Sinusoidal Congestion Research Articles

Effects of silibinin on hepatic warm ischemia-reperfusion injury in the rat model.

Objective(s):Liver ischemia-reperfusion injuries (I/RI) are typically the main causes of liver dysfunction after various types of liver surgery especially liver transplantation. Radical components are the major causes of such direct injuries. We aimed to determine the beneficial effects of silibinin, a potent radical scavenger on liver I/RI.Materials and Methods:Thirty-two rats were divided into 4 groups. Group I: VEHICLE, the rats underwent laparotomy and received DMSO, group II: SILI, laparotomy was done and silibinin was administered. Group III: I/R, the rats received DMSO and were subjected to a liver I/R procedure and group IV: I/R+SILI, the animals underwent the I/R procedure and received silibinin. After 1 hr of ischemia followed by 3 hr reperfusion, blood was collected to evaluate the serum marker of liver injuries. Hepatic tissue was harvested to investigate glycogen content, histological changes, and vasoregulatory gene expression.Results:Results showed that serum AST, ALT, LDH, GGT, ALP, and hyaluronic acid (HA) increased significantly in I/R group compared with the VEHICLE group. Silibinin reduced this elevation except for GGT. Silibinin inhibited hepatocyte vacuolization and degeneration, endothelium damages, sinusoidal congestion and inflammation, and glycogen depletion during I/R. ET-1 mRNA was overproduced in the I/R group compared with the VEHICLE group which was decreased by silibinin. KLF2 and eNOS expression was reduced during I/R compared with the VEHICLE group. Silibinin elevated KLF2 expression but had no meaningful effect on eNOS expression.Conclusion:Silibinin protected the liver from I/RI. Silibinin could improve liver circulation by preventing sinusoidal congestion, inflammation, and perhaps modification of the vasoregulatory gene expression.

Studi Toksisitas Organofosfat (Diazinon) Terhadap Gambaran Histopatologi Hepar dan Kadar Malondialdehyde (MDA) dalam Serum Tikus (Rattus norvegicus)

Diazinon is an insecticide that has a higher toxicity than other insecticides. Normally, insecticides are detoxified by liver, but this process produced free radicals which causes cell damage. Free radicals also increase lipid peroxidation which directly increase malondialdehyde levels. This research was aimed to determine the influence of diazinon toxicity to the liver histopathology and levels of malondialdehyde (MDA) in the serum of rats (Rattus norvegicus). The rats were divided into 4 groups which consist of negative control group and three experimental groups which were given diazinon 20 mg/kgBW (P1), 40 mg/ kgBW (P2), and 60 mg/ kgBW (P3). The rats were given diazinon for 8 weeks orally. The parameters used in this research was liver histopathology with hematoxilin eosin stain and Malondialdehyde levels with Thiobarbituric test. Liver histopathology was analyzed in descriptive qualitative and the level of MDA was analyzed quantitatively using ANOVA and Tukey's exact test with α = 0.05. The result of this research showed the influence of organophosphate (diazinon) on liver histolopathology was shown by inflammatory cells infiltration in hepatic parenchyma, sinusoidal congestion, and cytoplasmic vacuolation of the hepatocytes. Statistical analysis proved that the diazinon was able to increase the level of MDA serum significantly (p<0,05) up to 71% in experimental group P1 (dose 20 mg/kgBW), which the increase level of MDA serum depend on dose of diazinon. This research concluded that diazinon is one of the organophosphate pesticide that toxic based on liver histopathology and MDA serum levels.

Pollution induced change of liver of Oreochromis niloticus: metals accumulation and histopathological response

The present study, pointed to assess heavy metal accumulation like Aluminum (Al), Cadmium (Cd), Chrome (Cr), Cobalt(Co), Copper(Cu), Iron(Fe), Lead (Pb), Manganese(Mn), Nickel(Ni), Selenium(Se) and Zinc(Zn) in water, sediments and liver of Oreochromis niloticus, which collected from sewage water in El-kharja, New Valley, Egypt using inductively coupled plasma mass spectrometry (ICP-MS). Also, the histopathological changes of liver of Oreochromis niloticus were reported. These histopathological changes were detected using different staining types as a pollution biomarker. Iron showed the highest accumulation level in water (9.06±0.86 ppm), sediments (175.1±20.8 ppm) and liver (158.17±38.59 ppm), followed by Al> Mn> Ni> Zn> Pb> Cr> Se> Cu> Co> Cd. However, these elements showed Fe> Al> Ni> Mn> Cr> Cu> Zn> Pb> Cd> Se> Co accumulation trend in sediments. In liver these metals showed Fe> Se>Al> Zn>Mn> Cu>Ni> Cr> Pb> Co> Cd trend. Histopathological examination of fish liver showed signs of progressive alterations such as disorganization of architecture of liver cells, hydropic degeneration and vacuolation of hepatocytes. Also, dilation and congestion in blood sinusoids, hypertrophic and increase in number of küpffer cells were chronicled. Sever deposition of hemosiderin pigments were reported while necrosis with pyknotic nucleus and focal histopathological characters were observed side by side with normal cell. Our results concluded that water, sediment and liver accumulation toxicity tests and histopathological changes of liver may be associated, and these approaches may be used together to describe the environmental state and water quality assessment.

