Dietary Beta-Hydroxy Beta-Methyl Butyrate Supplementation Alleviates Liver Injury in Lipopolysaccharide-Challenged Piglets

The current study was performed to investigate whether dietary β-hydroxy-β-methylbutyrate (HMB) could regulate liver injury in a lipopolysaccharide- (LPS-) challenged piglet model and to determine the mechanisms involved. Thirty piglets ( 21 ± 2 days old , 5.86 ± 0.18 kg body weight) were randomly divided into the control (a basal diet, saline injection), LPS (a basal diet), or LPS+HMB (a basal diet + 0.60% HMB-Ca) group. After 15 d of treatment with LPS and/or HMB, blood and liver samples were obtained. The results showed that in LPS-injected piglets, HMB supplementation ameliorated liver histomorphological abnormalities induced by LPS challenge. Compared to the control group, the activities of serum aspartate aminotransferase and alkaline phosphatase were increased in the LPS-injected piglets ( P < 0.05 ). The LPS challenge also downregulated the mRNA expression of L-PFK, ACO, L-CPT-1, ICDH β, and AMPKα1/2 and upregulated the mRNA expression of PCNA, caspase 3, TNF-α, TLR4, MyD88, NOD1, and NF-κB p65 ( P < 0.05 ). However, these adverse effects of the LPS challenge were reversed by HMB supplementation ( P < 0.05 ). These results indicate that HMB may exert protective effects against LPS-induced liver injury, and the underlying mechanisms might involve the improvement of hepatic energy metabolism via regulating AMPK signaling pathway and the reduction of liver inflammation via modulating TLR4 and NOD signaling pathways.

Download Full-text

Cinnamon Extract and Probiotic Supplementation Alleviate Copper-Induced Nephrotoxicity via Modulating Oxidative Stress, Inflammation, and Apoptosis in Broiler Chickens

Animals ◽

10.3390/ani11061609 ◽

2021 ◽

Vol 11 (6) ◽

pp. 1609

Author(s):

Sara T. Elazab ◽

Nahla S. Elshater ◽

Asmaa T. Y. Kishaway ◽

Huda A. EI-Emam

Keyword(s):

Mrna Expression ◽

Broiler Chickens ◽

Basal Diet ◽

Serum Levels ◽

Control Group ◽

Antioxidant Enzyme Activities ◽

Protective Effects ◽

Renal Protection ◽

Necrosis Factor Alpha ◽

Cinnamon Extract

The present study aimed to assess the potential protective effects of cinnamon (Cinnamomum zeylanicum, Cin) and probiotic against CuSO4-induced nephrotoxicity in broiler chickens. One-day-old Cobb chicks were assigned into seven groups (15 birds/group): control group, fed basal diet; Cin group, fed the basal diet mixed with Cin (200 mg/kg); PR group, receiving PR (1 g/4 L water); Cu group, fed the basal diets mixed with CuSO4 (300 mg/kg); Cu + Cin group; Cu + PR group; and Cu + Cin + PR group. All treatments were given daily for 6 weeks. Treatment of Cu-intoxicated chickens with Cin and/or PR reduced (p < 0.05) Cu contents in renal tissues and serum levels of urea, creatinine, and uric acid compared to the Cu group. Moreover, Cin and PR treatment decreased lipid peroxidation and increased antioxidant enzyme activities in chickens’ kidney. Additionally, significant reduction (p < 0.05) in the mRNA expression of tumor necrosis factor alpha (TNF-α), interleukin (IL-2) and Bax, and in cyclooxygenase (COX-II) enzyme expression, and significant elevation (p < 0.05) in mRNA expression of IL-10 and Bcl-2 were observed in kidneys of Cu + Cin, Cu + PR, and Cu + Cin + PR groups compared to Cu group. Conclusively, Cin and/or PR afford considerable renal protection against Cu-induced nephrotoxicity in chickens.

