Synergistic effect of Aminoguanidine and L-Carnosine against Thioacetamide-induced Hepatic Encephalopathy in rats: Behavioral, Biochemical and Ultra Structural Evidences

2020 ◽  
Author(s):  
Nehal Aly Afifi ◽  
Amer Ramadan ◽  
Emad Erian ◽  
Ahmed A. Sedik ◽  
Mohamed M. Amin ◽  
...  
Keyword(s):  
Hepatic Encephalopathy ◽  
Synergistic Effect ◽  
Hepatic Necrosis ◽  
Histopathological Analysis ◽  
Related Factor ◽  
Oxidative Stress Biomarkers ◽  
Ultrastructural Studies ◽  
Chronic Hepatic Injury ◽  
Locomotor Impairment ◽  
Neurological Alterations

Hepatic encephalopathy (HE) depicts the cluster of neurological alterations that occur during acute or chronic hepatic injury. This study was aimed to evaluate the possible synergistic effect between aminoguanidine (AG; 100 mg/kg; p.o.) and l-carnosine (CAR; 100 mg/kg; p.o.) on HE that was induced by thioacetamide (TAA; 100 mg/kg; i.p) thrice weekly for six weeks. Twenty-four hours after the last treatment; behavioral changes, biochemical parameters, histopathological analysis, immunohistochemical and ultrastructural studies were conducted. Combining AG with CAR improved TAA-induced locomotor impairment and motor incoordination evidenced by; reduced locomotor activity and decline in motor skill performance as well as ameliorated cognitive deficits. Moreover, both drugs restored the levels of serum hepatic enzymes as well as serum and brain levels of ammonia. In addition to, the combination significantly modulated hepatic and brain oxidative stress biomarkers, inflammatory cytokines and cleaved caspase-3 expression. Furthermore, they succeeded to activate nuclear erythroid 2-related factor 2 (Nrf2) expression and ameliorate markers of HE including hepatic necrosis and brain astrocyte swelling. This study depicts that combining AG with CAR exerted new intervention for hepatic and brain damage in HE due to their complementary antioxidant, anti-inflammatory effect and hypoammonemic effects via Nrf2/HO-1 activation and NO inhibition.

scholarly journals Nrf2 Activation Attenuates Acrylamide-Induced Neuropathy in Mice

2021 ◽  
Vol 22 (11) ◽  
pp. 5995
Author(s):  
Chand Basha Davuljigari ◽  
Frederick Adams Ekuban ◽  
Cai Zong ◽  
Alzahraa A. M. Fergany ◽  
Kota Morikawa ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
Messenger Rna ◽  
Hepatic Necrosis ◽  
Related Factor ◽  
Necrosis Factor Alpha ◽  
Adult Mice ◽  
Nrf2 Signaling Pathway ◽  
Antioxidant Proteins ◽  
Oxide Synthase

Acrylamide is a well characterized neurotoxicant known to cause neuropathy and encephalopathy in humans and experimental animals. To investigate the role of nuclear factor erythroid 2-related factor 2 (Nrf2) in acrylamide-induced neuropathy, male C57Bl/6JJcl adult mice were exposed to acrylamide at 0, 200 or 300 ppm in drinking water and co-administered with subcutaneous injections of sulforaphane, a known activator of the Nrf2 signaling pathway at 0 or 25 mg/kg body weight daily for 4 weeks. Assessments for neurotoxicity, hepatotoxicity, oxidative stress as well as messenger RNA-expression analysis for Nrf2-antioxidant and pro-inflammatory cytokine genes were conducted. Relative to mice exposed only to acrylamide, co-administration of sulforaphane protected against acrylamide-induced neurotoxic effects such as increase in landing foot spread or decrease in density of noradrenergic axons as well as hepatic necrosis and hemorrhage. Moreover, co-administration of sulforaphane enhanced acrylamide-induced mRNA upregulation of Nrf2 and its downstream antioxidant proteins and suppressed acrylamide-induced mRNA upregulation of tumor necrosis factor alpha (TNF-α) and inducible nitric oxide synthase (iNOS) in the cerebral cortex. The results demonstrate that activation of the Nrf2 signaling pathway by co-treatment of sulforaphane provides protection against acrylamide-induced neurotoxicity through suppression of oxidative stress and inflammation. Nrf2 remains an important target for the strategic prevention of acrylamide-induced neurotoxicity.