Differential Expression of CD3, TNF-α, and VEGF Induced by Olanzapine on the Spleen of Adult Male Albino Rats and the Possible Protective Role of Vitamin C.

Olanzapine is an antipsychotic drug effective in the treatment of stress-associated psychiatric illnesses, but its effect on the spleen remains unclear. Vitamin C is essential for the optimum function of the immune system. We aim to investigate the effect of Olanzapine on spleen structures and to assess the protective effect of vitamin C. Forty adult male albino rats were divided into four groups: group (I), a control; group (II), rats were given vitamin C at 40 mg/kg body weight; group (III), rats were given Olanzapine at 2 mg/kg body weight; and group (IV), rats were given vitamin C and Olanzapine at the same dose of group (II) and group (III) for one month. The hematoxylin and eosin (H&E) of the olanzapine treated group showed focal areas of cellular depletion and a decrease in the size of the white pulp. The red pulp was expanded and showed marked congestion and dilatation of blood sinusoids. Cluster of differentiation 3 (CD3) was significantly reduced, however both tumor necrosis factor alpha (TNF-α), and vascular endothelial growth factor (VEGF) were significantly higher. The administration of vitamin C repaired structural and immunohistochemical changes via increased CD3 and decreased TNF-α and VEGF. Therefore, the oxidative and the inflammatory pathways may be the possible mechanisms underlying olanzapine immunotoxicity. Vitamin C exerted immune modulator and antioxidant effects against olanzapine.

Influence of ferulic acid consumption in ameliorating the cadmium-induced liver and renal oxidative damage in rats.

The aim of this study relates to the modulatory role of ferulic acid (FA) against cadmium (Cd)-induced oxidative stress in the liver and kidney of male Wistar albino rats. Cd is an extremely toxic industrial and environmental pollutant and is well known for its varied toxic clinical manifestations. FA is a derivative of curcumin and a ubiquitous phenolic compound having a wide range of therapeutic activities. In the current study, Cd (10mg/kg) was administered subcutaneously for 15 and 30days to induce hepato-renal toxicity. Cd concentration was found to be significantly high in Cd-intoxicated rats (liver > kidney) while the supplementation of FA (50mg/kg) significantly reduces the Cd concentration in liver and kidney tissues. Reduced body and organ weights and food and water consumption and increased rectal temperature were noticed in Cd-treated rats while these parameters were significantly ameliorated in FA-supplemented rats. Liver and kidney damage induced by Cd was significantly revealed by the reduction in serum total protein contents (TPC) and increased activities of serum nitric oxide (NO) levels and hepato-nephrotoxicity marker enzymes, namely aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), lactic dehydrogenase (LDH), AST:ALT ratio, uric acid, urea, urea nitrogen, and creatinine, along with the increased levels of hepatic and renal oxidative stress markers, namely lipid peroxidation (MDA levels), lipid hydroperoxides (LOOH), protein carbonyl content (PCC), total oxidant status (TOS), and oxidative stress index (OSI) in liver and kidney tissues. In addition, the toxicity of Cd was also evidenced by a significant decrease in the levels of total thiols (TTH), total antioxidant concentration (TAC), enzymatic antioxidants (superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx)), and non-enzymatic antioxidants (reduced glutathione (GSH) and total free sulfhydryl groups (TSH)). Administration of FA significantly restored the serum total protein levels and activities of serum NO levels and hepatic and renal marker enzymes to normal levels in comparison with Cd-intoxicated rats. Furthermore, FA significantly reduced the oxidative stress markers and recuperated the levels of antioxidant defense in the liver and kidney as evidenced by native PAGE and spectrophotometric assays, correlation and regression analysis and multivariate analysis of variance (MANOVA), and inferring the antioxidant role of FA. Histopathological damage due to Cd intoxication in the liver and kidney is demonstrated as vasodilatation and congestion in central veins and sinusoids as well as around the glomerulus, infiltration of mixed inflammatory cells and peripheral hemorrhage, hemorrhagic and enlarged sinusoids, disorganization of the hepatic parenchyma, focal necrosis, swelling of hepatocytes, calcified tissue inside blood vessels, hepatocyte degeneration and vacuolization of liver cells, hyaline casts, degenerated glomerulus with wide space and detached basement membrane, distal tubule with wide lumen, deformed proximal tubules with detached brush border, and degeneration and hyalinization of glomerular tuft. But, FA significantly reduced the toxicity of Cd and protected the normal histological architecture of the liver and kidney tissues. Cd-intoxicated rats were associated with a significant upregulation of TNF-α, COX-2, and HSP70 proteins, whereas treatment with FA caused downregulation of the above inflammatory markers indicating the anti-inflammatory role of FA. Principal component analysis (PCA) and Euclidean similarity measure studies clearly indicate that the liver is more prone to Cd toxicity than the kidney and FA supplementation significantly prevents oxidative stress, augmenting antioxidative status, and regaining histological parameters of the liver and kidney to normal, indicating hepato-nephroprotective, antiradical, antioxidant, and anti-inflammatory effects of this phenolic compound.