Download Full-text

DietaryN-acetylcysteine supplementation alleviates liver injury in lipopolysaccharide-challenged piglets

British Journal Of Nutrition ◽

10.1017/s0007114513002171 ◽

2013 ◽

Vol 111 (1) ◽

pp. 46-54 ◽

Cited By ~ 34

Author(s):

Dan Yi ◽

Yongqing Hou ◽

Lei Wang ◽

Binying Ding ◽

Zhengguo Yang ◽

...

Keyword(s):

Liver Injury ◽

Heat Shock Protein 70 ◽

Basal Diet ◽

Control Group ◽

Saline Injection ◽

Antioxidative Capacity ◽

Blood Samples ◽

Lps Challenge ◽

Tnf Α ◽

Pro Inflammatory Cytokines

The present study was carried out to determine whetherN-acetylcysteine (NAC) could modulate liver injury in a lipopolysaccharide (LPS)-challenged piglet model. For this purpose, eighteen piglets were randomly assigned to the control, LPS or NAC group. Piglets in the control and LPS groups were fed a basal diet, whereas those in the NAC group were fed the basal diet supplemented with 500 mg/kg NAC. On days 10, 13 and 20 of the trial, the LPS- and NAC-treated piglets were intraperitoneally administered LPS (100 μg/kg body weight), while the control group was administered the same volume of saline. On day 20 of the trial, blood samples were obtained 3 h after LPS or saline injection. On day 21, the piglets were killed to collect liver samples. Dietary NAC supplementation attenuated LPS-induced liver histomorphological abnormalities. Compared with the control group, in the LPS-challenged piglets, the activities of alanine aminotransferase and aspartate aminotransferase and the concentrations of H2O2, TNF-α, IL-6 and PGE2were dramatically increased in the plasma and the activity of superoxide dismutase in the plasma and that of glutathione peroxidase in the liver were significantly decreased. The LPS challenge also increased the concentration of AMP and the ratio of AMP:ATP, but decreased adenylate energy charges and the levels of ATP and ADP. These adverse effects of the LPS challenge were ameliorated by NAC supplementation. Moreover, NAC inhibited the LPS-induced increases in the abundance of liver heat shock protein 70 and NF-κB proteins. In conclusion, these results suggest that dietary NAC supplementation alleviates LPS-induced liver injury by reducing the secretion of pro-inflammatory cytokines, increasing the antioxidative capacity and improving energy metabolism.

Download Full-text

Vinpocetine attenuates fluoxetine-induced liver damage in rats; Role of Nrf2 and PPAR-γ

Human & Experimental Toxicology ◽

10.1177/09603271211051597 ◽

2021 ◽

pp. 096032712110515

Author(s):

Gellan Alaa Mohamed Kamel

Keyword(s):

Oxidative Stress ◽

Liver Injury ◽

Mrna Expression ◽

Liver Damage ◽

B Cell Lymphoma ◽

Control Group ◽

Related Factor ◽

Protective Effects ◽

Ppar Γ

Background Fluoxetine (FLX) has been widely used as first-line treatment in cases of depression and other neuropsychiatric disorders. Although its safety has been approved, the use of FLX was associated with liver injury and chronic liver disease. Vinpocetine (Vinpo), a nootropic drug, possesses antioxidant and anti-inflammatory effects. Objective This study aimed to evaluate the protective effects of Vinpo on FLX-induced liver damage pointing to the role of peroxisome proliferator-activated receptor-gamma (PPAR-γ) and nuclear factor erythroid 2-related factor 2 (Nrf2). Methods Rats were randomized to four groups: control group, Vinpo group (20 mg/kg/day; orally), FLX group (10 mg/kg/day; orally), and Vinpo + FLX group. Results FLX-induced liver damage was evidenced through elevated liver function biomarkers and induced hepatic histopathological changes. Concurrent Vinpo treatment resulted in a significant decrease in hepatotoxicity biomarkers and histopathological alterations. FLX-induced oxidative stress and inflammation were attenuated by Vinpo. In addition, Vinpo attenuated the hepatic NRF2 and HO-1 levels and up-regulated PPAR-γ expression. Moreover, FLX elevated Bcl-2-associated X protein (Bax) mRNA expression and decreased B-cell lymphoma 2 (Bcl2) mRNA expression were markedly reversed by Vinpo. Conclusion Vinpo possesses ameliorative effects against FLX-induced liver injury in rats. This effect may be due to attenuation of oxidative stress and inflammation, in addition to upregulation of PPAR-γ expression.

