Changes in Biochemical Parameters, Antioxidative Enzymes and Histopathology of Liver Induced by Cadmium (Cd) and Chlorpyrifos (CPF) in Wistar Rats

Background: Cd and CPF intoxication may occur directly through drinking water. Since the population tend to receive combination of multiple intoxicants through environment contamination, there is need for conducting studies to assess the impact of individual and combined environmental pollutants. The present research work was designed to study hepatotoxicity induced by Cd, CPF and their combination.Methods: The experiment was carried out for 28 days in Wistar rats. G1: Control. G-2:CdCl2 @ 22.5mg/ kg b.wt / oral. G3: CPF @ 25 mg/ kg b.wt /per oral. G4:[email protected] mg + CPF @ 25 mg/ kg b.wt /per oral. Biochemical parameters ware estimated from serum and liver samples were processed for tissue antioxidative parameters and histopathological examination. Result: Higher mean values of AST, ALT, ALP and lower liver GSH and SOD were observed in G2, 3 and 4 on 15th and 29th day when compared with G1. Liver in G2 and 3 showed mild degenerative changes, areas of necrosis and loss of architecture. In G4, lesions were moderate in severity. In addition, moderate perivascular fibrosis of portal triad was observed. The effects in combined group were severe than individual groups due to synergistic action of the combined pollutants.

Histological quantification of decomposed human livers: a potential aid for estimation of the post-mortem interval?

The objective of this study was to determine if a novel scoring-based model for histological quantification of decomposed human livers could improve the precision of post-mortem interval (PMI) estimation for bodies from an indoor setting. The hepatic decomposition score (HDS) system created consists of five liver scores (HDS markers): cell nuclei and cell structure of hepatocytes, bile ducts, portal triad, and architecture. A total of 236 forensic autopsy cases were divided into a training dataset (n = 158) and a validation dataset (n = 78). All cases were also scored using the total body score (TBS) method. We specified a stochastic relationship between the log-transformed accumulated degree-days (log10ADD) and the taphonomic findings, using a multivariate regression model to compute the likelihood function. Three models were applied, based on (i) five HDS markers, (ii) three partial body scores (head, trunk, limbs), or (iii) a combination of the two. The predicted log10ADD was compared with the true log10ADD for each case. The fitted models performed equally well in the training dataset and the validation dataset. The model comprising both scoring methods had somewhat better precision than either method separately. Our results indicated that the HDS system was statistically robust. Combining the HDS markers with the partial body scores resulted in a better representation of the decomposition process and might improve PMI estimation of decomposed human remains.

Administration of Human MSC-Derived Extracellular Vesicles for the Treatment of Primary Sclerosing Cholangitis: Preclinical Data in MDR2 Knockout Mice

Primary Sclerosing Cholangitis (PSC) is a progressive liver disease for which there is no effective medical therapy. PSC belongs to the family of immune-mediated biliary disorders and it is characterized by persistent biliary inflammation and fibrosis. Here, we explored the possibility of using extracellular vesicles (EVs) derived from human, bone marrow mesenchymal stromal cells (MSCs) to target liver inflammation and reduce fibrosis in a mouse model of PSC. Five-week-old male FVB.129P2-Abcb4tm1Bor mice were intraperitoneally injected with either 100 µL of EVs (± 9.1 × 109 particles/mL) or PBS, once a week, for three consecutive weeks. One week after the last injection, mice were sacrificed and liver and blood collected for flow cytometry analysis and transaminase quantification. In FVB.129P2-Abcb4tm1Bor mice, EV administration resulted in reduced serum levels of alkaline phosphatase (ALP), bile acid (BA), and alanine aminotransferase (ALT), as well as in decreased liver fibrosis. Mechanistically, we observed that EVs reduce liver accumulation of both granulocytes and T cells and dampen VCAM-1 expression. Further analysis revealed that the therapeutic effect of EVs is accompanied by the inhibition of NFkB activation in proximity of the portal triad. Our pre-clinical experiments suggest that EVs isolated from MSCs may represent an effective therapeutic strategy to treat patients suffering from PSC.