The positive effect of metformin and metronidazole on the diabetic rats experimentally

Diabetes mellitus is considering most serious disease of endocrine, it affecting large number of people in worldwide. This study was performed to insured the effect of combination of metformin and metronidazole on disorder in metabolic that concomitant with injection of alloxan IP induced diabetes in rats. In this study forty male rats: divided into four groups including control group G1, alloxn group (150 mg/kg single dose) G2, alloxn group orally treated with metformin (150mg/kg/BW) G3, and alloxn group orally treated with metformin (150mg/kg/BW) and metronidazole (500mg/kg/BW) G4. The experiment last for 14 days. The result shows marked increase in MDA, glucose and also in liver enzymes, lipid profiles and even observed disorder in kidney function test by increased in the creatinine, urea, and uric acid levels. In addition to study the histological changes in diabetic liver of rats characterized by kupffer cells activation, dilation and congestion of central vein and hepatic sinusoids. Administration of metformin and combination of metformin and metronidazole, result in significant reduction return abnormal parameters to the normal values. Also correct the abnormal histological changes of liver.

Transient Inhibition of mTORC1 Signaling Ameliorates Irradiation-Induced Liver Damage.

Recurrent liver cancer after surgery is often treated with radiotherapy, which induces liver damage. It has been documented that activation of the TGF-β and NF-κB signaling pathways plays important roles in irradiation-induced liver pathologies. However, the significance of mTOR signaling remains undefined after irradiation exposure. In the present study, we investigated the effects of inhibiting mTORC1 signaling on irradiated livers. Male C57BL/6J mice were acutely exposed to 8.0 Gy of X-ray total body irradiation and subsequently treated with rapamycin. The effects of rapamycin treatment on irradiated livers were examined at days 1, 3, and 7 after exposure. The results showed that 8.0 Gy of irradiation resulted in hepatocyte edema, hemorrhage, and sinusoidal congestion along with a decrease of ALB expression. Exposure of mice to irradiation significantly activated the mTORC1 signaling pathway determined by pS6 and p-mTOR expression via western blot and immunostaining. Transient inhibition of mTORC1 signaling by rapamycin treatment consistently accelerated liver recovery from irradiation, which was evidenced by decreasing sinusoidal congestion and increasing ALB expression after irradiation. The protective role of rapamycin on irradiated livers might be mediated by decreasing cellular apoptosis and increasing autophagy. These data suggest that transient inhibition of mTORC1 signaling by rapamycin protects livers against irradiation-induced damage.

