Hepatic cysteine sulphinic acid decarboxylase depletion and defective taurine metabolism in a rat partial nephrectomy model of chronic kidney disease

Abstract

Background Taurine depletion occurs in patients with end-stage chronic kidney disease (CKD). In contrast, in the absence of CKD, plasma taurine is reported to increase following dietary L-glutamine supplementation. This study tested the hypothesis that taurine biosynthesis decreases in a rat CKD model, but is rectified by L-glutamine supplementation. Methods CKD was induced by partial nephrectomy in male Sprague-Dawley rats, followed 2 weeks later by 2 weeks of 12% w/w L-glutamine supplemented diet (designated NxT) or control diet (NxC). Sham-operated control rats (S) received control diet. Results Taurine concentration in plasma, liver and skeletal muscle was not depleted, but steady-state urinary taurine excretion (a measure of whole-body taurine biosynthesis) was strongly suppressed (28.3 ± 8.7 in NxC rats versus 78.5 ± 7.6 μmol/24 h in S, P < 0.05), accompanied by reduced taurine clearance (NxC 0.14 ± 0.05 versus 0.70 ± 0.11 ml/min/Kg body weight in S, P < 0.05). Hepatic expression of mRNAs encoding key enzymes of taurine biosynthesis (cysteine sulphinic acid decarboxylase (CSAD) and cysteine dioxygenase (CDO)) showed no statistically significant response to CKD (mean relative expression of CSAD and CDO in NxC versus S was 0.91 ± 0.18 and 0.87 ± 0.14 respectively). Expression of CDO protein was also unaffected. However, CSAD protein decreased strongly in NxC livers (45.0 ± 16.8% of that in S livers, P < 0.005). L-glutamine supplementation failed to rectify taurine biosynthesis or CSAD protein expression, but worsened CKD (proteinuria in NxT 12.5 ± 1.2 versus 6.7 ± 1.5 mg/24 h in NxC, P < 0.05). Conclusion In CKD, hepatic CSAD is depleted and taurine biosynthesis impaired. This is important in view of taurine’s reported protective effect against cardio-vascular disease - the leading cause of death in human CKD.

Exploring the mechanism of anti-chronic heart failure effect of qiweiqiangxin І granules based on metabolomics

“…Taurine is mainly produced by a series of enzymatic reactions from methionine and cysteine. Cysteine promotes taurine production ( Huang et al, 2019 ), Cysteine sulfite carboxylase that synthesizes taurine in humans (CSAD) is considered to be the rate-limiting enzyme in mammalian taurine biosynthesis ( Abbasian et al, 2021 ), Cysteine can synthesize glutathione with glycine and glutamic acid in the body ( Forman et al, 2009 ). Our results showed that the level of taurine in the heart of the CHF model rats was increased, while decreased after QWQX І intervention.…”

Taurine is a future biomolecule for potential health benefits: A review

“…Taking dietary L-glutamine supplementation helps in elevating the level of plasma taurine, in contrast to the absence of CKD. One of the previously published studies by Abbasian et al (2021) showed in an animal model that in the case of CKD, depletion of taurine continuously occurs but it can be rectified by supplementation of L-glutamine.…”