Chlorogenic Acid Alleviated Liver Dysfunction Through Activating PINK1/Parkin Dependent Mitophagy

Background: Chlorogenic acid (CGA) is a natural polyphenolic compound with anti-inflammatory, antioxidant effects. It could improve mitochondrial dysfunction that was a key feature of acetaminophen (APAP) -induced liver injury. This study aimed to identify whether promoting mitophagy was associated with the hepatocyte protection for CGA.Methods: Acute hepatic injury model was induced by APAP in mice after CGA administration for 14 days. Survival rate was recoded within 24h of modeling. Serum aminotransferase, hepatic histopathology and TUNEL assays were simultaneously performed. The expression of apoptosis-related proteins (Bax and Bcl-2) and mitophagy-related genes and proteins (LC3Ⅱ, P62, PINK1 and Parkin) were analyzed. The fluorescence co-localization of LC3Ⅱ and Tom20 was analyzed with immunofluorescence.Results: Compared with APAP group, CGA pretreatment significantly increased survival rate of APAP-induced mice, inhibited the activity of ALT, AST and LDH in serum, and alleviated pathological features of liver such as inflammatory cell infiltration, necrosis of liver cells and vacuolation (p<0.05). Moreover, our data from the TUNEL and western blotting analysis showed that CGA significantly decreased the number of apoptotic cells and reversed the elevated Bax level and decreased Bcl-2 level(p<0.05). Furthermore, we found that CGA promoted the fluorescence co-localization of LC3Ⅱ and Tom20 and enhanced the protein expression of LC3Ⅱ (p<0.05). Finally, CGA significantly promoted mitophagy by exhibiting the increased gene and protein expression of PINK1 and Parkin.Conclusions: Our results demonstrated that CGA promoted PINK1/Parkin dependent mitophagy and inhibited hepatic apoptosis to exert protection against liver damage in APAP-induced mice.

Pharmacological Evaluation of Novel 1,2,4-triazine Derivatives Containing Thiazole Ring Against Hepatocellular Carcinoma

Background: New 6-hydroxy-5-(p-hydroxybenzylidene)-3-phenyl-2-[(5-p-chlorophenyl)-1,3-thiazol-2-yl]-1, 2, 4-triazine derivatives containing a thiazole ring were synthesised as potential antitumor agents. Methods: Cytotoxicity of compounds (3) and (4) were evaluated in human hepatocellular carcinoma (HCC) cell lines (HepG2); compound (3) showed more cytotoxicity (IC50=9.0μg/ml) than compound (4) (IC50=18.40μg/ml) using doxorubicin as standard. The degree of toxicity of compound (3) was assessed by the LD50 with its anticancer performance by suppressing tumor angiogenesis against diethyl nitrosamine (DENA) induced hepatocellular carcinoma (HCC) in male rat model. Results : Carcinogenic rats showed a significant increase in markers of angiogenesis, tumour growth, and liver function tests and malondialdehyde level coupled by reduced hepatic glutathione level and caspase-3 activity. The distribution of compound (3) to animals after the development of HCC improved biochemical alterations from a DENA chemical carcinogen that is confirmed by hepatic histopathology. Conclusion: Compound 3 perhaps utilized as a strong applicant for newly therapeutic protocols against hepatocarcinogenesis by controlling tumor angiogenesis and renovating the activity of hepatic marker enzymes in addition reversing the oxidant-antioxidant imbalance in corporation with amelioration of histopathology. While the trial supports the use of compound 3 for improved HCC outcome and the toxicity and side effect should be considered.

Effect of Nanosilica and Bentonite as Mycotoxins Adsorbent Agent in Broiler Chickens’ Diet on Growth Performance and Hepatic Histopathology

Mycotoxins are toxic secondary metabolites produced by different strains of fungi, such as aspergillus, fusarium, and penicillium that can contaminate feed ingredients or the entire feed of poultry and animals. Mycotoxins can cause many serious complications to both humans and animals due to carcinogenic, mutagenic, and immunosuppressive disorders. Therefore, the present experiment aims to investigate the effect of broiler chickens’ diets supplemented with different levels of nanosilica (NS) as an adsorbent agent of mycotoxins on their growth performance and hepatic histopathology. Detectable levels of toxins were present in the feed before feeding, and all levels of mycotoxins were above the normal limit. A total of 180 one-day-old male Arbor Acres broiler chickens were allocated randomly to six treatment groups with three replicates per group, including ten chickens per replicate. The experiment lasted for five weeks, and dietary treatments included control diet and diets with four levels of nanosilica as 0.05%, 0.10%, 0.15%, and 0.20% as well as 0.50% bentonite (fixfin® Dry) diet. Bodyweight, body weight gain, average daily feed intake, and feed conversion ratio were measured weekly. At the end of the fifth week, six chickens per treatment were sacrificed to investigate the effects of NS and bentonite on carcass characteristics and hepatic histopathology. The results showed that providing broiler chickens’ diets with an adsorbent agent, such as NS or bentonite, can reduce the side effects of mycotoxins and enhance their growth performance. The best record was achieved with NS at 0.20%, compared with the control group and other dietary treatment groups. Accordingly, 0.20% of NS could be used in broiler chickens’ diets to minimize the harmful effects of mycotoxins.