THE ROLE OF THYMOQUINONE IN AMELIORATING THE HEPATOXIC EFFECT OF DIAZINON IN MALE RATS

Diazinon (DZN) is one of most dangerous hepatotoxic organophosphorous insecticides used in veterinary practices which induces oxidative stress. The present study aimed to evaluate the ameliorative role of thymoquinone (TQ) in diazinon toxicity. Forty nine male albino rats and were divided into seven groups (n =7 for each). The first group (c-ve group) orally received saline daily all over the experiment (8 weeks). The second group (c+ve1) orally received DZN (15 mg/kg body weight, b-w) for the first four weeks and saline for the next four weeks. The third group (c+ve2) orally received saline for the first four weeks and DZN (15 mg /kg b-w) for the following four weeks. The fourth group (DZN-TQ 10 mg group) received DZN (15 mg/kg b-w) daily for the first four weeks then TQ (10 mg/kg b-w) for the next four weeks. The fifth group (TQ 10 mg-DZN) orally treated with TQ (10 mg/kg b-w) and DZN (15 mg/kg b-w) for the next for weeks. The sixth group (DZN-TQ 5 mg group) received DZN (15 mg/kg b-w) for first four weeks and TQ (5 mg/kg b-w) for the following four weeks 5 mg. The seventh group treated by TQ (5 mg/kg b-w) daily for the first four weeks and DZN (15 mg/kg b-w) for the following four weeks (TQ 5 mg-DZN group). DZN intoxicated groups showed macrocytic hypochromic anemia and serum biochemical alteration related to liver injury, including elevation of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and a significant decrease in total protein and albumin. Furthermore, these groups also exhibited a significant increase in liver tissue malondialdehyde (MDA), significant decrease in total antioxidant capacity (TAC) and catalase (CAT) activities and over-expression of the two apoptotic hepatic genes Bax and caspase 3. Administration of DZN also resulted in hepatic vacuolation, necrosis and congestion of hepatic sinusoids. Thymoquinone ameliorated the most deleterious effect of diazinon on hematological, biochemical, antioxidant, molecular and histopathological parameters in a dose dependent manner and a prophylactic strategy is better than therapeutic one.Key words: diazinon; thymoquinone; oxidative stress; hepatotoxicity

Prophylactic Effects of Some Nigerian Higher Fungi on Malaria Parasite, Plasmodium berghei berghei in BALB/c Strain Albino Mice

The preventive abilities of some Nigerian higher fungi; Pleurotus pulmonarius, Fomes lignosus, Lentinus subnudus, Termitomyces robustus, Pleurotus tuber-regium collected from wood substrates, and the combined extracts (40 mg/mL) were studied against malaria parasite, Plasmodium berghei berghei to exploit them as medicinal agents. The fruit bodies were extracted with ethanol using soxhlet apparatus. Six hundred and twelve 4- 5 weeks old BALB/c mice (average weight 21 g) were assigned into 30 groups of twelve mice each. They were orally treated with 0.1 mL extracts of 4, 0.4, 0.04, 0.004, 0.0004 mg/mL before infecting with 0.2 mL of 5x106 parasitized erythrocytes. Chloroquine,CQ (20 mg/kg) served as controls. Liver and kidney were examined for histological changes. Parasitemic level, packed cell volume (PCV) and weights of animals were checked using standard methods. Descriptive statistics and ANOVA (at p= 0.05) were used for data analysis. Lentinus subnudus produced the highest decrease of parasitemia (30%), and recorded the least loss of PCV (27%), while Pleurotus tuber-regium produced the least weight loss of 26.5%. All the mushroom extracts produced same effect as CQ at concentrations 0.4 and 0.04 mg/mL. The tissues of infected animals without extracts had abnormalities. There were no histological damage in tissues of uninfected animals. Pre-infection treatment produced mild abnormal conditions from severe periportal infiltration and marked sinusoidal congestion. The extracts could be formulated into drugs against malaria however, appropriate dosage must be known.