Download Full-text

Probucol Attenuates Cyclophosphamide-induced Oxidative Apoptosis, p53 and Bax Signal Expression in Rat Cardiac Tissues

Oxidative Medicine and Cellular Longevity ◽

10.4161/oxim.3.5.13107 ◽

2010 ◽

Vol 3 (5) ◽

pp. 308-316 ◽

Cited By ~ 57

Author(s):

Yousif A. Asiri

Keyword(s):

Superoxide Dismutase ◽

Glutathione Peroxidase ◽

Mrna Expression ◽

Corn Oil ◽

Lipid Lowering ◽

Control Group ◽

Albino Rats ◽

Protective Effects ◽

Antioxidant Genes ◽

Cardiac Tissues

Cyclophosphamide (CP) is a widely used drug in cancer chemotherapy and immunosuppression, which could cause toxicity of the normal cells due to its toxic metabolites. Probucol, a cholesterol-lowering drug, acts as potential inhibitor of DNA damage and shows to protect against doxorubicin-induced cardiomyopathy by enhancing the endogenous antioxidant system including glutathione peroxidase, catalase and superoxide dismutase. This study examined the possible protective effects of probucol, a lipid-lowering compound with strong antioxidant properties, against CPinduced cardiotoxicity. This objective could be achieved through studying the gene expression-based on the possible protective effects of probucol against CP-induced cardiac failure in rats. Adult male Wistar albino rats were assigned into four treatment groups: Animals in the first (control) and second (probucol) groups were injected intraperitoneally with corn oil and probucol (61 mg/kg/day), respectively, for two weeks. Animals in the third (CP) and fourth (probucol plus CP) groups were injected with the same doses of corn oil and probucol (61 mg/kg/day), respectively, for one week before and one week after a single dose of CP (200 mg/kg, I.P.). The p53, Bax, Bcl2 and oxidative genes signal expression were measured by real time PCR. CP-induced cardiotoxicity was clearly observed by a significant increase in serum creatine phosphokinase isoenzyme (CK-MB) (117%), lactate dehydrogenase (LDH) (64%), free (69%) and esterified cholesterol (42%) and triglyceride (69%) compared to control group. In cardiac tissues, CP significantly increases the mRNA expression levels of apoptotic genes, p53 with two-fold and Bax with 1.6-fold, and decreases the anti-apoptotic gene Bcl2 with 0.5-fold. Moreover, CP caused downregulation of antioxidant genes, glutathione peroxidase, catalase, and superoxide dismutase and increased the lipid peroxidation and decreased adenosine triphosphate (ATP) (40%) and ATP/ADP (44%) in cardiac tissues. Probucol pretreatment not only counteracted significantly the CP-induced increase in cardiac enzymes and apoptosis but also induced a significant increase in mRNA expression of antioxidant enzymes and improved ATP, ATP/ADP, glutathione (GSH) in cardiac tissues. In conclusion, data from the present study suggest that probucol prevents the development of CP-induced cardiotoxicity by a mechanism related, at least in part, to its ability to increase mRNA expression of antioxidant genes and to decrease apoptosis in cardiac tissues with the consequent improvement in mitochondrial oxidative phosphorylation and energy production.

Download Full-text

A Discovery of Relevant Hepatoprotective Effects and Underlying Mechanisms of Dietary Clostridium butyricum Against Corticosterone-Induced Liver Injury in Pekin Ducks

Microorganisms ◽

10.3390/microorganisms7090358 ◽

2019 ◽

Vol 7 (9) ◽

pp. 358 ◽

Cited By ~ 2

Author(s):

Yanhan Liu ◽

Cun Liu ◽

Liqing Huang ◽

Zhaofei Xia

Keyword(s):

