Hepatopoietin Cn (HPPCn) Generates Protective Effects on Acute Liver Injury

Abstract

Objective: To observe the protective role of hapatopoietin Cn (HPPcn) on acute liver injury. Methods: Six hours after 10 mmol/L CCl 4 , 150 mmol/L ethanol, or 0.6 mmol/L H 2 O 2 treatment, SMMC7721 human hepatoma cells were incubated with 10, 100, or 200 ng/ml recombinant human HPPCn protein (rhHPPCn) for an additional 24 h. The cell survival rate was analyzed using the CCK-8 assay. The CCl 4 -induced apoptosis of SMMC7721 cells was detected by flow cytometry. Then, the levels of glutamic oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), malondialdehyde (MDA), lactate dehydrogenase (LDH), glutathione peroxidase (GSH-PX), and superoxide dismutase (SOD) in SMMC7721 cell lysates and cell culture supernatant were detected. SMMC7721 cells were treated with different concentrations of rhHPPCn (0, 10, and 100 ng/ml). The cell proliferation indexes (BrdU incorporation and PCNA expression) were detected by immunohistochemistry (IHC). An acute liver injury mouse model was established by a one-time intraperitoneal injection of 20% CCl 4 at a volume of 5 ml/kg body weight. One hour after CCl 4 injection, 1.25 or 2.5 mg rhHPPCn/12 h/kg body weight was injected via the tail vein. The serum levels of GOT and GPT were detected at different time points. Pathological changes in the liver were evaluated. PCNA expression levels were observed by IHC. Results: rhHPPCn increased the survival rate of SMMC7721 cells and inhibited chemical toxicity-induced cell apoptosis. The levels of GOT, GPT, MDA, and LDH in the cell supernatant were significantly reduced, while GSH-PX and SOD were significantly increased after rhHPPCn treatment in the CCl 4 -treated SMMC7721 cells. BrdU incorporation and PCNA expression increased in a concentration-dependent manner, indicating that rhHPPCn promotes cell proliferation. The results showed that rhHPPCn significantly reduced the serum levels of GOT and GPT in CCl 4 -induced acute liver injury mice. rhHPPCn alleviated the tissue damage and increased PCNA expression, indicating the promotion of proliferation after acute injury. Conclusion: rhHPPCn protects hepatocytes from chemical toxins by promoting proliferation and inhibiting apoptosis in vivo and in vitro . Our study provides new insights for the clinical treatment of acute liver injury.

The Protective Effects of Zornia diphylla (L.) Pers. Against Acute Liver Injury Induced by Carbon Tetrachloride in Mice

“…However, the content of MDA decreased significantly and the activities of SOD, GSH and CAT increased significantly in the liver tissue of mice in the ZDP groups, suggesting that ZDP has a certain antioxidant effect and can effectively improve the ability of cells to scavenge free radicals and reduce the damage to hepatocytes under free radical attack, which may be related to the antioxidant effect. These results were consistent with those of previous research (Li et al, 2019;Ren et al, 2019). IL-1β, IL-6, TNF-α and other inflammatory factors play an important role in the inflammatory process of acute tissue injury (Chalasani et al, 2008).…”

“…Changes in body mass and liver index can reflect the degree of liver injury ( Li et al, 2019 ). As shown in Figure 3 , CCl 4 significantly reduced the body mass of mice ( p < 0.01).…”

Mechanism of hydroxysafflor yellow A on acute liver injury based on transcriptomics

“…Weight loss and liver index increase might indicate liver damage (Li et al, 2019). As observed in Figure 2, relative to the control group, in the model group, the body mass of rats was dramatically decreased (p < 0.05).…”

“…Moreover, these ROS are capable of attacking fatty acids and causing peroxidation (Li et al, 2019). As the metabolic endproduct of lipid peroxides, MDA can aggravate cell membrane damage by destroying the function, structure, and metabolism of biofilms (Lixin et al, 2019).…”

Hepatoprotective and antioxidant effects of alcesefoliside from Astragalus monspessulanus

“…There are many studies reporting the key role of the oxidative stress in the hepatic injury, induced by CCl 4 . It has been found that chlorinated free radicals, formed via cytochrome P450 bio activation of CCl 4 , such as trichloromethyl (•CCl 3 ) and trichloromethyl peroxyl (•OOCCl 3 ) radicals, impair the hepatocytes, inducing morphological changes in the endoplasmic reticulum, Golgi apparatus, plasma membrane, and mitochondria of the targeted cells, leading to apoptosis (Li et al, 2019). Membrane disintegration of hepatocytes results in subsequent release of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and γ-glutamyltransferase (GGT) as well as decreased endogenous antioxidant defence system (Singh et al, 2008;Simeonova et al, 2014).…”