Toxicological evaluation of Picralima nitida in rodents

Picralima nitida (Stapf) T. Durand and H. Durand (Apocynaceae), over the years has shown wide range of usage in African folk medicine and its safety profile in instances of prolonged use and pregnancy are major concerns. The study aimed to extensively investigate the toxicological effects of Picralima nitida in albino rodents and make appropriate extrapolations to humans.In the first phase of the experiment which evaluated the genotoxicity and subchronic toxicity of P. nitida, a total of 40 albino rats (male and female) were randomized into 4 groups of 10 animals per group. Group 1 (control group) was orally administered with 10 ml/kg of distilled water. Animals in Groups 2 to 4 were administered with aqueous seed extract of the plant at 100, 200, 400 mg/kg body weight/day, respectively. Oral administration at the designated doses was continued for 90 days after which they were sacrificed by cervical dislocation for subchronic toxicological assessment. In the genotoxicity phase, 30 female mice were randomized into 5 groups, the control group was treated with 10 ml/kg of distilled water, groups 2 to 4, treated with 100 mg/kg, 200 mg/kg and 400 mg/kg doses of extract, and the 5th group had cyclophosphamide (0.1 mg/kg). The mice were sacrificed on the 28th day for bone marrow sampling for genotoxicity testing.In the second phase of the experiment which evaluated the teratogenicity of P. nitida, graded doses of the extract were administered to pregnant rats from day 1–19. Three groups of 6 female rats per group were administered 75, 150 and 300 mg/kg aqueous extract of P. nitida and a fourth group of 6 rats used as control was administered distilled water at 10 ml/kg. On day 20, 3 dams from each group were sacrificed and the foetuses were harvested through abdominal incision for physical examination. The 3 remaining dams were allowed to litter. The litters were sacrificed at 6 weeks for biochemical, haematological and histological analyses.The LD50 determined was 707.107 mg/kg. The aqueous seed extract of P. nitida was found to be genotoxic at all the test doses. There were no significant alterations in haematologic and renal parameters following subchronic administration. Notable dynamics were observed in hormonal characteristics: there was a significant dose-dependent reduction in FSH while oestradiol and progesterone showed dose-dependent increase. Furthermore, P. nitida may cause hepatopathy as shown by hepatic venous and sinusoidal congestion on hepatic histology. Also, there is non-significant reduction in total cholesterol and LDL. No significant alteration in glucose level.Furthermore, the extract produced a statistically significant decrease in birth weight (p < 0.0001). The extract induced a significant (p < 0.05) increase in creatinine and transaminase levels in the first filial of group 150 mg/kg. The platelet count was increased in all treated group (p < 0.005). All the histology of kidney in 150 mg/kg group showed vascular congestion.In conclusion, the aqueous seed extract of P. nitida has teratogenic effects and should not be used in pregnant women. Also, P. nitida is highly genotoxic and may cause hepatic damage and depletion of glutathione pool on chronic use, thereby causing oxidative stress and its potential sequelae.

Toxicity of Water Soluble Fractions of Petroleum Crude Oil and its Histopathological Alterations Effects on Red Tilapia Fish

Five treatments including control and four concentrations of water soluble fraction (WSFs) crude oil (5 ppm, 6 ppm, 8 ppm and 10 ppm) were made. Triplicate and ten fish of red tilapiawith an average weight of 8g ± 1.5 were incubated for 96 hours. The 96 hours LC50 was determined (5.25ppm). Histopathological examination of the fish was made for liver, gills, kidney, male gonad and female gonad. Liver showed congestion of blood vessels and hepatic sinusoids with focal necrotic changes of hepatocytes. Gills showed congestion of blood vessels, hyperplasia and adhesion of secondary gill lamellae. Kidney showed congestion of blood vessels and degeneration of renal tubules. Male gonad showed degeneration and necrosis of some seminiferous tubules, edema and severe reduction in all spermatogenic stages and degeneration and Female gonad showed severe necrosis of developmental stages of oocytes along with degenerated mature ripped oocytes in WSFs treated fish compared to control group.

Histopathology of Hepatic Sinusoidal Obstruction Syndrome After Neoadjuvant Oxaliplatin-Based Chemotherapy

Abstract Sinusoidal obstruction syndrome („blue liver syndrome“) has been frequently associated with oxaliplatin-based neoadjuvant chemotherapy in patients with colorectal liver metastasis. Hepatotoxic vascular lesions in the nontumourous liver parenchyma result in hypoperfusion and tissue hypoxia leading to lower tumour response to oncologic treatment and to increase the risk of liver metastasectomies. Furthermore, hepatic parenchyma injuries could be aggravated by hepatic resection itself. Contrary to standard surgical techniques, radiofrequency assisted liver resection significantly reduce harmful intraoperative blood loss and perfusion-reperfusion effects. We compared histological alterations in 59 specimens of bloodless radiofrequency-assisted liver recetions made for colorectal metastases to those in 38 specimens of standard liver resections. In general, the main histologic alterations in both examined groups related to oxaliplatin include SOS lesions (69.35%), fibrosis (50.95%) and steatosis (38%). After scoring of histopathological parameters based on modified criteria according to Rubbia-Brandt et al., they were statistically insignificant between both groups for portal and/or porto-portal fibrosis (59.3% vs 47.4%, respectively) and moderate/severe macrovacuolar steatosis (10.2% vs 26.3%). Similar distribution between groups was shown for surgical hepatitis with „borderline“ statistical significance (23,7% vs 42,1%, p= 0.05). However, there were significant differencies in vascular lesions, particularly for hemorrhagic centrilobular necrosis (10,2% vs 31,5%, p= 0.01) and peliosis (15,2% vs 36,8%, p= 0.04), but were not significant for sinusoidal dilatation and congestion as well as surgical necrosis. Highgrade vascular lesions such as hemorrhagic centrilobular necrosis and peliosis are less frequent in cases of radiofrequency-assisted liver recetions and might be associated with better clinical outcome in these patients.

