Proanthocyanidins attenuated liver damage and suppressed fibrosis in CCl4-treated rats

Abstract

Liver damage and fibrosis are serious health problems without effective treatment. Proanthocyanidins (PAs) are flavonoids with several biological effects. We investigated the potential anti-fibrotic effect of proanthocyanidins on carbon tetrachloride (CCl4)-induced liver injury and fibrosis. Liver fibrosis was induced by oral administration of CCl4 three times a week for 5 and 9 weeks. PAs were daily administered in a dose of 500 mg/kg bw. Animals were divided into five groups: control groups, olive oil-treated group, Pas-treated group, CCl4-treated animals, and PAs + CCl4-treated rats. CCl4 and PAs were administered by gavage. Administration of CCl4 caused a significant elevation in alanine aminotransferase and aspartate aminotransferase activities, the concentration of alpha-2-macroglobulin, and bilirubin concentration. In addition, the protein and apolipoprotein contents were significantly decreased in the serum of CCl4-treated rats. These results were accompanied by histopathological alterations and increased inflammation, apoptosis, and DNA damage. Treatment with PAs caused remarkable regression of fibrosis and alpha-2-macroglobulin with improvement in histological characteristics of the liver after 5 and 9 weeks of intoxication. PAs could also maintain redox balance, evidenced by the prevention of lipid peroxidation and mitigation of the decrease in antioxidants. Treatment of intoxicated rats with PAs resulted in a significant decline in pro-inflammatory cytokines, including IL-6, IL-1β, and TNF-α in serum. This is associated with a remarkable decrease in apoptosis of hepatic cells shown by decreased levels of Bax, caspase-3, and -9, with increased Bcl-2. The protective effect of PAs was also evident by protecting DNA integrity in the intoxicated rats. PAs suppressed hepatic fibrosis, improved liver function and structure via modulating the interdependence between oxidative stress, inflammation, apoptosis, and DNA integrity in CCl4-treated rats.

Ameliorative Role of Psyllium Husk on Hepatotoxicity Induced by CCL4 in Male Albino Rats: A Histological and Immunohistochemical Study

“…Our study found that CCl4 increased the protein expression of the caspase-3 protein, showing that CCl4 can induce liver cell apoptosis. Our result agrees with (Deniz et al, 2019;Wang & Wu, 2019;Amer et al, 2022), who found that CCl4 increased caspase 3 activity, which indicates that apoptosis initiated the development of liver damage. Mitochondria are the main organelle that regulates apoptosis because they are the major site for producing energy and generating ROS.…”

The Hepatoprotective Effect of Two Date Palm Fruit Cultivars’ Extracts: Green Optimization of the Extraction Process

“…The outcomes of this study revealed that liver enzyme amplification is coupled with excessive lipid peroxidation and oxidative stress, as demonstrated by augmented MDA and diminished antioxidant enzymes. Lipid peroxidation-induced damage caused an upsurge in the hepatocytes’ cellular permeability with protein leakage, including aminotransferases, into serum, indicating hepatic injury and necrosis [ 56 ]. GSH is a vital protein thiol, which coordinates the body’s defense system against oxidative stress.…”

“…The inflammatory response has been reported as a critical process in CCl 4 -induced liver damage [ 56 ]. As previously described, CCl 4 -induced acute liver injury is closely associated with inflammation by elevating pro-inflammatory cytokine secretion [ 38 , 61 ].…”

Histological Evaluation of the Effect of Lactoferrin on Experimentally Induced Liver Fibrosis in Adult Male Albino Rat

“…The swollen mitochondria that were noticed in CCL4-treated group may be a sign of hepatocytes apoptosis. Amer et al [46] stated that mitochondria are the chief organelle that controls apoptosis because they are the main site for energy creation.…”