Taurine mitigates cirrhosis-associated heart injury through mitochondrial-dependent and antioxidative mechanisms

Abstract

Cirrhosis-induced heart injury and cardiomyopathy is a serious consequence of this disease. It has been shown that bile duct ligated (BDL) animals could serve as an appropriate experimental model to investigate heart tissue injury in cirrhosis. The accumulation of cytotoxic chemicals (e.g., bile acids) could also adversely affect the heart tissue. Oxidative stress and mitochondrial impairment are the most prominent mechanisms of bile acid cytotoxicity. Taurine (Tau) is the most abundant non-protein amino acid in the human body. The cardioprotective effects of this amino acid have repeatedly been investigated. In the current study, it was examined whether mitochondrial dysfunction and oxidative stress are involved in the pathogenesis of cirrhosis-induced heart injury. Rats underwent BDL surgery. BDL animals received Tau (50, 100, and 500 mg/kg, i.p.) for 42 consecutive days. A significant increase in oxidative stress biomarkers was detected in the heart tissue of BDL animals. Moreover, it was found that heart tissue mitochondrial indices of functionality were deteriorated in the BDL group. Tau treatment significantly decreased oxidative stress and improved mitochondrial function in the heart tissue of cirrhotic animals. These data provide clues for the involvement of mitochondrial impairment and oxidative stress in the pathogenesis of heart injury in BDL rats. On the other hand, Tau supplementation could serve as an effective ancillary treatment against BDL-associated heart injury. Mitochondrial regulating and antioxidative properties of Tau might play a fundamental role in its mechanism of protective effects in the heart tissue of BDL animals.

Keywords: amino acid; bioenergetics; cardiomyopathy; cirrhosis; heart failure; mitochondrial impairment.

Fig. 1

Serum biomarkers of organ injury in bile duct ligated (BDL) rats. Data are given as mean ±SD (n = 8)

Fig. 2

Biomarkers of oxidative stress in the heart tissue of bile duct ligated (BDL) rats. Data are given as mean ±SD (n = 8)

Fig. 3

Mitochondrial indices of functionality in the heart tissue of bile duct ligated (BDL) rats. Data are given as mean ±SD (n = 8)

Fig. 4

Rat liver and heart tissue histopathology in control and bile duct ligated (BDL) rats. Significant tissue necrosis, bile duct proliferation, and inflammatory cell infiltration were evident in the liver of BDL animals. Liver histopathological alterations confirmed the occurrence of cirrhosis in the BDL model. Significant tissue inflammation was the most noticeable heart tissue histopathological change in BDL animals. Taurine treatment (50, 100, and 500 mg/kg) decreased heart tissue inflammation in BDL rats

Fig. 5

Cirrhosis-associated complications could proceed to a battery of molecular events in the heart muscle, which finally lead to cardiac dysfunction. Oxidative stress and mitochondrial impairment seem to play a fundamental role in cirrhosis-induced heart injury. Taurine supplementation could regulate mitochondrial function and oxidative stress in the heart tissue of cirrhotic animals.