The Biological and Hematological Effects of Echinacea purpurea L. Roots Extract in the Immunocompromised Rats with Cyclosporine.

Background:The immune system is the body's defense against foreign organisms and harmful chemicals. Cyclosporine A (CsA) is an immunosuppressant drug widely used. Echinacea purpurea root (EPR) extract is used as an immunostimulant plant.Aim of the Work:The present study aimed at evaluation of the EPR effects against the CsA immunosuppressive rat model.Material and Methods:Thirty-two male Wistar albino rats were randomly divided into control, CsA (immunosuppressive models), CsA + EPR (100 mg/kg/day orally), and CsA + EPR (200 mg/kg/day orally). The biological parameters regarding the food consumption were assessed including feed intake (FI), feed efficiency ratio (FER), and body weights (BW). In addition, the splenic specimens were assessed histopathology. The blood was collected for measuring the blood parameters. All the measured parameters were collected and statistically analyzed. The biological results indicated a significant decrease in BW, FI, and FER in rats treated orally with low and high EPR doses as compared to the control group.Results:The results displayed that the CsA induced a significant decrease in red blood cells (RBCs) and white blood cells (WBCs) count. Histopathologically, CsA induced a marked decrease in the cellularity of the white pulp with congested blood sinusoids of the red pulp together with significant depletion of periarteriolar lymphoid sheath. Both the high and low doses of EPR significantly reversed the altered RBCs and WBCs counts. Histopathologically, both the low and high doses of EPR displayed apparently increase in the periarteriolar area together with the persistence of the congestion of the red pulp blood sinusoids compared to CsA group, indicating partial amelioration of the structural changes.Conclusion:In a nutshell, the current findings revealed that EPR extract ameliorated the hematological changes. However, there was a partial correction of the CsA-induced microscopic changes of the rat spleen.

Assessing the Hepatotoxicity of Industrial Leachate; Histopathology and Heavy Metal Contents in Liver of Wistar Rats

The process of paper production requires a huge quantity of water and energy and in turn contributes a number of effluents in the form of phenolics, toxic organic compounds and heavy metals in wastewater (leachate). The present investigation was aimed to assess the toxic effects of leachate on liver micro-architecture and heavy metal elements of the liver. Eighteen (18) healthy male Wistar rats (240 ± 10g) were selected and acclimatized prior to experimental treatment. These rats were randomly divided into three groups viz, Control group (received 4ml/ kg normal saline), Group 1 (4ml/ kg leachate) and Group 2 (4ml/ kg 1:10 diluted leachate). All the animals were dissected and liver tissues were collected and processed accordingly after 24 h of leachate treatment. High level of cadmium and chromium were found in Group 1 as compared to the control group upon liver metal contents analysis found out by flame atomic absorption spectrometer. A clear disruption of micro-architecture of the liver, congested sinusoids, damaged central vein, and perturbed morphology was observed in Group-1 as revealed by H &amp; E staining. Moreover, loss of polarity, congestion, and disruption of hepatocytes and pronounced vacuolization in the cytoplasm was observed in Group 2 compared to control sections. On the basis of above findings, it can be concluded that paper industry leachate is highly toxic and its intraperitoneal injection results in hepatotoxicity that not only affects the hepatic micro-architecture but also results in perturbed liver metal contents. Therefore, proper treatment of such wastewater is required before its disposal.

