scholarly journals Comparative efficacy of melatonin in attenuation of endotoxin/LPS induced hepatotoxicity in BALB/c mice

Author(s):  
Ammara Khan ◽  
Ayesha Afzal ◽  
Abdul Rauf ◽  
Akbar Waheed

Background: Sepsis is characterized by overwhelming surge of cytokines and oxidative stress to one of many factors, gram negative bacteria commonly implicated. Despite major expansion and elaboration of sepsis pathophysiology and therapeutic approach; death rate remains very high in septic patients due to multiple organ damage including hepatotoxicity. The present study was aimed to ascertain the adequacy of melatonin (10mg/kg i.p), and its comparability with dexamethasone (3mg/kg i.p), delivered separately and collectively in endotoxin induced hepatotoxicity.Methods: The number of animals in each group was six. Endotoxin/LPS induced hepatotoxicity was reproduced in mice by giving LPS of serotype E. coli intraperitoneally. Preventive role was questioned by giving the experimental agent half an hour prior to LPS injection whereas therapeutic potential of the experimental agent was searched out via post LPS delivering. The extent of liver damage was adjudged via serum alanine aminotransferases (ALT) and aspartate aminotransferase (AST) estimation along with histopathological examination of liver tissue.Results: Melatonin was prosperous in aversion (Group 3) and curation (Group 4) of LPS invoked hepatotoxicity as evident by lessening of augmented ALT (≤0.01) and AST (≤0.01) along with restoration of pathological changes on liver sections (p≤0.05). Dexamethasone given before (Group5) and after LPS (Group 6) significantly (p≤0.05) attenuated LPS generated liver injury. Combination therapy with dexamethasone in conjunction with melatonin (Group 7) after LPS administration tapered LPS evoked hepatic dysfunction statistically considerably, however the result was comparable to single agent therapy.Conclusions: Melatonin set up promising results in endotoxin induced hepatotoxicity and can be used therapeutic adjuncts to conventional treatment strategies in sepsis induced liver failure. Combination therapies however generated no synergistic results.

Author(s):  
Ammara Khan ◽  
Ayesha Afzal ◽  
Hammad A. Butt ◽  
Akbar Waheed

Background: Even though with immense improvement and extensive understanding of pathophysiology of sepsis induced organ failure and affected population, it continues to put hundreds of people worldwide to eternal sleep due to lack of targeted therapy. Newer treatment modalities is the dire need of time. The present study was aimed to ascertain the adequacy of phosphodiesterases inhibitor - pentoxifylline (75mg/kg i.p) in endotoxin/LPS induced hepatotoxicity in BALB/c mice.Methods: The number of animals in each group was six. Endotoxin/lipopolysaccharides induced hepatotoxicity was reproduced in mice by giving lipopolysaccharide of serotype E. coli intraperitoneally. To ascertain the Preventive role, pentoxifylline was administered forehand LPS injection whereas therapeutic potential adjuged via post LPS delivering. The extent of liver damage was evaluated through serum alanine aminotransferases (ALT) and aspartate aminotransferase (AST) estimation along with histopathological examination of liver tissue.Results: Results set forth that serum ALT, AST levels and histological alteration abated considerably (p ≤0.05) both in animals subjected to pentoxifylline pre and post-treatment.Conclusions: Pentoxifylline set up promising results in endotoxin induced hepatotoxicity and can be used therapeutic adjuncts to conventional treatment strategies in sepsis induced liver failure.


2020 ◽  
Vol 25 (1) ◽  
pp. 1
Author(s):  
Riyam Ameen Salih1 ◽  
Abdul–Karim Salim Mahood2 ◽  
Samira Abdul- Hussain Abdulla3 ◽  
, Mohammed Abdullah Ajeel4