Hepatic Histopathology Among Excessive Drinkers Without Advanced Liver Disease

AimsAlcohol-associated liver disease represents a spectrum of histopathological changes from steatosis to advanced fibrosis and cirrhosis. The major goals of this retrospective study were to characterize the histologic features in patients with excessive alcohol use who presented with an abnormal hepatic panel and/or abnormal radiographic imaging and did not meet the clinical diagnosis of alcoholic hepatitis or cirrhosis.MethodsWe performed a retrospective study to describe hepatic histology of 62 and 83 excessive drinkers with normal and abnormal serum aspartate transaminase, respectively. The types of inflammatory cells in the liver were characterized by immunohistochemistry for CD4, CD8, CD20, CD68 and myeloperoxidase.ResultsAmong 62 patients with aspartate aminotransferase (AST) ≤ 50 U/L, 37% had histological evidence of steatosis. Of these, we found evidence of hepatocyte ballooning (21%), lobular inflammation (50%), portal inflammation (52%) and fibrosis (14%). For those with AST &gt; 50 U/L, the presence of hepatic steatosis, lobular inflammation and portal inflammation was observed in 29, 60 and 69% of patients, respectively. Fibrosis was found in 33%, four with bridging fibrosis, and one with cirrhosis. We observed the aggregation of CD68+ macrophages, rather than normally distributed with minimal neutrophilic infiltration. Lobular and portal lymphocytic infiltrations are primarily CD8+ T cells.ConclusionAbnormal hepatic histopathology occurs in excessive drinkers with normal transaminase activity. Future studies to determine the diagnostic modalities to detect such abnormalities and to better understand its clinical implications and long-term outcome are needed.

THE EFFECT OF AMORPHOPHALLUS MUELLERI BLUME AND MORINGA OLEIFERA L LEAVES ON BODY WEIGHT, FEED INTAKE, AND HEPATIC HISTOPATHOLOGY IN MICE

Objective: This study aims to determine the effect of Amorphophallus muelleri Blume and Moringa oleifera L leaf on body weight, food intake, and hepatic histopathology in mice. Methods: The mice were divided into five groups according to their diet, which includes porang, wheat, porang-moringa, wheat-moringa, and control diet. Each group consists of 5 males and 5 females, which were fed for 28 d, and then analyzed for their body weight, total food intake, alanine aminotransferase (ALT) as well as aspartate aminotransferase (AST) levels in plasma, and hepatic histopathology. Results: The result showed that the group of porang and porang-moringa has lower body weight and feed intake, which is significantly different compared to the others. Furthermore, an increase was observed on plasma AST/ALT activities in 30% porang and 20% porang-moringa group. Also, one of the mice of porang group has inflammatory cell infiltration (++) on histopathology results. Conclusion: It was therefore concluded that feeding containing porang causes low food consumption. Furthermore, weight loss increases AST/ALT and leukocyte infiltration even though a mouse consistently deteriorates.

Phytochemical analysis and hepatoprotective activity of Raphanus sativus var. sativus in Sprague-Dawley rats

Purpose: To determine the phenolic and flavonoid contents of R. sativus rhizome ethanol extract and the hepatoprotective effect of the extract in rats. Methods: Folin–Ciocalteau and aluminum chloride colorimetric tests were used to determine the contents of phenols and flavonoids in the R. sativus extract. Male Sprague-Dawley rats induced with CCl4 to develop hepatotoxicity were treated orally with R. sativus extract for 4 weeks. The antioxidant and anti-inflammatory effects of the extract on the liver were determined by evaluating the concentration of oxidative analytes, serum liver enzymes and lipids, and hepatic histopathology and cytochrome P450 2E1 expression. Results: R. sativus extract significantly (p < 0.05) reduced the hepatotoxic effect of CCl4 via its antioxidant activities and protection of liver tissues from oxidative damage. Conclusion: The hepatoprotective effects of R. sativus rhizome ethanol extract are attributed to its highphenolic and flavonoid contents. Keywords: R. savitus rhizome, Phenols, Flavonoid contents, antioxidant, Hepatoprotective

Hydroalcoholic Extract of Iranian Caper Leaves Protects Hepatic Toxicity by Suppressing Oxidative Stress in Mice

Capparis spinosa L. (caper) is an aromatic plant, commonly used in the Mediterranean diet, possessing numerous antioxidant compounds, such as phenols, rutin, tocopherols, carotenoids, and vitamin C in its leaves. Thus, the present study investigated the effects of Iranian caper leaves extract on oxidative stress caused by CCl4 in the mice’s liver. This study was conducted on 42 male mice in seven groups. The control group, the sham group, the CCl4 group, the Iranian caper leaves extract 100, 200, and 400 mg/kg + CCl4 groups. Then, Biochemicals, oxidative stress, and hepatic histopathology parameters were evaluated. The co-administration of Iranian caper leaves extract, and CCl4 significantly decreased the levels of aspartate aminotransferase, alanine aminotransferase, and reactive oxygen species, malondialdehyde (P<0.001) and significantly increased the levels of glutathione and catalase in comparison with the group treated with CCl4 alone (P<0.01).Furthermore, Iranian caper leaves extract improved histopathological changes such as the the inflammation and necrosis of hepatocytes. Iranian caper leaves extract has protective effects on hepatotoxicity induced by CCl4, mainly through suppressing oxidative stress.