Cirrhosis-induced oxidative stress in erythrocytes: The therapeutic potential of taurine

Abstract

Aim of the study: Cholestasis/cirrhosis could induce erythrocyte lysis. The incidence of various types of anemia in cirrhosis is approx. 75%. Several studies have mentioned the pivotal role of oxidative stress in this complication. Taurine (TAU) is the human body's most abundant free amino acid. TAU is known as a robust cell membrane stabilizer. Many studies have mentioned that TAU could counteract oxidative stress in various experimental models. The current study was intended to evaluate the effect of TAU on erythrocytes in cirrhotic rats.

Material and methods: Bile duct ligation (BDL) surgery was carried out on rats. Then, complete blood count (CBC), hemoglobin (Hgb), hematocrit (HTC), and erythrocytes' G6PD, catalase (CAT), and superoxide dismutase (SOD) activity were measured. Moreover, biomarkers of oxidative stress were assessed, and the erythrocytes' morphological changes were monitored in the cirrhotic mice exposed to TAU (0.25%, 0.5%, and 1% w : v in drinking water).

Results: Significant changes in the assessed erythrocyte parameters (G6PD activity, Hgb, HTC, and erythrocyte count) and red blood cells (RBC) morphological alterations were detected on day 42 after BDL surgery. Biomarkers of oxidative stress also did not change at the time points, except on post-BDL days 28 and 42. A significant decrease in blood parameters was evident at post-BDL day 42. All doses of TAU (0.25%, 0.5%, and 1% w : v in drinking water) significantly improved erythrocyte parameters and encountered oxidative stress in the erythrocytes of cirrhotic animals.

Conclusions: These data indicate that TAU could be a safe agent to mitigate cirrhosis-induced erythrocyte damage and anemia. Further investigations are necessary to prove this in clinical settings.

Keywords: anemia; bile acids; cholestasis; cirrhosis; oxidative stress; red blood cells.

Fig. 1

Plasma biochemical analysis (A) and liver tissue histopathological alterations (B; blue colored, green arrow) in bile duct ligated (BDL) rats. These data confirm the occurrence of cholestasis in the current model. Data are shown as mean ±SD (n = 7). Data sets with various alphabetical superscripts differ significantly (p < 0.05). Scale bars for histopathological images are = 100 µm

Fig. 2

Complete blood count (CBC) and hematological alterations at different time points after bile duct ligated (BDL) surgery. A significant decrease in parameters associated with red blood cells (erythrocyte count, Hgb, and HCT) was detected in BDL rats 42 days after the BDL operation. No significant changes in WBC and platelets were detected in the current model. Data are presented as mean ±SD (n = 7). Data series with different alphabetical superscripts are significantly different (p < 0.05)

Fig. 3

Role of taurine (TAU) on complete blood count (CBC, RBC) of bile duct ligated (BDL) animals (42 days after BDL surgery). Data are represented as mean ±SD (n = 7). Data series with different alphabetical superscripts are significantly different (p < 0.05)

Fig. 4

Monitoring glucose-6-deficiency (G6PD) at different intervals after bile duct ligation (BDL) surgery. A significant decrease in G6PD deficiency was detected 42 days after the BDL operation. It was found that taurine (TAU) significantly improved G6PD deficiency at both doses (0.25%, 0.5%, and 1% w : v). Data are shown as mean ±SD (n = 7). Data series with different alphabetical superscripts are significantly different (p < 0.05)

Fig. 5

The light microscope analysis of erythrocytes in bile duct ligated (BDL) rats. A significant increase in microcytic hypochromic and polychromasia erythrocytes was detected in BDL rats. Taurine (TAU) had no significant effect on the RBS morphology in the current investigation. Data are shown as mean ±SD (n = 7). Data series with different alphabetical superscripts are significantly different (p < 0.05)

Fig. 6

Oxidative stress markers were assessed in erythrocytes on days 28 (A) and 42 after bile duct ligated (BDL) surgery (B). It was found that taurine (TAU; 0.5% and 1% w : v) significantly decreased biomarkers of oxidative stress in cirrhotic rats. In the current experiments, most oxidative stress markers were not significantly changed at 3, 7, and 14 days after cholestasis induction. Data are shown as mean ±SD (n = 7). Data series with different alphabetical superscripts are significantly different (p < 0.05)

Fig. 7

Several options have been developed for managing anemia in cirrhosis in clinical settings. This figure is adapted from reference [17] (Creative Commons Attribution-NonCommercial; CC BY-NC 4.0); d – day, f – folic acid, b – bolus dose

Fig. 8

Oxidative stress and its associated complications play a critical role in the pathogenesis of cirrhosis-induced erythrocyte damage, lysis, and anemia. The accumulation of potentially cytotoxic molecules, such as hydrophobic bile acids and supraphysiological concentrations of bilirubin, could be involved in the pathogenesis of these adverse effects