CCl4 INDUCED LIVER INJURY;

Objectives: Evaluate the mitigating effect of aqueous extract of Ginkgobiloba (GkbE) on liver enzymes and histology in carbon tetrachloride (CCl4) induced liverinjury in albino rat. Study design: Experimental study. Setting and Duration: Animal house,Bhitai Dental and Medical College Mirpurkhas and Agriculture University Tando Jam fromAnimal house from May 2015 - August 2016. Subjects and Methods: Sixty rats were equallydivided into 3 groups Group 1- Controls (0.9% isotonic saline), Group 2- (CCl4 CCl4 1.0mg/kg intraperitoneal) and Group 3- (CCl4+ GkbE). Blood samples were collected at end ofexperiment from tail veins. Liver was obtained after rat sacrifice by cervical dislocation. Tissuewas fixed in formaldehyde and embedded in paraffin. Microscopy of 3μ tissue sections wasperformed after H &amp; E staining. Statistix 10.0 (USA) software was used for data analysisat 95% confidence interval. Results: Four weeks GkbE administration in CCl4 rat showedsignificant amelioration of liver enzymes and improved liver histology (p=0.0001). In GkbEtreated rats, the histological changes of degeneration, fatty change, inflammatory cellinfiltration, sinusoid congestion and necrosis was minimal (p=0.0001). GkbE was provedof mitigating the hepatocellular injury inflicted by carbon tetrachloride. Conclusion: GkbEmitigates the carbon tetrachloride induced liver injury in rat model. GkbE may be used in drugand chemical induced liver injury.

First report of Posthodiplostomum minimum metacercariae and resulting histopathological changes in Bagrus bajad from Lake Nasser, Egypt.

Parasitological studies of 100 Bagrus bajad fish were collected from Lake Nasser, Aswan, Egypt. Out of them 75 were infected with metacercariae in two forms; encysted in most visceral organs and free only in air bladder. These were identified morphologically as Posthodiplostomum minimum metacercariae (Strigeidida: Diplostomidae). The intensity of white grub in B. bajad was high in the intestine (30 encysted metacercariae/g). The highest prevalence season observed in summer and the lowest in winter. The histopathological examination revealed encysted metacercariae of different sizes within the intestinal musculature accompanied with granular infiltration with eosinophilia. Degenerative changes were observed in liver and kidney cells, as well as congestion of hepatic sinusoids. Spleen showed both lymphoid and melanomacrophages cells depletion.

The phytochemical analysis and safety evaluation of ethanol leaf extract of &lt;i&gt;Grewia carpinifolia&lt;/i&gt; in Wistar rat

The traditional use of plants is a common practice globally. Grewia carpinifolia is used in treatment of gastrointestinal disorders and as anti-parasitic. However its toxicity profiles are not well documented. Thus there is a need to identify the phytochemical composition of the plant as well as its toxicity following acute and sub-chronic oral administration. The phytochemical analysis, acute toxicity profile as well as daily feed and water intake, body weight changes, serum biochemical and haematological parameters and histology of vital organs were assessed following a daily single oral administration in a 28-day study. Tannins, saponins, flavonoids, alkaloids, phlobatannins, terpenoids, cardiac glycosides and anthraquinones were present in the extract. The lethal dose (LD50) was greater than 4000 mg/kg. The extract caused significant decrease in water intake in a dose dependent manner, significant increases were observed in liver enzymes analysed (AST, ALP, ALT) at 800 mg/kg after 28-day administration. In addition, congestion of central nucleus and sinusoids were observed in the liver at 800 mg/kg. G. carpinifolia leaf extract appear to be safe at doses below 800 mg/kg body weight. Preliminary results suggest promising alternatives for exploring therapeutic and pharmaceutical interest in G. carpinifolia leaf extract.

Histopathological Profile In Fatal Yellow Phosphorous Poisoning.

Yellow phosphorous (YP) is the toxic form of elemental phosphorous and the chief constituent of firecrackers and rodenticides. In India, the rodenticide paste is frequently used for the suicidal purpose. This study is an autopsy-based observational study which describes the histopathological features of heart, lungs, liver, and kidney of fatal cases of YP poisoning. The most common autopsy features in the viscera were congestion and petechial hemorrhage. The liver histopathology findings were microvesicular steatosis (68%), hepatic necrosis (62%), macrovesicular steatosis (50%), inflammatory cells (46%), sinusoidal congestion (40%), cholestasis (32%), and toxic hepatitis (18%). Hepatic necrosis ranged from being focal to centrizonal in distribution. Congestion was the most common feature observed in the lungs and the kidney. This is the largest autopsy-based study on YP poisoning till date. The histopathological features of liver were consistent with YP poisoning whereas the findings of heart, lungs, and kidney were nonspecific in nature.