Oxidative Stress ◽

Lipid Metabolism ◽

Liver Injury ◽

Signaling Pathway ◽

Basal Diet ◽

Clostridium Butyricum ◽

Pekin Ducks ◽

Injury Model ◽

Hepatoprotective Effects ◽

Underlying Mechanisms

Clostridium butyricum (C. butyricum) can attenuate oxidative stress, inflammation, and hepatic fatty deposition in poultry, however, the underlying mechanisms for this in Pekin ducks remain unclear. This study evaluated these hepatoprotective effects and the underlying mechanisms in a corticosterone (CORT)-induced liver injury model in Pekin ducks fed a C. butyricum intervention diet. A total of 500 Pekin ducks were randomly divided into five groups: one group (CON group) was only provided with a basal diet, three groups were provided a basal diet with 200 mg/kg (LCB group), 400 mg/kg (MCB group), or 600 mg/kg (HCB group) C. butyricum, respectively, and one group was provided a basal diet with 150 mg/kg aureomycin (ANT group) for 42 d. At 37 days-old, all ducks received daily intraperitoneal injections of CORT for five days to establish a liver injury model. C. butyricum intervention alleviated liver injury by decreasing the liver organ indices, hepatic steatosis and hepatocyte necrosis, and improving liver function, antioxidant capacity, and inflammatory factors. Hepatic RNA-seq revealed 365 differentially expressed genes (DEGs) between the MCB and CON groups, with 229 up- and 136 down-regulated DEGs in the MCB group. Between the MCB and ANT groups, 407 DEGs were identified, including 299 up- and 108 down-regulated genes in MCB group. Some DEGs in the MCB group related to oxidative stress and inflammatory responses such as Sod3, Tlr2a/b, and Il10, which were up-regulated, while Apoa1, Cyp7a1, Acsl1/5, Fasn, Ppar-γ, and Scd, which are involved in lipid metabolism, were down-regulated, indicating that these genes were responsive to dietary C. butyricum for the alleviation of corticosterone-induced hepatic injury. Toll-like receptor signaling, PI3K-Akt signaling pathway, cytokine-cytokine receptor interaction, peroxisome proliferator-activated receptor (PPAR) signaling pathway, adipocytokine and glycerophospholipid metabolism signaling pathway were significantly enriched in the MCB group. These findings indicate that C. butyricum intervention can protect Pekin ducks from corticosterone-induced liver injury by the modulation of immunoregulatory- and lipid metabolism-related genes and pathways.

Download Full-text

Dietary fish oil supplementation alters liver gene expressions to protect against LPS-induced liver injury in weanling piglets

Innate Immunity ◽

10.1177/1753425918821420 ◽

2019 ◽

Vol 25 (1) ◽

pp. 60-72 ◽

Cited By ~ 1

Author(s):

Jing Zhang ◽

Xin Xu ◽

Huiling Zhu ◽

Yang Wang ◽

Yongqing Hou ◽

...

Keyword(s):

Liver Injury ◽

Fish Oil ◽

Rna Sequencing ◽

Corn Oil ◽

Sequencing Analysis ◽

Protective Effects ◽

Gene Expressions ◽

Inflammatory Genes ◽

Lps Challenge ◽

Fish Oil Supplementation

Here, the potential mechanisms of the protective effects of fish oil against LPS-induced liver injury in a piglet model were investigated by using RNA sequencing. Twenty-four piglets were used in a 2 × 2 factorial design, and the main factors included diet (5% corn oil or 5% fish oil) and immunological challenge (LPS or saline, on d 19). All piglets were slaughtered at 4 h after challenge, and liver samples were collected. Fish oil improved liver morphology and reduced TNF-α, IL-1β and IL-6 productions after LPS challenge. RNA sequencing analysis showed fish oil had significant effect on the expressions of genes involved in immune response during LPS-induced inflammation. Selected gene expression changes were validated using quantitative RT-PCR. Fish oil reduced the expressions of pro-inflammatory genes IL1R1, IL1RAP, CEBPB and CRP, and increased that of anti-inflammatory genes IL-18BP, NFKBIA, IFIT1, IFIT2 and ATF3. Moreover, fish oil restored the expressions of some lipid metabolism-related genes, such as ACAA1, ACACA, ACADS and ACADM, which were only decreased in pigs fed a corn oil diet after LPS challenge. Our RNA sequencing reveals novel gene-nutrient interactions following fish oil supplementation and evoked inflammation, which add to the current understanding of the benefits of n-3 polyunsaturated fatty acids against liver injury.

