NADH Positive Role on Early Liver Injury Caused by Acute Alcohol Exposure

NADH Potential Positive Role on Early Liver Injury Caused by Acute Alcohol Exposure

Alcohol is a kind of psychoactive substance, which has been commonly used in several cultures for centuries. Alcohol intake is the main cause of acute liver injury and chronic liver disease. Alcoholism can accelerate many types of liver diseases, for example alcoholic fatty liver disease (AFLD), alcoholic steatohepatitis, alcoholic hepatitis (AH), alcoholic live disease (ALD). As it is known, NAD+ plays an important role in the metabolism and detoxification of alcohol. Considering that NADH is the reduced form of NAD+ which is an important precursor of NAD+, NADH is beneficial for the prevention or treatment of alcohol-induced acute liver injury.

1. NADH alleviate acute alcohol-induced hepatotoxicity

The researchers administered NADH to mice 15 minutes prior to acute alcohol ingestion and observed the effects on liver function. The concentrations of ethanol and acetaldehyde in blood, the duration of the loss of righting reflex (LORR), and the levels of liver marker enzymes in plasma, such as aspartate transaminase (AST) and alanine aminotransferase (ALT), which are known as sensitive biochemical markers of early liver damage were measured. (as shown in figure 1)

nadh on alcohol mice

Figure 1 
The researchers found that NADH and NRH significantly reduced the increase of serum AST and ALT after alcohol administration (as shown in figure 1), indicating that NADH has a certain therapeutic effect on alcoholic hepatotoxicity besides preventing the adverse effects caused by alcohol. Researchers also assessed the histological characteristics of liver tissues in different groups of mice and found that NADH and NRH could alleviate alcoholic liver injury.

2. NADH increase NAD+ levels in liver tissue

The researchers injected NADH, NRH, NMN, or vehicle alone intraperitoneally into mice and assessed the content of NAD+ in kidney and liver 4 hours later. The results showed that NADH, NRH, and NMN could significantly increase the content of NAD+ in kidney, among which NADH had the strongest effect, reaching 350%. In the liver, NADH increased the concentration of NAD by 680%, Therefore, at the same dose, NADH provides a greater increase in NAD+ than NRH and NMN, while in the liver it provides a rather significant increase in NAD+ at low doses, which is consistent with the improvement of pharmacological efficacy compared with other NAD+ precursors. (as shown in figure 2)
NADH enhanced tissue NADþ levels in  vivo.
Figure 2  

3. NADH has a protective effect against oxidative stress-induced cell death

 Figure 3

The researchers exposed C2C12, Neuro2a, and AML12 cells to oxidative stress by treating them with hydrogen peroxide (H2O2) and then assessed the protective effect of NADH on cell survival.

The results showed that NADH could significantly increase cell viability and reduce cell death induced by H2O2. The researchers also measured the levels of apoptosis markers, such as Annexin V and caspase 3/7, and found that there was no significant difference between the control group and the NADH-treated group, indicating that NADH did not induce apoptosis in cells. These results suggest that NADH has a protective effect against oxidative stress-induced cell death. 

Overall, the study suggests that NADH may have potential as dietary supplements or pharmacological agents for the prevention and treatment of early liver injury caused by acute alcohol exposure. The study also provides evidence that NADH and NRH can increase NAD+ levels in liver tissue and that NADH may have a protective effect against oxidative stress-induced cell death.

Wu, K., Li, J., Zhou, X., Zhou, F., Tang, S., Yi, L., Wu, Y., & Tian, S. (2021). NADH and NRH protect against acute alcohol-induced hepatotoxicity by enhancing NAD+ levels. Journal of Functional Foods, 87, 104852.

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