scholarly journals Lemon Balm and Dandelion Leaf Extracts Synergistically Protect against Carbon Tetrachloride-Induced Acute Liver Injury in Mice

2021 ◽  
Vol 11 (1) ◽  
pp. 390
Author(s):  
Beom-Rak Choi ◽  
Il-Je Cho ◽  
Su-Jin Jung ◽  
Jae-Kwang Kim ◽  
Dae-Geon Lee ◽  
...  
Keyword(s):  
Carbon Tetrachloride ◽  
Liver Injury ◽  
Acute Liver Injury ◽  
Antioxidant Activities ◽  
Body Weight Gain ◽  
Histopathological Analysis ◽  
Related Factor ◽  
Mrna Levels ◽  
Protective Effects ◽  
Lemon Balm

Lemon balm and dandelion are commonly used medicinal herbs exhibiting numerous pharmacological activities that are beneficial for human health. In this study, we explored the protective effects of a 2:1 (w/w) mixture of lemon balm and dandelion extracts (MLD) on carbon tetrachloride (CCl4)-induced acute liver injury in mice. CCl4 (0.5 mL/kg; i.p.) injection inhibited body weight gain and increased relative liver weight. Pre-administration of MLD (50–200 mg/kg) for 7 days prevented these CCl4-mediated changes. In addition, histopathological analysis revealed that MLD synergistically alleviated CCl4-mediated hepatocyte degeneration and infiltration of inflammatory cells. MLD decreased serum aspartate aminotransferase and alanine transferase activities and reduced the number of liver cells that stained positive for cleaved caspase-3 and cleaved poly(ADP-ribose) polymerase, suggesting that MLD protects against CCl4-induced hepatic damage via the inhibition of apoptosis. Moreover, MLD attenuated CCl4-mediated lipid peroxidation and protein nitrosylation by restoring impaired hepatic nuclear factor erythroid 2-related factor 2 mRNA levels and its dependent antioxidant activities. Furthermore, MLD synergistically decreased mRNA and protein levels of tumor necrosis factor-α, interleukin-1β, and interleukin-6 in the liver. Together, these results suggest that MLD has potential for preventing acute liver injury by inhibiting apoptosis, oxidative stress, and inflammation.

scholarly journals Central nervous system virion detection in acute measles: histopathological, ultrastructural and pathogenetic aspects

1995 ◽  
Vol 37 (2) ◽  
pp. 137-143
Author(s):  
C.L.P. Lancellotti ◽  
C.E.P. Corbett ◽  
M.I.S. Duarte
Keyword(s):  
Electron Microscopy ◽  
Central Nervous System ◽  
Nervous System ◽  
Clinical Diagnosis ◽  
Clinical Manifestations ◽  
Histopathological Changes ◽  
Ultrastructural Studies ◽  
The Central Nervous System ◽  
Neurological Alterations

Histopathological and ultrastructural studies of 23 patients who died with clinical diagnosis of measles were carried out. In 12 cases viral nucleocapsids were searched by electron microscopy and detected in 100% of the cases in the lungs and in 50% of the cases in the central nervous system. They were mostly intranuclear. Histopathological changes associated to neurological alterations and the detection of virion are discussed in relation to acute and delayed clinical manifestations.

scholarly journals A thioacetamide-induced hepatic encephalopathy model in C57BL/6 mice: a behavioral and neurochemical study

2010 ◽  
Vol 68 (4) ◽  
pp. 597-602 ◽  
Author(s):  
Aline Silva de Miranda ◽  
David Henrique Rodrigues ◽  
Luciene Bruno Vieira ◽  
Cristiano Xavier Lima ◽  
Milene Alvarenga Rachid ◽  
...  
Keyword(s):  
Hepatic Encephalopathy ◽  
Liver Damage ◽  
Biochemical Analysis ◽  
Motor Behavior ◽  
Glutamate Release ◽  
Behavioral Symptoms ◽  
Histopathological Analysis ◽  
Suitable Model ◽  
Clinical Disorders ◽  
Release Method