Drugs induced nephrotoxicity now considered as an essential reason for kidney failure. Aminoglycoside anti-infection agents, for example, gentamicin, which causes ototoxicity and nephrtotoxicity as a side effect , this research is centered around the utilization of natural materials as an antioxidants against the lethal oxidative activity that applied on the kidney cells ,the most imperative one of these materials is the honey. This work aimed to assess the defensive impact of citrus honey against the histopathological and biochemical harms of gentamicin induced nephrotoxicity .24 locally breed rabbits (Oryctolagus cuniculus) were used and divided into 4 study groups (6 rabbits per each group), group 1 received I.P daily dose of normal saline (control), group 2 received (80 mg/kg/day) I.P dose of gentamicin, group 3 received (80mg/kg/day) of gentamicin I.P dose in combination with oral dose of Citrus Honey625 mg/kg/day for 14 days and group 4 received (80mg/kg/day) of gentamicin I.P dose in combination with extra dose of Citrus Honey orally for 14 days. All animals (at 15th day) were anesthetized by ether and sacrificed; blood samples were gathered for the subsequent measurement of the serum creatinine, urea and albumin  while an isolated kidney was kept in 10 % of formaldehyde for the histopathological examination. The results demonstrated that gentamicin causes nephrotoxicity showen by elevation of serum level of creatinine, urea and  a decrease in the serum albumin. While the administration of honey in combination with gentamicin reduced the nephro-toxic effect of gentamicin that represented by a reduction of the serum creatinine and urea with improvement of the kidney histological findings.This study concluded that, honey decreased nephrotoxic effect of  gentamicin   http://dx.doi.org/10.25130/tjps.25.2020.001  


2021 ◽  
Vol 23 (Supplement_1) ◽  
pp. i12-i12
Author(s):  
Sydney Peck ◽  
Emily Owens ◽  
Amy Smith

Abstract Medulloblastoma (MB) is the most common malignant central nervous system (CNS) cancer diagnosed in childhood and is divided into four subtypes: WNT-activated, SHH-activated, Group 3 (Non-WNT, Non-SHH), and Group 4 (Non-WNT, Non-SHH). Non-WNT/Non-SHH make up roughly two-thirds of MB and have the least understood pathogenesis with substantial intratumoral heterogeneity. Therapeutic targets and treatment strategies for Group 3 and 4 patients therefore remain unclear. In this report we present a 16-year-old patient with standard risk Group 4 medulloblastoma and multiple midline defects. The patient’s medical history was remarkable for a cleft lip (which healed in utero), a notable heart murmur, an inguinal hernia repair at 3 months of age, and significant pectus excavatum. This patient was diagnosed at age 12 with a MB. Tumor cells were negative for GAB-1, p53 stain was positive for approximately 1–2% of tumor cells, no evidence on monosomy 6, MYC or MYCN amplification. The family history is significant for paternal biliary cancer. The patient was treated as per ACNS0331 and is approximately 36 months off-therapy. This case presents an interesting instance of a CNS tumor arising within the microenvironment of wide-spread dysregulated development. Single cases do not provide any substantiative evidence. However, they do give insight on factors which may drive oncogenesis and may provide an indication as to whether we should continue to pursue targeted therapy for Group 3/4 uniformly or move towards personalized therapy strategies in this group patients.


Author(s):  
Shaik Amjad ◽  

investigate the therapeutic potential of CA against chronic Aluminium Chloride (AlCl3) exposure induced rats. Wistar albino rats were segregated into four groups: group 1-control rats, group 2-rats received AlCl3 (300 mg/kg body weight, every day orally) for 60 days, rats in group 3-received CA (500 mg/kg body weight, orally) and group 4 rats were initiated with both AlCl3 and CA treatment.


2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Osman Tiryakioglu ◽  
Kamuran Erkoc ◽  
Bulent Tunerir ◽  
Onur Uysal ◽  
H. Firat Altin ◽  
...  

Objective. The objective of this study was to examine the effects of iloprost and N-acetylcysteine (NAC) on ischemia-reperfusion (IR) injuries to the gastrocnemius muscle, following the occlusion-reperfusion period in the abdominal aorta of rats.Materials and Methods. Forty male Sprague-Dawley rats were randomly divided into four equal groups.Group 1: control group. Group 2 (IR): aorta was occluded. The clamp was removed after 1 hour of ischemia. Blood samples and muscle tissue specimens were collected following a 2-hour reperfusion period.Group 3 (IR + iloprost): during a 1-hour ischemia period, iloprost infusion was initiated from the jugular catheter. During a 2-hour reperfusion period, the iloprost infusion continued.Group 4 (IR + NAC): similar to the iloprost group.Findings. The mean total oxidant status, CK, and LDH levels were highest in Group 2 and lowest in Group 1. The levels of these parameters in Group 3 and Group 4 were lower compared to Group 2 and higher compared to Group 1 (P<0.05). The histopathological examination showed that Group 3 and Group 4, compared to Group 2, had preserved appearance with respect to hemorrhage, necrosis, loss of nuclei, infiltration, and similar parameters.Conclusion. Iloprost and NAC are effective against ischemia-reperfusion injury and decrease ischemia-related tissue injury.


