Effect of angiotensin-converting enzyme inhibitor, lisinopril on morphological and biochemical aspects of fibrotic liver regeneration

Abstract

Background/Aims:Hepatic fibrosis results in defective liver regeneration following partial hepatectomy. Angiotensin converting enzyme (ACE) inhibitors can enhance liver regeneration and are also involved in the reduction of hepatic fibrosis. The present study has been conducted to evaluate the potential effect of an ACE inhibitor, lisinopril, on the morphological and biochemical aspects of fibrotic liver regeneration.Materials and Methods:Eight-week old female Sprague Dawley rats were made fibrotic by intragastric carbon tetrachloride treatment. Rats were given saline or lisinopril (1 mg/kg) orally for 1 week and were subjected to sham surgery or two-third partial hepatectomy. Liver regenerative and functional capacities were determined 48 hours post surgery.Results:Lisinopril administration did not affect the regeneration rate, proliferation cell nuclear antigen count, and hepatocellular area of fibrotic livers following partial hepatectomy. No statistically significant difference between treated and control rats regarding mitotic count, hepatocyte nuclear area, and binuclear hepatocyte frequency was observed. Serum biochemical analysis showed that lisinopril non-significantly decreased the partial hepatectomy induced elevated levels of alanine aminotransferase, aspartate transaminase, and alkaline phosphatase whereas lactate dehydrogenase and total bilirubin levels were significantly reduced. No marked reduction in hepatic collagen content and alpha smooth actin positive cells was observed by lisinopril treatment.Conclusion:ACE inhibitor lisinopril did not produce major histomorphological alterations in regenerating fibrotic liver following partial hepatectomy, however, it may improve its functional capability.

Perindopril Ameliorates Hepatic Ischemia Reperfusion Injury Via Regulation of NF‐κB‐p65/TLR‐4, JAK1/STAT‐3, Nrf‐2, and PI3K/Akt/mTOR Signaling Pathways

“…Angiotensin converting enzyme (ACE) inhibitors are widely used for the treatment of hypertension, cardiac remodeling, and play a crucial role in the management of mortality and morbidity associated with myocardial infarction and heart failure (Donnarumma et al, 2016). Recently, ACE inhibitors have been reported to protect against wide range of diseases including liver fibrosis (Ambreen et al, 2016;Saber et al, 2018a), lung injury (Boskabadi et al, 2019), and brain injury (El-Shoura et al, 2018). Moreover, ACE inhibitors were previously investigated during hepatic IR (Freise et al, 2006;Casillas-Ramirez et al, 2008;Yirmibesoglu et al, 2011) without exploring the exact molecular mechanisms.…”

Is serum angiotensin converting enzyme level a useful non-invasive marker for liver fibrosis in patients with chronic hepatitis C?

“…22 Measuring serum ACE levels is one of them, showing promising results in early studies, although some paradoxical outcomes have also been reported recently. [16][17][18]23 The issue of non--invasive methods has increasingly attracted many researchers, and frequently new studies on the topic are added to the literature.…”

“…14,24,25 Lisinopril has shown no major histomorphological alterations in regenerating fibrotic liver tissues and has a beneficial effect on the regression of liver fibrosis. 16 These conflicting results may also be explained by the lack of consideration of the polymorphism of ACE gene in the study population. Polymorphism of the ACE gene has the greatest impact on serum ACE levels with a strong genetic influence and large interindividual differences.…”

“…At the same time, the effect of some drugs that block the RAS system on liver fibrosis has been investigated. 15,16 However, a few studies have been conducted on the importance of serum ACE level during the stage of liver fibrosis before until now. Up to today, the measurement of serum ACE level for liver fibrosis has only been studied in the context of hepatitis B and autoimmune hepatitis, with promising results according to the authors.…”

Liver growth prediction in ALPPS – A multicenter analysis from the international ALPPS registry

“…In human, there is no evidence of the relationship of these drugs with liver regeneration, but in animals Ramalho et al describe that the losartan treatment diminished the activated stellate cell population, which is also known to participate in the liver fibrosis process 34 . On the other hand, Ambreen et al concluded that ACE inhibitor, lisinopril, did not produce major histo‐morphological alterations in regenerating fibrotic livers 48 h following partial hepatectomy in a rat model with the exception of non‐significant mitosis inhibition and increased hepatocyte binucleation 35 . However, it may improve the hepatic functional capability of fibrotic rats after surgery.…”