Histomorphological changes in various rat tissues following chronic exposure to copper-zinc-pyrite ore

Aim. To assess the histomorphological state of lung, gastrointestinal and kidney tissues following exposure to copper-zinc-pyrite ore in the long-term model experiment. Methods. The study was performed on 60 outbred albino male rats, aged 34 months, weighting 20030 g. The toxic effect of heavy metal salts of copper-zinc-pyrite ore on the animal's body was analyzed by the model of dosed oral injection of water with ore in a dose 600 mg/kg body weight for 120 days. Pieces of the stomach, small and colon, liver, lungs and kidneys were taken from control and experimental rats for histomorphological study on the 30th, 60th, 90th and 120th day of the experiment. Results. The structural disorders of the stomach lining were observed on the 30th day of the experiment: desquamated and dilapidated epithelial cells appeared in the preparations. On the 120th day, along with signs of epithelial desquamation and diffuse lymphocytic infiltration, the preparations contained large lymphoid follicles that occupy the full thickness of the gastric mucosa. The epithelial layer of the small intestine mucosa was disrupted on the 60th day. At day 120 diffuse infiltration and necrotic changes in the lining of the small intestine were recorded. Lymphomacrophagia infiltrations were observed during portal triad and inside the liver wedges of experimental animals on the 30th day of the experiment. By the end of the experiment, toxic hepatocyte dystrophy developed. On the 60th day, signs of bronchopneumonia appeared in the lung tissue. After 3 months, tubulopathy and tubulointerstitial nephritis were observed in the experimental animals. Conclusion. Prolonged administration of ore has led to pronounced inflammation and degenerative changes in the gastrointestinal tract, liver, kidney and lung tissues, accompanied by lymphocytic tissue reaction.

Early surgical management of severe liver trauma with vascular complication can lead to early discharge

Intrahepatic arterio-portal fistulas are rare complications of blunt hepatic trauma. We describe a case of a 35-year-old male sustaining blunt abdominal trauma resulting in a grade IV liver injury complicated by arterio-portal fistula, portal venous pseudoaneurysm and concomitant bile duct injury. Although arterial embolisation is the mainstay of treatment for arterio-portal fistula, we describe a rationale for early involvement of a hepatobiliary surgeon for multidisciplinary management. Hepatic resection for acute hepatic trauma can, in selected cases, promptly manage all elements of portal triad injury, and in this particular case facilitated early uncomplicated discharge.

Histogenesis of human fetal liver from 12 weeks to 36 weeks of gestation

Background: Fetal human liver developmental morphology is very important for diagnosis of congenital anomalies. The development of human liver is an ongoing process which begins after fertilization and continues into post-natal life. Liver is one of the organs of gastrointestinal tract having both exocrine and endocrine functions and capable of regeneration. Not only adult liver, the fetal liver is also an important organ with Haemopoietic functions. Pediatric liver transplants accounting for 10-15% of all liver transplants worldwide occur due to congenital defects.Methods: The study is conducted on 50 livers procured from 50 aborted fetuses (34 males and 16 females) ranging from 12 to 36 weeks of gestation .After confirming their age through CRL they were grouped. Then processed to form sections and stained with hematoxylin and eosin and seen under light microscope.Results: Histogenesis and development of human liver in prenatal period was observed under the microscope at various gestational age groups which was confirmed with lobular pattern, portal triad structures ,central vein and sinusoids showing fetal haemopoietic function which regress towards the term.Conclusions: The present study gave emphasis on all physical parameters and a detail histogenesis and development of human liver in prenatal period from 12 to 36 weeks of gestation. This work agreed with previous studies.

Renalase Attenuates Mouse Fatty Liver Ischemia/Reperfusion Injury through Mitigating Oxidative Stress and Mitochondrial Damage via Activating SIRT1

Liver ischemia/reperfusion (IR) injury is a severe complication of liver surgery. Moreover, nonalcoholic fatty liver disease (NAFLD) patients are particularly vulnerable to IR injury, with higher rates of postoperative morbidity and mortality after liver surgeries. Our previous study found that renalase (RNLS) was highly sensitive and responsive to oxidative stress, which may be a promising biomarker for the evaluation of the severity of liver IR injury. However, the role of RNLS in liver IR injury remains unclear. In the present study, we intensively explored the role and mechanism of RNLS in fatty liver IR injury in vivo and in vitro. C57BL/6 mice were divided into 2 groups feeding with high-fat diet (HFD) and control diet (CD), respectively. After 20 weeks’ feeding, they were suffered from portal triad blockage and reflow to induce liver IR injury. Additionally, oleic acid (OA) and tert-butyl hydroperoxide (t-BHP) were used in vitro to induce steatotic hepatocytes and to simulate ROS burst and mimic cellular oxidative stress following portal triad blockage and reflow, respectively. Our data showed that RNLS was downregulated in fatty livers, and RNLS administration effectively attenuated IR injury by reducing ROS production and improving mitochondrial function through activating SIRT1. Additionally, the downregulation of RNLS in the fatty liver was mediated by a decrease of signal transduction and activator of transcription 3 (STAT3) expression under HFD conditions. These findings make RNLS a promising therapeutic strategy for the attenuation of liver IR injury.