Download Full-text

Hepatoprotective Activity of Reduohanxiao-tang (Yuldahanso-tang) is Related to the Inhibition of β-Glucuronidase

The American Journal of Chinese Medicine ◽

10.1142/s0192415x03000722 ◽

2003 ◽

Vol 31 (01) ◽

pp. 111-117 ◽

Cited By ~ 9

Author(s):

Hyung-Sup Bae ◽

Young-Suk Kim ◽

Ki-Ho Cho ◽

Kyung-Sup Lee ◽

Jung-Jin Kim ◽

...

Keyword(s):

Liver Injury ◽

Liver Diseases ◽

Herbal Medicines ◽

Intestinal Bacteria ◽

Hepatoprotective Activity ◽

Control Group ◽

Human Intestinal Bacteria ◽

Serum Aspartate Aminotransferase ◽

Hepatoprotective Effects ◽

Main Component

β-Glucuronidase-inhibitory and hepatoprotective effects of Reduohanxiao-tang (Yuldahanso-tang), which has been used for liver diseases and stroke, on carbon tetrachloride (CCl4)-induced hepatotoxicity of rats were investigated. Reduohanxiao-tang potently inhibited β-glucuronidases. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactic acid dehydrogenase (LDH) levels of the CCl4 group orally treated with Reduohanxiao-tang (100 mg/kg) were lowered to 54%, 71.5% and 66.1% of the CCl4-treated control group, respectively. Among the ingredients of the Reduohanxiao-tang, the rhizomes of Pueraria thunbergiana and it Scutellaria baicalensis potently inhibited β-glucuronidases and protected against CCl4-induced liver injury. Orally administered puerarin, which is a main component of Pueraria thunbergiana, showed potent hepatoprotective activity, but did not inhibit β-glucuronidase. However, daidzein, which is produced from puerarin by human intestinal bacteria, potently inhibited β-glucuronidase. These results suggest that β-glucuronidase inhibition by herbal medicines may protect a gainst CCl4-induced liver injury.

Download Full-text

Effects of clinoptilolite (zeolite) on attenuation of lipopolysaccharide-induced stress, growth and immune response in broiler chickens

Annals of Animal Science ◽

10.1515/aoas-2015-0010 ◽

2015 ◽

Vol 15 (3) ◽

pp. 681-697 ◽

Cited By ~ 7

Author(s):

Qiu Jue Wu ◽

Qin Yu Wang ◽

Tian Wang ◽

Yan Min Zhou

Keyword(s):

Growth Performance ◽

Broiler Chickens ◽

Intestinal Morphology ◽

Control Group ◽

Protective Effects ◽

Gut Health ◽

Ileal Mucosa ◽

Sod Activity ◽

Lps Challenge ◽

Natural Clinoptilolite

Abstract The effects of natural clinoptilolite (NCLI) and modified clinoptilolite (MCLI) were evaluated in broilers challenged with lipopolysaccharide (LPS) in a 21-d feeding trial. A total of 288 one-day-old chickens were allocated into three treatment groups: control, NCLI (2%) and MCLI (2%). Half of the birds from each treatment group were challenged with either 0.9% NaCl solution or LPS (250 μg/kg body weight, orally administered) at 16, 18 and 21 d of age. Before the LPS challenge, no dietary effect on bird growth performance was found (P>0.05). When LPS was orally administered, no significant changes in growth performance of broilers was found (P>0.05). However, small intestinal morphology and development, malondialdehyde (MDA) content of the jejunual and ileal mucosa, and superoxide dismutase (SOD) activity of the ileal mucosa were significantly affected (P<0.05). Supplementation with NCLI and MCLI significantly decreased the MDA contents of the jejunual and ileal mucosa and improved the SOD activity of the ileal mucosa and the development of the small intestine compared with the control group (P<0.05). The results indicated that NCLI and MCLI additions in feed had protective effects on the gut health of broilers against LPS challenge.

