Histomorphometric study of rat liver during the treatment of the acute toxic injury

Introduction. There are a few effective therapies are available for acute liver injury at present. The aim of the study was to investigate histological and morphometric changes in the liver using models of toxic damage caused by carbon tetrachloride (CCl4 ) and acetaminophen during correction with Oxymethyluracil (OMU). Material and methods. A total of ninety rats were divided into 18 groups. The treatment of acute liver damage models caused by a single injection of CCl4 or acetaminophen was carried out using “Heptor”, “Mexidol”, and OMU. The correction was carried out twice (sacrificed 24 hours after intoxication) and four times (sacrificed 72 hours after intoxication). Liver tissues were processed using standard histological techniques (H&E). A semi-quantitative assessment was performed using a scale based on the severity of liver cell deaths. Results. Twenty-four hours after administration of CCl4 or 72 hours after administration of acetaminophen, the treatment with OMU led to a decrease in liver cell death compared to the group with administration of only CCl4 or acetaminophen. Seventy-two hours after CCl4 and 24 hours after acetaminophen intoxication, these groups with the OMU treatment did not differ from those of the carbon tetrachloride- or acetaminophen-induced liver injury groups, respectively. Conclusion. Thus, on the model of CCl4 liver injury, the treatment with OMU is more effective for 24 hours. In the case of acetaminophen intoxication, the effectiveness of treatment with OMU is better for 72 hours. The results obtained are possibly associated with a different mechanism of the damaging effect of the studied toxicants.

14-Day Repeated Intraperitoneal Toxicity Test of Ivermectin Microemulsion Injection in Wistar Rats

To evaluate the safety of ivermectin microemulsion injection, 100 Wistar rats were injected intraperitoneally at 0.38 g/kg, 0.19 g/kg, and 0.1 g/kg for 14 days. The 14-day repeated toxicity test of ivermectin microemulsion injection was systematically evaluated by clinical observation, organ coefficient, hematological examination, clinical chemistry examination, and histopathological examination. The results showed that no rats died during the test. At the initial stage of treatment, the rats in the high dose group had mild clinical reaction, which disappeared after 4 days. Clinical chemistry showed that the high dose of ivermectin microemulsion could cause significant changes in ALT and LDH parameters in male rats; high and medium doses could increase the liver coefficients of male and female rats. The toxic target organ may be the liver as indicated by histopathological findings. No significant toxic injury was found in the heart, liver, spleen, lung, kidney, brain, ovary, and testes of all groups of rats. No drug-related toxic effects were found at low doses, and thus the NOVEL of ivermectin microemulsion injection was 0.19 g/kg.

Preventive Effects of Three Polysaccharides on the Oxidative Stress Induced by Acrylamide in a Saccharomyces cerevisiae Model

Saccharomyces cerevisiae was used as a model to explore the preventive effect of two marine polysaccharides separately derived from Sepia esculenta ink (SIP) and Laminaria japonica (FL) as well as one terrestrial polysaccharides from Eleocharis tuberosa peel (WCPP) on toxic injury induced by acrylamide (AA). The growth of yeast was evaluated by kinetics indexes including doubling time, lag phase and maximum proliferation density. Meanwhile, intracellular redox state was determined by contents of MDA and GSH, and SOD activity. The results showed that AA inhibited yeast growth and destroyed the antioxidant defense system. Supplement with polysaccharides, the oxidative damage of cells was alleviated. According to the growth recovery of yeast, FL and WCPP had similar degree of capacity against AA associated cytotoxicity, while SIP was 1.5~2 folds as strong as FL and WCPP. SIP and FL significantly reduced production of MDA by AA administration. Moreover, SIP, FL and WCPP increased SOD activity and repressed GSH depletion caused by AA.

Histology of Liver of the Deceased Due to Harmful Use of Alcohol

Aim To study types and incidence of histological changes in liver of people deceased due to harmful use of alcohol. Methods A retrospective review of medico-legal autopsy of 236 adults who died in the years 2015–2016 due to harmful use of alcohol was done. Histopathological liver samples taken during autopsies were evaluated. Blood alcohol content was analyzed. Serological tests for hepatitis B surface antigen and anti-hepatitis C virus (HCV) were performed. Results The most common liver pathology (83.1%) was steatosis, mainly mixed type (50%); 66.9% had high-grade steatosis. Liver fibrosis was detected in 39.4% of cases, with fibrosis of higher than or equal to third grade in 14%, hepatitis in 44.5% and steatohepatitis in 19.1%. Toxic hepatocyte injury features (ballooning degeneration, Mallory–Denk bodies) were found in 20.8% cases and degenerative-damage changes in 41.1%. The correlation between the grade of steatosis and fibrosis (P = 0.0005), toxic injury (0.00000101) and degenerative–traumatic changes (P = 0.00000741) was found. The correlation was found between hepatitis and higher than or equal to third grade steatosis (P = 0.037), cholestasis (P = 0.0139), toxic injury features (P = 2.58 × 10−13), degenerative–damage changes (P = 7.9 × 10−12) and presence of anti-HCV (P = 0.00723) and between progression of fibrosis and presence of toxic injury features (2.28 × 10−19), degenerative–damage changes (P = 4.25 × 10−11) and anti-HCV (P = 0.0263). Conclusions Spectrum of histopathological liver changes is broad regardless of sex, and various traits are present in various patterns. Comorbidities have strong influence on the picture of changes in the liver. Exact evaluation how often and what histopathological changes will develop in alcohol liver disease is not possible by reason of variability of external factors.

Drug Toxicity Evaluation Based on Organ-on-a-chip Technology: A Review

Organ-on-a-chip academic research is in its blossom. Drug toxicity evaluation is a promising area in which organ-on-a-chip technology can apply. A unique advantage of organ-on-a-chip is the ability to integrate drug metabolism and drug toxic processes in a single device, which facilitates evaluation of toxicity of drug metabolites. Human organ-on-a-chip has been fabricated and used to assess drug toxicity with data correlation with the clinical trial. In this review, we introduced the microfluidic chip models of liver, kidney, heart, nerve, and other organs and multiple organs, highlighting the application of these models in drug toxicity detection. Some biomarkers of toxic injury that have been used in organ chip platforms or have potential for use on organ chip platforms are summarized. Finally, we discussed the goals and future directions for drug toxicity evaluation based on organ-on-a-chip technology.

Neutrophil Gelatinase-associated Lipocalin (NGAL) a Promising Biomarker for Early Detection of Nephrotoxic Injury

Renal toxic injury can neither be predicted nor quantified exactly by the serum creatinine level. NGAL is a promising biomarker for early detection of AKI due to different causes. Our objective was to evaluate it�s value in the setting of nephrotoxic injury. We performed an experiment in which we administered gentamicin, atropine and fipronil at different doses to the laboratory mice to quantify the evolution of creatinine and NGAL. Compared to creatinine, NGAL increased faster and was detected at elevated levels from the first 4 h after administration of both low and high dose gentamicin. Fipronil, atropine and the combination caused a significant increase in NGAL serum values at 4 hours, an increase that lasted up to 24 and 72 h , respectively, compared to the control group, Its highest levels were recorded at 4 h. Compared to creatinine, NGAL increased faster and was detected at elevated levels from the first 4 h after administration of fipronil, atropine and the combination of them.