Biochemical and Histopathological Alterations in Different Tissues of Rats Due to Repeated Oral Dose Toxicity of Cymoxanil

Evaluating potential adverse health impacts caused by pesticides is an important parameter in human toxicity. This study focuses on the importance of subchronic toxicity assessment of cymoxanil fungicide in rats with special reference to target biochemical enzymes and histopathological changes in different tissues. In this regard, a 21-day toxicity study with repeated cymoxanil oral doses was conducted. It has been shown that low doses (0.5 mg/kg) were less effective than medium (1 mg/kg) and high (2 mg/kg) doses. Moreover, high dose dose-treated rats showed piecemeal necrosis in the liver, interstitial nephritis and tubular degeneration in the kidneys, interstitial pneumonia and type II pneumocyte hyperplasia in the lungs, gliosis, spongiosis, and malacia in the brain, and testicular edema and degeneration in the testes. Cymoxanil significantly increased AST, ALT, and ALP in serum and liver, indicating tissue necrosis and possible leakage of these enzymes into the bloodstream. Creatinine levels increased, indicating renal damage. Similarly, significant inhibition was recorded in brain acetylcholinesterase, indicating that both synaptic transmission and nerve conduction were affected. Importantly, these histopathological and biochemical alterations were dose-dependent. Taken together, our study reported interesting biochemical and histopathological alterations in different rat tissues following repeated toxicity with oral doses of cymoxanil. Our study suggests future studies on different pesticides at different concentrations that would help urge governments to create more restrictive regulations concerning these compounds’ levels.

A Novel Hepadnavirus is Associated with Chronic Hepatitis and Hepatocellular Carcinoma in Cats

In 2015, over 850,000 people died from chronic hepatitis and hepatocellular carcinoma (HCC) caused by hepatitis B virus (HBV). A novel hepatitis B-like virus has recently been identified in domestic cats. The pathogenic potential of domestic cat hepadnavirus (DCH), for which 6.5% to 10.8% of pet cats are viremic, is unknown. We evaluated stored formalin-fixed, paraffin-embedded biopsies of diseased and normal feline liver for the presence of DCH using PCR and in situ hybridization (ISH). DCH was detected in 43% (6/14) of chronic hepatitis cases and 28% (8/29) of HCCs, whereas cholangitis (n = 6), biliary carcinoma (n = 18) and normal liver (n = 15) all tested negative for DCH. Furthermore, in DCH-associated cases, the histologic features of inflammation and neoplasia, and the viral distribution on ISH were strikingly similar to those seen with HBV-associated disease. Several histological features common in human HBV-associated hepatitis, including piecemeal necrosis and apoptotic bodies, were identified in DCH-positive cases of chronic hepatitis. In two cases of HCC examined, the proliferation index in regions that were ISH-positive was higher than in ISH-negative regions. The intracellular distribution of virus in both hepatitis and HCC demonstrated that viral nucleic acid is present in both nuclear and cytoplasmic forms. Collectively, these findings demonstrate a compelling association between DCH and some cases of chronic hepatitis and hepatocellular carcinoma in the cat that mirrors features of HBV-associated hepatopathies. Future investigations of viral epidemiology and natural history are needed to establish the impact of DCH on feline health.

Sub-chronic hepatotoxicity test of Plantago mayor L. extract

The aim of this study was to examine hepatotoxicity of Plantago mayor L. extract on rat by using effective dosage. By experimental study and post test only with control group design. 15 rats (Rattus norvegicus) were divided in to 3 group. Group A as a natural control was given aquades. Group B and C were given extract of Plantago major L. 50mg, and 100mg/200g BW rat/day per oral. Liver function was determined with measurement of Aspartate aminotransferase (AST) level, Alanine aminotransferase (ALT), total bilirubin, and histopathological feature of liver. Blood sampling and Liver organ were taken after 28 days of intervention. The average of AST levels, ALT and total bilirubin among groups A, B and C were AST levels (145.40±52.92, 129.00±34.89, and 115.60±13.24 U/l), ALT (76.40±18.87, 83.20±18.71, and 61.00±8.45 U/l) and total bilirubin (0.56±0.03, 0.77±0.22, and 0.58±0.08 mg/dL). Statistical analysis showed that there were not significantly differences of AST levels (p=0,63; CI95%), ALT (p=0,47; CI95%) and total bilirubin (p=0,0,09; CI95%) between the groups. In histopathological features, the average Scheuer score between groups A, B and C is 1.79 ± 0.74, 3.30 ± 0.66 and 2.84 ± 0.77. There is a significant difference in Scheuer scores between the groups (p=0,005; CI95%) that show that there is a difference in the effect of giving extract of Plantago major L. to hepatocyte cells leading to a piecemeal necrosis. This study can be concluded that in effective dosage, Plantago major L. extract able to induce hepatocytes injury although it cannot cause liver disfunction yet.

Childhood B-Precursor-ALL Presenting as Hepatitis - A Diagnostic and Therapeutic Challenge

Abstract 4331 Liver involvement in childhood acute lymphoblastic leukemia (ALL) at presentation is common with hepatomegaly but severe impairment or hepatitis is rare with only 9 reported cases. The need to start anti-leukemic treatment despite the potential hazard of severe liver failure poses a clinical dilemma. We report a 6 year old girl who presented with jaundice, fever, vomiting and diarrhoea, cytopenia, hyperbilirubinemia of 5.7 mg/dl (direct 5.2), ASAT of 3389, ALAT of 2747 U/L, increased INR to 1.33, but normal ammonia. An acute common-ALL was diagnosed and serology, PCR-studies and cultures were negative for viruses causing hepatitis. Liver biopsy revealed diffuse hepatic blast infiltration, piecemeal necrosis and hepatocellular cholestasis without signs of infectious hepatitis. We treated the patient according to the ALL-BFM-2000-protocol without dose reductions and on day 8, hyperbilirubinemia had completely normalized and liver enzymes had significantly decreased. Further therapy was uneventful and the patient is alive and well 12 month after diagnosis, without any signs of hepatic dysfunction. Reviewing the literature on children with ALL presenting with hepatitis revealed 9 patients with a mean age of 8.8 years (range 4 to 15), female to male ratio of 2.0 and precursor B-cell immunophenotype in 8/9 patients. Patients had a mean bilirubin of 8.7 mg/dl (range 2 – 16.5), 3 had highly elevated transaminases above 2000 U/L, and two of them died initially. Another patient with moderately increased liver enzymes but hepatic encephalopathy needed transient hemofiltration, but survived. In none of the reported cases a viral organism has been identified and abnormal liver function normalized during chemotherapy in most of the patients. This indicates, that leukemia rather than infection was responsible for hepatitis. In conclusion, severe hepatitis in children with ALL is rare, seems to affect the older girl, and highly elevated liver enzymes are associated with early death. After infective organisms have been excluded, instant start of an effective induction therapy is required, even despite severe hepatitis, most probably caused by blast infiltration. Disclosures: No relevant conflicts of interest to declare.