The main purpose of this study was to evaluate the effect of N-acetyl cysteine on liver function in patients undergoing elective coronary artery bypass surgery.
The results of our study showed that administration of N-acetyl cysteine in patients undergoing CABG had a further decrease in the levels of ALP, AST, ALT, bilirubin, PTT, and INR after surgery, that indicating the positive effect of the drug on liver function.
Some previous studies have shown that the antioxidant and anti-inflammatory role of N-acetyl cysteine is very effective in protecting the body’s organs in many important systems, including the liver, which is consistent with our findings (13).
In a comprehensive study by Singh et al., intravenous injection of N-acetyl cysteine in all types of acute liver failure was able to significantly improve hepatic serological biomarkers (13). This study confirmed the hepatic outcomes in our research.
Didem Onk, et al., showed that the pretreatment by N-acetylcysteine can improve hepatic functions by regulation of the metabolism of the ammonia and nitrogen, and reduction of lactate in patients with chronic obstructive pulmonary disease who undergo coronary artery bypass grafting surgery(14).
Sayed et al. examined the effect of N-acetyl cysteine use on liver enzymes in patients undergoing liver surgery. The results showed that ALT and AST levels were significantly lower after surgery in the N-acetyl cysteine receiving intervention group than in the control group. They concluded that injection of N-acetyl cysteine in patients undergoing liver surgery could reduce enzyme levels and subsequent liver damage (15). The results of this study are in line with the present research.
Shafiei et al. study showed that there was a significant reduction in troponin-I and lactate level in the treatment groups (N-acetyl cysteine and melatonin) compared to the placebo arm indicating that N-acetyl cysteine and melatonin were able to prevent the post-CABG cardiac injury(16).
Beyaz et al. studied 41 patients who were candidates for laparoscopic surgery to evaluate the effect of N-acetyl cysteine use on liver function following general anesthesia. The decrease in AST, ALT, LDH, and GGT levels was lower in 1 and 24 hours after surgery than in the control group. They concluded that liver function was better maintained by using N-acetyl cysteine during general anesthesia (17).
Yazdi et al. studied the effect of N-acetyl cysteine on liver function in patients undergoing isoflurane anesthesia to investigate its effects on the hepatic complications of this type of anesthesia. They concluded that N-acetyl cysteine could significantly reduce liver enzymes compared to the control group after administration of isoflurane (18). Both of the above studies are consistent with the results of our study.
As mentioned earlier, the positive effects of this drug on liver protection are mainly attributed to its role as a precursor of glutathione and consequently its antioxidant effects (19). Also, N-acetyl cysteine has been shown to maintain the activity of catalase, mitochondrial super oxidase dismutase, and various forms of glutathione peroxidase and keep membrane fluidity. These have been suggested as mechanisms involved in the preservation of the liver during biliary obstruction in rats (20).
In the study of Jin et al. the protective effect of N-acetyl cysteine against liver damage was confirmed as it was able to inhibit the expression of TNF-α following ischemic liver damage and thereby reduce the extent of liver damage (20). Their results are consistent with the present study.
In a study by Ibrahim and Sharawy, the effect of intravenous infusion of N-acetyl cysteine in cirrhotic patients undergoing abdominal surgery was investigated. Finally, it was shown that this intervention has led to the maintenance of liver and kidney function in these patients (21).
In a study by Fusai et al. in rabbits, animals with hepatic steatosis were treated with N-acetyl cysteine. Similar to what was observed in our study, it was shown that this drug can reduce the level of ALT and, at the same time, significantly reduce liver cell damage (22).
In the study of Montero et al. in rats, the effect of N-acetyl cysteine administration on liver tissue after camp triad port was investigated. Compared with placebo, N-acetyl cysteine significantly reduced serum levels of AST and ALT (23). The findings of these two studies are consistent with the results of the present study in terms of the positive effect of N-acetyl cysteine on the reduction of liver enzymes related to liver function.
Several studies have been conducted to evaluate the protective effects of N-acetyl cysteine on vital tissues and organs in patients undergoing heart surgery.
The results of a study by Sucu et al. showed that intravenous administration of N-acetyl cysteine reduced the pump-induced inflammatory response during cardiopulmonary bypass(24).
In a study by Fathi et al., the effect of N-acetyl cysteine on liver function in patients undergoing coronary artery bypass graft surgery was investigated. The results of this study showed a decrease in liver enzymes in patients receiving N-acetyl cysteine compared to the control group. They recommended that all patients undergoing CABG receive 150 mg/kg of N-acetyl cysteine in the form of prophylaxis(25).
Ristikankare et al. examined high doses of NAC to observe the protective role of N-acetyl cysteine during cardiac surgery with CPB. Consistent with our results, the results of their study showed the beneficial effects of N-acetyl cysteine on the liver(26).
Contrary to the results of our study, Snowden and Prentis showed that the use of N-acetyl cysteine did not reduce alanine aminotransferase levels, meaning that it did not affect improving cell liver damage (27). On the other hand, in a study by Kemp et al., no significant improvement in postoperative outcomes of liver resection and hepatectomy was reported in patients receiving N-acetyl cysteine, and the drug was considered ineffective(28).
Grendar et al. evaluated the effect of N-acetyl cysteine on liver recovery after resection and hepatectomy. They found N-acetyl cysteine to be ineffective in the improvement of liver function(29).
Differences in the administration method and dosage of N-acetyl cysteine may be involved in justifying this difference. Also, differences in sample size, type of surgery, and follow-up time are other reasons for this discrepancy in the results. The present study showed improvement in liver function and liver enzyme levels in patients undergoing coronary artery bypass graft surgery. The levels of ALP, AST, and ALT enzymes were further reduced in the group receiving N-acetyl cysteine, which is of significant importance, especially in patients at risk of decreased visceral perfusion during surgery (especially during CPB) to reduce the risk of ischemia and liver damage. The results of our study showed that N-acetyl cysteine significantly improved Liver Function Test (LFT) and could be effective in reducing ischemic liver damage. This effect of N-acetyl cysteine can be due to its effects on the glutathione system (protective mechanism of the liver) or its anti-inflammatory and antioxidant effects.
Limitations
This study has several limitations. First, the sample size was small. Second, the study was single-center. We recommended further trials with large sample size, multi-center, and long follow-up duration.