2017 ◽  
Vol 89 (2) ◽  
pp. 134
Author(s):  
Murat Tuken ◽  
Mustafa Zafer Temiz ◽  
Emrah Yuruk ◽  
Asuman Orcun Kaptanagasi ◽  
Kayhan Basak ◽  
...  

Objectives: The aim of this study is to evaluate the effects of the herbal agent in the prevention and treatment of bacterial cystitis in a rat model. Material and Methods: A total of twenty-eight male Sprague- Dawley rats were divided into four groups. Group-1 constituted the control group (operated and normal saline injected into the bladder, received only drinking water for 7 days); Group-2 constituted the no-treatment group (operated, E.coli J96 strain injected into the bladder, received only drinking water for 7 days); Group-3 constituted the short-term treatment (operated, E.coli J96 strain injected into the bladder, received the herbal agent added into drinking water for 7 days) and Group-4 constituted the long-term treatment (operated, E. coli J96 strain injected into the bladder, received herbal agent added into drinking water for 14 days). At the end of the pre-defined treatment periods of duration, the rats were sacrificed, urine samples collected from the bladder for culture and bladders were harvested for histopathological evaluation. Urine culture results and histopathological findings were comparatively evaluated between the groups. Results: Urine cultures were positive for implanted E. coli strains in 0%, 85.7%, 42.8% and 0% of rats in Group 1, Group 2, Group 3 and Group 4, respectively (p = 0.001). Although histopathological evaluation revealed increased vascular dilation in the bladder specimens obtained from Group 2 and Group 3 (p = 0.028) no significant difference was noticed in level of inflammation (p = 0.610), edema (p = 0.754) and thickness of uroepithelium (p = 0.138). Conclusion: While long term (14 days) treatment with an herbal agent added into the drinking water resulted in complete clearance of urine from E. coli; shorter application of the agent revealed partial clearance. Further clinical studies are needed to support our results.


2006 ◽  
Vol 88 (2) ◽  
pp. 176-180 ◽  
Author(s):  
Mehmet Faruk Geyik ◽  
Mustafa Aldemir ◽  
Salih Hosoglu ◽  
Celal Ayaz ◽  
Selda Satilmis ◽  
...  

INTRODUCTION The aim of this study was to investigate the effect of Saccharomyces boulardii treatment on preventing bacterial translocation in an obstructive jaundice animal model. MATERIALS AND METHODS Sixty adult rats were divided into five groups: group 1 – the sham-operated group; group 2 – the common bile duct ligation group; group 3 – the S. boulardii group; group 4 – the ampicillin-sulbaktam group; and group 5 – the S. boulardii plus ampicillin-sulbaktam group. The saline, antibiotics and S. boulardii were given, respectively, for a 7-day period as a single dose per day via temporary orogastric intubation. Seven days following the obstructive jaundice, the animal had laparatomy under sterile conditions. Segments of ileum were removed for histopathological examination. Blood, liver, spleen and mesenteric lymph nodes were taken for microbiological culture. RESULTS Bacterial translocation rates were 0% in the sham-operated group, 83% in group 2, 42% in group 3, 42% in group 4 and 33% in group 5. Bacterial translocation significantly increased in group 2 compared to groups 3, 4 and 5 (P = 0.001). The bacterial counts (CFU/g) of group 2 were significantly higher than those of groups 3, 4 and 5 (P = 0.001). Histopathological examination of ileum specimens revealed a significant decrease in the heights of villi in groups 2–5 compared to the sham-operated group (P = 0.001). The mean villus height in groups 3 and 5 was significantly higher than that of group 4 (P = 0.001). CONCLUSIONS S. boulardii was found to be effective in the successful control of translocation and improvement of intestinal barrier function.