OBJECTIVE: Hepatic encephalopathy (HE) is a neuropsychiatric syndrome resulting from liver failure. In the present study, we aimed to standardize an animal model of HE induced by thioacetamide (TAA) in C57BL/6 mice evaluating behavioral symptoms in association with liver damage and alterations in neurotransmitter release. METHOD: HE was induced by an intraperitoneal single dose of TAA (200 mg/kg, 600 mg/kg or 1,200 mg/kg). Behavioral symptoms were evaluated using the SHIRPA battery. Liver damage was confirmed by histopathological analysis. The glutamate release was measured using fluorimetric assay. RESULTS: The neuropsychiatric state, motor behavior and reflex and sensory functions were significantly altered in the group receiving 600 mg/kg of TAA. Biochemical analysis revealed an increase in the glutamate release in the cerebral cortex of HE mice. CONCLUSION: HE induced by 600mg/kg TAA injection in C57BL/6 mice seems to be a suitable model to investigate the pathogenesis and clinical disorders of HE.

scholarly journals Clomipramine and Benznidazole Act Synergistically and Ameliorate the Outcome of Experimental Chagas Disease

2016 ◽  
Vol 60 (6) ◽  
pp. 3700-3708 ◽  
Author(s):  
Mónica Cristina García ◽  
Nicolás Eric Ponce ◽  
Liliana Maria Sanmarco ◽  
Rubén Hilario Manzo ◽  
Alvaro Federico Jimenez-Kairuz ◽  
...  
Keyword(s):  
Synergistic Effect ◽  
Chagas Disease ◽  
Drug Combination ◽  
Specific Inhibitor ◽  
Chronic Phase ◽  
Control Group ◽  
Histopathological Analysis ◽  
Synergistic Activity ◽  
Content Type

Chagas disease is an important public health problem in Latin America, and its treatment by chemotherapy with benznidazole (BZ) or nifurtimox remains unsatisfactory. In order to design new alternative strategies to improve the current etiological treatments, in the present work, we comprehensively evaluated thein vitroandin vivoanti-Trypanosoma cruzieffects of clomipramine (CMP) (a parasite-trypanothione reductase-specific inhibitor) combined with BZ.In vitrostudies, carried out using a checkerboard technique on trypomastigotes (T. cruzistrain Tulahuen), revealed a combination index (CI) of 0.375, indicative of a synergistic effect of the drug combination. This result was correlated with the data obtained in infected BALB/c mice. We observed that during the acute phase (15 days postinfection [dpi]), BZ at 25 mg/kg of body weight/day alone decreased the levels of parasitemia compared with those of the control group, but when BZ was administered with CMP, the drug combination completely suppressed the parasitemia due to the observed synergistic effect. Furthermore, in the chronic phase (90 dpi), mice treated with both drugs showed less heart damage as assessed by the histopathological analysis, index of myocardial inflammation, and levels of heart injury biochemical markers than mice treated with BZ alone at the reference dose (100 mg/kg/day). Collectively, these data support the notion that CMP combined with low doses of BZ diminishes cardiac damage and inflammation during the chronic phase of cardiomyopathy. The synergistic activity of BZ-CMP clearly suggests a potential drug combination for Chagas disease treatment, which would allow a reduction of the effective dose of BZ and an increase in therapeutic safety.

Management of acute hepatic failure in the critically ill

2016 ◽  
Author(s):  
Deepak Joshi ◽  
Georg Auzinger
Keyword(s):  
Liver Transplantation ◽  
Hepatic Encephalopathy ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Acute Hepatic Failure ◽  
Brain Dysfunction ◽  
Hepatic Necrosis ◽  
Multisystem Disorder ◽  
Grade Iii ◽  
Viable Treatment

Acute liver failure occurs in patients with acute hepatic necrosis resulting in hepatic encephalopathy, jaundice and coagulopathy. Acute liver failure is a multisystem disorder. The management is initially supportive. Intravenous N-acetylcysteine is recommended for all patients. Brain dysfunction is common. Elective intubation is recommended for all patients who develop Grade III hepatic encephalopathy. Liver transplantation is an appropriate and viable treatment for acute liver failure. Early and safe transfer to a transplant centre for transplant assessment is advised.

scholarly journals Synergistic effect of chlorogenic acid and levofloxacin against Klebsiella pneumonia infection in vitro and in vivo

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Shirui Tan ◽  
Jing Gao ◽  
Qingrong Li ◽  
Tieying Guo ◽  
Xiangshu Dong ◽  
...  
Keyword(s):  
Synergistic Effect ◽  
Protein Expression ◽  
Chlorogenic Acid ◽  
Lung Infection ◽  
Klebsiella Pneumonia ◽  
Histopathological Analysis ◽  
Lung Pathology ◽  
Survival Ratio