Clarithromycin-Induced Acute Liver Failure (ALF)

Clarithromycin is a macrolide antibiotic widely used to treat respiratory, skin, and soft tissue infections. Although elevated liver enzymes and cholestatic hepatitis have been infrequently reported, comprehensive literature review reveals only 6 cases of clarithromycin-induced ALF (fig 2). 60-year-old male with history of hypertension and hypothyroidism presented to the hospital with acute asthma exacerbation secondary to respiratory tract infection. Complete blood picture, and liver and kidney function tests were within normal limits. Clarithromycin, prednisone and albuterol inhaler were prescribed, and he was discharged. 10 days later, he represented and physical examination revealed stable vital data but soft, diffusely tender abdomen with hypoactive bowel sounds and no peritoneal signs. Laboratory analysis revealed WBC=12.2bil/L, hemoglobin(hb)=14.5 g/dL and platelets=129bil/L, lipase=33 U/L, lactic acid=0.6 mmol/L, ammonia=22 mcmol/L and normal coagulation profile. Figure 1 highlights the trend of liver function tests (LFTs) during hospitalization. CT of the abdomen with contrast, abdominal ultrasound with doppler and echocardiography were all normal. Viral hepatitis panel (anti-HAV, anti-HBs, anti-HBc, HBs antigen, anti-HCV, HCV-RNA, & anti-HEV), autoimmune hepatitis panel (ANA, AMA, smooth muscle antibody, liver-kidney microsomal antibody, and total immunoglobulin) and atypical viruses (HIV, CMV, and HSV) were insignificant. On third day, he developed altered mental status; Hb dropped to 5.5 g/dL, platelets dropped to 35 bil/L and LFTs worsened. Liver biopsy was canceled due to hemodynamic instability and coagulopathy. Massive transfusion was initiated, but despite aggressive resuscitation, the patient had cardiac arrest and expired. On autopsy, histopathologic analysis of the liver revealed diffuse hepatocellular necrosis with occasional sparing of periportal hepatocytes (fig 3) consistent with the prior reported cases and the pattern of idiosyncratic drug induced liver injury (DILI). There was no evident lobular or portal inflammation, fibrosis, viral cytopathic effect, thromboemboli, or malignancy.2304_A Figure 1. Trend of liver function testsProminent eosinophils in the portal tract or lobules can suggest a drug-induced hypersensitivity reaction but are rarely seen in cases of idiosyncratic drug reactions. There are no defined pathognomonic histopathologic findings of DILI and a high index of clinical suspicion in combination with histopathologic findings are needed for the diagnosis.2304_B Figure 2. Reported cases of acute liver failure from Clarithromycin2304_C Figure 3. A: Low power photomicrograph of H&E section of liver showing geographic areas of necrosis and marked sinusoidal congestion. B: High power photomicrograph of H&E stain of liver showing a central vein (*) with adjacent marked sinusoidal congestion and extensive hepatocyte necrosis.

Seed and bark extracts of Acacia catechu protects liver from acetaminophen induced hepatotoxicity by modulating oxidative stress, antioxidant enzymes and liver function enzymes in Wistar rat model.

In this study we investigated the hepatoprotective effects and possible mechanism of Acacia catechu in acetaminophen (APAP) induced hepatotoxicity using female Wistar rat model. Hepatotoxicity was induced by oral administration of acetaminophen (750 mg/kg body weight) for 24 h. The seed (400 mg/kg body weight) and bark (400 mg/kg body weight) extract's treated groups exhibited hepatoprotective effects and was compared with well-known clinical anti-dote N-acetylcysteine (NAC). When groups treated with acetaminophen, significant increase of liver weight/body weight ratio, liver function enzymes such as alanine aminotransferase (ALT), alkaline phosphatase (ALP) and aspartate aminotransferase (AST) and decrease of antioxidant enzymes such as glutathione (GSH) and superoxide dismutase (SOD) were observed. The histopathology of APAP treated groups also showed moderate degree of sinusoidal congestion, centrilobular necrosis with polymorph nuclear cells infiltration, marked vacuolations and congestion. However, pretreatment with seed or bark extract groups decreased LPO accumulation, reduced the liver function enzymes and increased antioxidant defense enzymes. Moreover, histopathology of seed extract treated groups showed normal architecture whereas bark extract treated groups exhibited mild degree of vacuolations in the hepatocytes with minimal sinusoidal congestion. Taken together, our study concludes that A. catechu seed extract to be a more promising agent for protecting liver from APAP induced hepatotoxicity.