2005 ◽  
Vol 53 (3) ◽  
pp. 325-335 ◽  
Author(s):  
R. Cöl ◽  
E. Keskin ◽  
B. Atalay

Pentoxifylline (PTX, a methylxanthine derivative) has been found to interrupt early gene activation for tumour necrosis factor, interleukin-1, interleukin-6 and tissue factor production and to improve survival from experimental sepsis. During endotoxaemia, lipopolysaccharide (LPS, endotoxin) and proinflammatory cytokines trigger the development of disseminated intravascular coagulation (DIC) via the tissue factor-dependent pathway of coagulation. The present study was undertaken to determine whether pentoxifylline could prevent coagulation disturbances in LPS-treated rabbits. Endotoxaemia was induced with E. coli lipopolysaccharide in New Zealand White rabbits. Forty rabbits were used and divided into four equal groups. Group 1 served as a control group; Group 2: lipopolysaccharide was injected intravenously, Group 3: pentoxifylline was injected intraperitoneally, Group 4: lipopolysaccharide and pentoxifylline were injected simultaneously. Blood samples were collected 6 h after the treatments. In rabbits with endotoxin-induced DIC, platelet count, leukocyte count, percentage of differential leukocyte values, fibrinogen level, antithrombin III (AT-III) and protein C (PC) activity were decreased. Moreover, activated partial thromboplastin time (APTT) and prothrombin time (PT) were prolonged when compared to the control group. In conclusion, haemostatic disturbances associated with endotoxin-induced DIC were moderately suppressed by the administration of PTX.


2014 ◽  
Vol 5 (3) ◽  
pp. 22-29
Author(s):  
Yuliya Lazarevna Naboka ◽  
Aleksandr Nikolayevich Rymashevskiy ◽  
Eteri Goneriyevna Svirava ◽  
Larisa Ivanovna Vasilyeva ◽  
Lidiya Yeliseyevna Bragina ◽  
...  

We have examined 96 conditionally healthy primigravidae and 96 newborns. Group 1 (n = 51): gravidae with normal course of preg-nancy and delivery, group 2 (n = 45): gravidae with normal course of pregnancy and deliveries by caesarian section (indications for the operation - severe myopia), group 3 (n = 51): newborns from gravidae of group 1, group 4 (n = 45): newborns from gravidae of group 2. Purpose: study of the development of microbiota in the large intestine of newborns depending on various delivery methods. Enterococcus sp. (58,2 %), S. epidermidis (55,7 %), Corynebacterium sp. (53,1 %), E. coli (41,7 %) dominated in meconium microbiota. By the day 5 in group 3 we registered more frequently (p < 0,05) Bifidobacterium sp., Corynebacterium sp., E. coli, in group 4 - Klebsiella sp. Independently from the delivery method, by day 5 we observed in the feces of newborns increased (р < 0,5) content of Bifidobacterium sp., Lactobacillus sp., E. coli, Enterococcus sp., and S. aureus.


2014 ◽  
Vol 81 (5) ◽  
pp. 1782-1787 ◽  
Author(s):  
Karla Cameron-Veas ◽  
Marc Solà-Ginés ◽  
Miguel A. Moreno ◽  
Lorenzo Fraile ◽  
Lourdes Migura-Garcia

ABSTRACTThe aim of this study was to evaluate if the treatments with ceftiofur and amoxicillin are risk factors for the emergence of cephalosporin resistant (CR)E. coliin a pig farm during the rearing period. One hundred 7-day-old piglets were divided into two groups, a control (n= 50) group and a group parenterally treated with ceftiofur (n= 50). During the fattening period, both groups were subdivided in two. A second treatment with amoxicillin was administered in feed to two of the four groups, as follows: group 1 (untreated,n= 20), group 2 (treated with amoxicillin,n= 26), group 3 (treated with ceftiofur,n= 20), and group 4 (treated with ceftiofur and amoxicillin,n= 26). During treatment with ceftiofur, fecal samples were collected before treatment (day 0) and at days 2, 7, 14, 21, and 42 posttreatment, whereas with amoxicillin, the sampling was extended 73 days posttreatment. CRE. colibacteria were selected on MacConkey agar with ceftriaxone (1 mg/liter). Pulsed-field gel electrophoresis (PFGE), MICs of 14 antimicrobials, the presence of cephalosporin resistance genes, and replicon typing of plasmids were analyzed. Both treatments generated an increase in the prevalence of CRE. coli, which was statistically significant in the treated groups. Resistance diminished after treatment. A total of 47 CRE. coliisolates were recovered during the study period; of these, 15 containedblaCTX-M-1, 10 containedblaCTX-M-14, 4 containedblaCTX-M-9, 2 containedblaCTX-M-15, and 5 containedblaSHV-12. The treatment with ceftiofur and amoxicillin was associated with the emergence of CRE. coliduring the course of the treatment. However, by the time of finishing, CRE. colibacteria were not recovered from the animals.


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