AbstractThe study aimed to investigate the antibacterial effect and potential mechanisms of chlorogenic acid (CA) in Klebsiella pneumonia (KPN) induced infection in vitro and in vivo. 62 KPN strains were collected from the First People’s Hospital of Yunnan Province. CA and CA combined Levofloxacin (LFX) were detected for KPN biofilm (BF) formation in vitro. The lung infection mice model were established by KPN. The effect of CA (500 mg/kg), LFX (50 mg/kg) and CA combined LFX (250 mg/kg + 25 mg/kg) were evaluated through the survival of mice, the changes of inflammation factors of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β and IL-6 in serum, the histopathological analysis of lung and the protein expression of NLRP3 signaling pathway in vivo. A total of 62 KPNs were isolated and identified, of which 13 (21%) strains were BF positive. 8 (13%) strains were extended spectrum β-lactamase strains (ESBLs), and 20 (32%) strains are ESBLs biofilm positive. In vitro study, CA and LFX showed a synergistic effect on KPN biofilm formation. In vivo mice experiment, CA, especially CA + LFX treated group significantly decreased the serum levels of TNF-α, IL-1β and IL-6, improved the survival ratio and lung pathology changes, and also reduced the protein expression of ASC, caspase 1 p20, IL-1β and phosphor NF-κB p65. CA could effectively alleviate lung infection of KPN infected mice, and the antibacterial effection is strengthened by combined with LFX. The study provide a theroy basis for making rational and scientific antibacterial therapy strategy in clinic.

Caffeic acid abrogates 1,3-dichloro-2-propanol-induced hepatotoxicity by upregulating nuclear erythroid-related factor 2 and downregulating nuclear factor-kappa B

2019 ◽  
Vol 38 (9) ◽  
pp. 1092-1101 ◽  
Author(s):  
TO Ajiboye ◽  
RA Ajala-Lawal ◽  
AB Adeyiga
Keyword(s):  
Caffeic Acid ◽  
Nuclear Factor Kappa B ◽  
Protein Carbonyl ◽  
Related Factor ◽  
Nuclear Factor ◽  
Oxidative Stress Biomarkers ◽  
Acid Pretreatment ◽  
Nuclear Factor Kappa ◽  
Phosphoinositide 3 Kinase ◽  
Factor Α

1,3-dichloro-2-propanol is a food-borne contaminant reported to cause liver injury. In this study, we evaluated the protective influence of caffeic acid on 1,3-dichloro-2-propanol-induced hepatotoxicity in rats. Rats were randomized into five groups (A–E). Rats received distilled water or caffeic acid (10 or 20 mg/kg body weight) for 7 days. In addition, rats were challenged with 1,3-dichloro-2-propanol on day 7. Caffeic acid prevented 1,3-dichloro-2-propanol-mediated alterations in alkaline phosphatase, alanine and aspartate aminotransferases, albumin and total bilirubin in the serum of rats. Furthermore, caffeic acid lowered superoxide ion, hydrogen peroxide and cytochrome P2E1 while increasing the activities of superoxide dismutase, catalase and glutathione S-transferase in the liver of 1,3-dichloro-2-propanol-treated rats. Caffeic acid raised the levels of nuclear erythroid-related factor 2 (Nrf-2), protein kinase A and phosphoinositide 3-kinase. Caffeic acid pretreatment annulled 1,3-dichloro-2-propanol-mediated alterations in the oxidative stress biomarkers; caspase-3, glutathione, malondialdehyde, protein carbonyl and fragmented DNA, in the liver of rats. Contrastingly, caffeic acid lowered 1,3-dichloro-2-propanol-mediated increase in the levels of nuclear factor-kappa B (NF-κB), tumour necrosis factor-α, interleukin-1β (IL-1β) and IL-6. In addition, caffeic acid preserved the morphological features of 1,3-dichloro-2-propanol-treated rats. Results from this study revealed that caffeic acid protects against 1,3-dichloro-2-propanol-induced hepatotoxicity by enhancing the cytoprotective enzymes through Nrf-2 while lowering inflammation through NF-κB.

