats subjected to tail swinging, paw pressing, and formalin test, Hypotaurine (100, 200, 400, and 600μg/10μL; intrathecal injection) prolonged the tail flick latency in a dose-dependent manner, alleviated mechanical hyperalgesia and thermal hyperalgesia [6]. Hypotaurine (2.4mM/kg/2mL; intraperitoneal injection) pretreatment significantly attenuated the increase in ALT, AST, and LDH activities in rat plasma induced by acetaminophen (APAP), as well as the decrease in GR, GST, and GCS activities and the consumption of GSSG in the liver [7].
References:
[1] Green TR, Fellman JH, Eicher AL, Pratt KL. Antioxidant role and subcellular location of hypotaurine and taurine in human neutrophils. Biochim Biophys Acta. 1991;1073(1):91-97.
[2] Kragler, A., Höfner, G., and Wanner, K.T. Novel parent structures for inhibitors of the murine GABA transporters mGAT3 and mGAT4. Eur. J. Pharmacol. 519(1-2), 43-47 (2005).
[3] Aruoma O I, Halliwell B, Hoey B M, et al. The antioxidant action of taurine, hypotaurine and their metabolic precursors[J]. Biochemical Journal, 1988, 256(1): 251-255.
[4] Nishimura T, Duereh M, Sugita Y, et al. Protective effect of hypotaurine against oxidative stress-induced cytotoxicity in rat placental trophoblasts. Placenta. 2015;36(6):693-698.
[5] Oh SM, Bhattarai JP, Han SK, Park SJ. Effects of hypotaurine on substantia gelatinosa neurons of the trigeminal subnucleus caudalis in immature mice. Amino Acids. 2016;48(12):2843-2853.
[6] Hara K, Nakamura M, Haranishi Y, Terada T, Kataoka K, Sata T. Antinociceptive effect of intrathecal administration of hypotaurine in rat models of inflammatory and neuropathic pain. Amino Acids. 2012;43(1):397-404.
[7] Acharya M, Lau-Cam CA. Comparison of the protective actions of N-acetylcysteine, hypotaurine and taurine against acetaminophen-induced hepatotoxicity in the rat. J Biomed Sci. 2010;17 Suppl 1(Suppl 1):S35. Published 2010 Aug 24.