Toxicological and pharmacological analysis of selenohomolanthionine in mice

Abstract

The toxic and therapeutic effects of selenohomolanthionine (4,4′-selenobis[2-aminobutanoic acid], SeHLan), a newly identified selenoamino acid found in selenized Japanese pungent radish, were compared with those of selenomethionine (SeMet) and selenite in mice. Each Se compound was injected intravenously at the dose of 0.1, 1.0, and 10 mg Se kg⁻¹ body weight. SeHLan and selenite were equally distributed to the liver and the kidneys, whereas SeMet was more preferably distributed to the liver than to the kidneys. Although a part of SeHLan was assimilated and transformed into the urinary Se metabolite, Se-methylseleno-N-acetyl-galactosamine (MeSeGalNAc), the major part of the urinary Se species was intact SeHLan. The results suggest that the metabolic capacity of SeHLan to MeSeGalNAc reached a plateau even at the lowest dose. SeMet at the highest dose significantly increased ALT and amylase activities in mice. On the other hand, treatment with SeHLan at the dose of 10 mg Se kg⁻¹ body weight significantly increased BUN and creatinine levels in mouse sera, that is, nephrotoxicity was noted. SeHLan more effectively improved the survival rate reduced by LPS treatment than selenite and SeMet at the non-toxic dose of Se. The results indicate that SeHLan may be safely and effectively used to treat sepsis in place of selenite that is currently used in the clinical setting.