scholarly journals Effects of administering testosterone undecanoate in rats subjected to physical exercise: effects on the estrous cycle, motor behavior and morphology of the liver and kidney

2010 ◽  
Vol 46 (1) ◽  
pp. 79-89 ◽  
Author(s):  
Moisés Tolentino Bento-Silva ◽  
Maria do Carmo de Carvalho e Martins ◽  
Francisco Leonardo Torres-Leal ◽  
Talvany Luiz Barros ◽  
Ingrid Lara do Nascimento Ferreira de Carvalho ◽  
...  
Keyword(s):  
Estrous Cycle ◽  
Motor Behavior ◽  
Relative Weight ◽  
Hepatic Necrosis ◽  
Study Data ◽  
Vaginal Smear ◽  
Histopathological Analysis ◽  
Testosterone Undecanoate ◽  
Female Wistar Rats ◽  
Liver And Kidney

The aim of the work was evaluate the effects of testosterone undecanoate (TU) treatment combined with moderate physical training on: the estrous cycle, body weight (BW), motor behavior (MB), and the morphohistology of the reproductive system, the liver and kidney in rats. Female Wistar rats (180 g - 250 g) were divided as follows: sedentary + TU (S + TU), trained + TU (T + TU), sedentary + vehicle (S + V), trained + vehicle (T + V). The rats swam 50 min/Day, strapped with a 5% BW load, for 4 weeks. During this training, (BW) was monitored daily as well as the estrous cycle (EC) by vaginal smear. The TU (15 mg/kg s.c) was administered 3 times/week for 4 weeks. At the end of the study, data on MB, BW and morphohistopathological changes in viscera were compiled. The (T + TU) group had on average, a higher (BW) in the fourth week compared to the first week, and (BW) higher than (S + V) and (S + TU) groups. We noted an interruption in the EC and a decrease in weight of ovaries in animals treated with TU. In addition, there was an increase in the relative weight of the heart in groups (T + V) and (T+ TU), and kidneys in group (T + TU). Histopathological analysis showed periportal congestion and isolated foci of hepatic necrosis in rats with TU. Thus, TU combined with training abolished the EC, promoted ovarian atrophy, liver necrosis, cardiac hypertrophy and a decrease in motor activity.

scholarly journals Lactobacillus reuteri DSM 17938 and ATCC PTA 5289 ameliorates chemotherapy-induced oral mucositis

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Nitasha Gupta ◽  
Joao Ferreira ◽  
Catherine Hsu Ling Hong ◽  
Kai Soo Tan
Keyword(s):  
Oxidative Stress ◽  
Oral Mucosa ◽  
Oral Mucositis ◽  
Lactobacillus Reuteri ◽  
Therapeutic Potential ◽  
Histopathological Analysis ◽  
Related Factor ◽  
Intestinal Mucositis ◽  
First Time ◽  
Oral Epithelia

Abstract Oral mucositis (OM) is a common complication of cancer therapy, however OM management remains unsatisfactory. There is a growing interest in the therapeutic potential of probiotics in OM due to positive findings of its use in intestinal mucositis. This study aimed to determine the efficacy and safety of the probiotic combination Lactobacillus reuteri DSM 17938 and ATCC PTA 5289 strains in chemotherapy-induced OM. Mice were divided into 4 groups. PBS/water and PBS/LR groups comprised of mice injected with PBS intraperitoneally (i.p.), and were given water or the mixture of L. reuteri (LR) DSM 17938 and ATCC PTA 5289 in water respectively. The 5-FU/water and 5-FU/LR groups comprised of mice injected with 5-FU i.p., and were given water or L. reuteri DSM 17938 and ATCC PTA 5289 in water respectively. Histopathological analysis revealed that the oral epithelia of the 5-FU/water and 5-FU/LR groups were thinner compared to PBS/water and PBS/LR groups. However, epithelial damage was significantly reduced in the 5-FU/LR compared to 5-FU/water group. Additionally, the 5-FU/LR group showed reduced oxidative stress and inflammation in the oral mucosa. We further showed that L. reuteri reduced oxidative stress through the nuclear factor E2-related factor-2 (Nrf-2) signalling. There was no evidence of translocation of L. reuteri systemically. This study demonstrated for the first time that L. reuteri protected oral mucosa against damage induced by chemotherapy.

Sign in / Sign up

Export Citation Format

Share Document