Abstract
Hepatitis is an inflammatory disease of the liver and is considered one of the leading causes of death worldwide. Due to its scavenging activity, Punica granatum may be used for the treatment and prevention of liver diseases. The current study investigated the protective mechanism underlying the effects of pomegranate against a rat model of carbon tetrachloride–induced liver injury. Intraperitoneal injection of CCl4 resulted in liver inflammation, oxidative stress, and accumulation of lipid in hepatocytes. CCl4 induced a downregulation of superoxide dismutase (SOD), glutathione (GSH), and melonaldehyde (MDA). Pomegranate protection was assessed in terms of biochemical parameters, histopathology, and immunohistochemistry. Promegranate administration decreased inflammation, elevated serum enzymes and ROS production, and countered the debilitating effects caused by CCl4. In addition, CCl4-induced histological changes were absent in the crude pomegranate extract group, which also enhanced the scavenging activity of reactive oxygen species by enhancing the antioxidant defense mechanism as confirmed by detecting MDA, SOD, and GSH expressions. The migration of CD68+ macrophages was halted at the injured area of the central vein and the number of macrophages was reduced to the normal control by the crude extract compared to the positive control silymarin group. Likewise, protective effects of ethylacetate and the aqueous fraction of the crude extract were also observed. However, the butanol and n-hexane fractions displayed increased levels of ALT, AST, and ALP as compared to silymarin. About 25% damage to hepatocytes was observed in the butanol and n-hexane group by histopathological examination, which is a little better compared to the CCl4-treated group. The crude extract and its ethyl acetate and aqueous fractions may be accountable for the hepatoprotective potential of Punica granatum, which was further confirmed by in vivo experiments. Together, these findings confirm that pomegranate exerts hepatoprotective activity against CCl4-induced oxidative stress and liver damage.
Highlights
Liver diseases are one of the most serious health issues in the world
Liver sections of the normal control group exhibited typical lobular architecture, with a central vein fenced by the hepatic cord of cells with clear spaces lined by elongated endothelial and Kupffer cells (Table 1; Figures 2A,B)
The CCl4treated group revealed loss of hepatic architecture with clear pale areas having degenerated and necrotic hepatocytes and the presence of inflammatory cells around the central vein with distinct nuclei (Table 1). This pointed toward the fact that the injurious free radical CCl3− is generated only in the hepatocytes
Summary
The liver is concerned with metabolism and detoxification of exogenous substances such as drugs, toxic chemicals, and viruses and is very prone to injury (Moore et al, 2010; Moore et al, 2013). Toxic chemicals are the most serious cause of liver injury, mediated by the free radical–induced oxidative stress (Rechnagel et al, 1973). Carbon tetrachloride (CCl4) is one of the toxic xenobiotics widely used in animal models to induce oxidative stress–mediated hepatitis (Pierce et al, 1987), resulting in apoptosis, inflammation, and fibrosis (Wong et al, 1998). The main mechanism through which CCl4 induces hepatotoxicity is the generation of free radicals (Qureshi et al, 2009). The free radical sequentially attacks the hepatocyte cell membrane, leading to lipid peroxidation and cell death. CCl4 intoxication triggers the production of proinflammatory cytokines such as TNF-α, TGF-β, and IL-6, stimulating inflammatory cell recruitment at the site of injury (Sun et al, 2001)
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