Download Full-text

Genipin and Insulin Combined Treatment Improves Implant Osseointegration in Type 2 Diabetic Rats

10.21203/rs.3.rs-103704/v1 ◽

2020 ◽

Author(s):

Jiajia Zhang ◽

Ya-nan Wang ◽

Tingting Jia ◽

Haiyun Huang ◽

Dongjiao Zhang ◽

...

Keyword(s):

Oxidative Stress ◽

Combined Treatment ◽

Harmful Effect ◽

Diabetic Rats ◽

Control Group ◽

Ampk Signaling ◽

Glucose Levels ◽

Negative Effect ◽

Underlying Mechanisms

Abstract Background: Type 2 diabetes mellitus (T2DM) has a harmful effect on the stability and osseointegration of dental implants. T2DM induces mitochondrial damage by inhibiting AMPK signaling, resulting in oxidative stress and poor osteogenesis in the peri-implant bone area. Genipin is a major component of gardenia fruits with strong antioxidant, anti-inflammation, and anti-diabetic actions, and it also can activate mitochondrial quality control via the AMPK pathway. The purpose of this study was to investigate the effects of genipin and insulin treatment on implant osseointegration in T2DM rats and explore the underlying mechanisms. Methods: Streptozotocin-induced diabetic rats received implant surgery in their femurs, and were then assigned to five groups that were subjected to different treatments for three months: control group, T2DM group, insulin-treated T2DM group (10 IU/kg), genipin-treated T2DM group (50 mg/kg), and the genipin and insulin combination-treated T2DM group. Then, we regularly assessed the weight and glucose levels of the animals. Rats were euthanized at three months after the implantation procedure, and the femora were harvested for microscopic computerized tomography analysis, biomechanical tests, and different histomorphometric assessment. Results: The results indicated that the highest blood glucose and oxidative stress levels were measured for the T2DM group, resulting in the poorest osseointegration. The combination-treated T2DM group mitigated hyperglycemia and normalized, reactivated AMPK signaling, and alleviated oxidative stress as well as reversed the negative effect of osseointegration. There were beneficial changes observed in the T2DM-genipin and T2DM-insulin groups, but these were less in comparison to the combination treatment group. Conclusion: Our study suggests that treatment with genipin in combination with insulin could be an effective method for promoting implant osseointegration in T2DM rats, which may be related to AMPK signaling.

Download Full-text

Combined Water Extracts from Oxidation-Treated Leaves and Branches of Hovenia dulcis Has Anti-Hangover and Liver Protective Effects in Binge Alcohol Intake of Male Mice

Nutrients ◽

10.3390/nu13124404 ◽

2021 ◽

Vol 13 (12) ◽

pp. 4404

Author(s):

Jihyun Je ◽

Miyoung Song ◽

Ji Hyeong Baek ◽

Jae Soon Kang ◽

Hye Jin Chung ◽

...

Keyword(s):

Liver Injury ◽

Traditional Medicine ◽

Alcohol Intake ◽

Protective Effects ◽

Male Mice ◽

Protective Properties ◽

Water Extracts ◽

Underlying Mechanisms ◽

Dried Extract ◽

Hovenia Dulcis

Hovenia dulcis, known as the oriental raisin tree, is used for food supplements and traditional medicine for the liver after alcohol-related symptoms. However, little information exists about the use of its leaves and branches. In this study, we established a method to use the leaves and branches to develop anti-hangover treatment and elucidated the underlying mechanisms. Oxidation-treated leaves (OL) exhibited high antioxidant content comparable to that of the peduncles and showed an anti-hangover effect in male mice. The branch extract (BE) was enriched in the flavonoid catechin, approximately five times more than OL extract. The mixture of OL and BE (OLB) was formulated in a 2:1 ratio with frozen-dried extract weight and was tested for anti-hangover effects and protective properties against binge alcohol-induced liver injury. OLB showed better anti-hangover effect than OL. In addition to this anti-hangover effect, OLB protected the liver from oxidative/nitrosative damage induced by binge alcohol intake.

Download Full-text