Previous studies have shown that Tau supplementation provides beneficial effects against various hepatotoxic substances such as arsenic (Li et al. 2017), lead (Flora et al. 2004) and mercury (Jagadeesan &Sankarsami Pillai 2007). In this study, Tau has been observed to reverse Cd induced weight loss, and ameliorate the pathological lesions in hepatocyte. In addition, Tau reduced the levels of ALT and AST in serum and the mRNA expressions of TNF-α and IL-1β in liver tissue. Moreover, we revealed that Tau attenuated Cd-induced hepatocyte apoptosis. Our results suggest that Tau could prevent Cd induced hepatotoxicity by inhibiting inflammation and apoptosis.
Body and organ weights are important indexes to reflect animal health status and organ toxicity(Abdel-Wahab 2014, Crissman et al. 2004, Yuet Ping et al. 2013). Studies have shown that Cd exposure can significantly decrease the weight of mice (Yang et al. 2019). In this research, we observed that Tau reversed the inhibitory effect of Cd on weight gain. In addition, we showed that Cd caused significant damage to the histological features of liver. That is in line with (Cao et al. 2017) and (Gong et al. 2019), which reported that Cd exposure resulted in swelling, coagulative necrosis and ballooning degeneration of hepatocytes. However, Tau treatment reversed these cellular abnormalities and kept the liver histologically almost normal. These findings are also supported by studies that Tau supplementation reduced bisphenol A-induced liver injury (Uzunhisarcikli &Aslanturk 2019).
Hepatic injury is directly reflected by the elevated serum hepatic enzymes, such as AST, ALT, and LDH (Gong et al. 2019, Hwang &Wang 2001). In the present study, the serum ALT and AST were significantly increased after Cd administration, which were markedly ameliorated by Tau, indicating Tau has the protective effect on Cd-induced liver injury. This result is also reported by other papers that Tau significantly reduced the levels of AST and ALT in serum of rats induced by Cd (Hwang &Wang 2001).
Studies have demonstrated Cd can induce oxidative damage in different tissues by enhancing membrane lipid peroxidation and changing cellular antioxidant system(Amamou et al. 2015, Dai et al. 2020, Ren et al. 2019). In this study, the activities of GSH were significantly increased in the liver of Cd-treated mice. However, The hepatic SOD and MDA content was not affected by Cd treatment. These results are in line with previous studies (Liu et al. 2015), which reported that the hepatic GSH contents increased significantly and the MDA content was not affected after Cd exposure. On the contrary, other studies have shown that Cd induced liver injury was accompanied by a significant increase in MDA levels, while GSH levels and SOD activities were significantly decreased (Eşrefoglu et al. 2007). These different results may be attributed to the difference of dosage, time and method of Cd treatment. More importantly, Tau administration failed to restore the increase in GSH, which indicated, to a certain extent, that the endogenous antioxidant capacity of liver was in a compensatory state.
TNF-α, produced by activated macrophages, is a mediator of local and systemic inflammation (Olszowski et al. 2012, Tracey 2002). IL-1β and IL-6 plays an important role in transmitting information, activating and regulating immune cells, mediating the activation, proliferation and differentiation of T and B cells, and in inflammatory response (Låg et al. 2010, Olszowski et al. 2012). Cd causes up-regulation of different inflammatory markers such as TNF-α and IL-6, -8, -1β, which are involved in Cd induced inflammation, apoptosis and cancer development (Lee &Lim 2011).
It was also observed in our study that these cytokine levels were significantly increased in the Cd administered. Similar results also demonstrated by (Liu et al. 2015), who found that the mRNA expression level of TNF-α, IL-6 and IL-1β in the liver were elevated after Cd exposure. Tau has been shown to inhibit TNF-α, IL-6, and TGF-β1 secretion in CCl4 induced rat liver damage (Abdel-Moneim et al. 2015). Liu et al (Liu et al. 2017) also reported that Tau protects rat liver by relieving the inflammatory response and oxidative stress induced by lipopolysaccharide. In our study, Tau significantly decreased the transcription level TNF-α and IL-1β.
The anti-apoptotic protein Bcl-2 and the pro-apoptotic protein Bax belong to the Bcl-2 protein family, which regulate mitochondrial outer membrane permeability and are the main target molecules in the study of apoptosis mechanism (Shimizu et al. 2000, Vyssokikh et al. 2002). Tau has been shown to downregulate Bax and caspase 3 expression and upregulate Bcl-2 expression in ethanol induced hepatocytes(Wu et al. 2018). In the presented work, we showed that Cd up-regulated the expression of Bax and cleaved caspase-3 while down-regulated the expression of anti-apoptotic Bcl-2. This result is in agreement with(Baiomy &Mansour 2016, Elmallah et al. 2017, Zhou et al. 2013). Tau treatment could, however, effectively reduce the level of apoptosis. That is in line with that Tau treatment protects mouse liver against arsenic-induced apoptosis (Li et al. 2017).
In conclusion, the present study demonstrated that Tau has protective function against Cd induced liver injury. The underlying mechanisms are mainly through anti-inflammatory and anti-apoptotic effects. However, further experiments are needed to investigate the exact mechanism of Tau protection against Cd hepatotoxicity and to elucidate its pharmacological functions in liver diseases.