bicyclol and Hepatitis

To evaluate the therapeutic effects of bicyclol combined with ganciclocir on infantile cytomegalovirus hepatitis.. Seventy infants with cytomegalovirus hepatitis were randomized into treatment group (n=35) and control group (n=35) for a 2-week-long treatment with ganciclocir (5 mg/kg) with and without oral bicyclol (3 mg/kg, twice daily), respectively.. In both groups, significant changes occurred in the levels of alanine aminotransferase, alkaline phosphatase, serum total bilirubin, serum total bile acid, and glutamyl transpeptidase after the 2-week treatment (P<0.01); these parameters differed significantly between the two groups after the treatment (P<0.01). Compared with those in the control group, the infants in the treatment group showed significantly better responses to the treatment (P<0.05) with a significantly higher rate of serum anti CMV IgM negativity (P<0.05).. Bicyclol combined with ganciclocir can reduce glutamic pyruvic transaminase, alkaline phosphatase and serum total bilirubin, and decrease bile acid levels to lessen liver cell damage and promote the recovery of liver cells.

Topics: Alanine Transaminase; Alkaline Phosphatase; Antiviral Agents; Bilirubin; Biphenyl Compounds; Cytomegalovirus; Cytomegalovirus Infections; Drug Therapy, Combination; Ganciclovir; Hepatitis; Humans; Infant; Liver Function Tests

Pembrolizumab, an anti-programmed cell death protein 1 (PD-1) antibody, has been shown to improve survival in patients with non-small cell lung cancer (NSCLC) with high expression of programmed death-ligand 1 (PD-L1). Corticosteroids are the mainstay for most high-grade immune-related adverse events (irAEs) such as pembrolizumab-induced hepatitis. However, the dose and duration of corticosteroid therapy are not well defined. The objective of this case report was to describe a new treatment pattern for severe immune checkpoint inhibitor-associated hepatitis. Here, we report the case of a patient with metastatic lung adenocarcinoma who developed grade 3 immunotherapy-induced hepatitis after the first cycle of pembrolizumab. Alanine aminotransferase (ALT) levels peaked at 233 U/L. Hepatitis was alleviated after the administration of methylprednisolone. Therefore, we retreated the patient with pembrolizumab. However, aminotransferase levels increased again after the initiation of low-dose methylprednisolone or the reuse of pembrolizumab. Finally, hepatitis was controlled with low-dose methylprednisolone plus bicyclol, a Chinese hepatoprotective agent. Although the patient had been on low-dose methylprednisolone therapy for about six months, he showed a prompt response. During this period, we also found a dramatic decrease in the neutrophil-lymphocyte ratio (NLR), senescent T cells (CD8

Topics: Aged; Anti-Inflammatory Agents; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Immunological; Biphenyl Compounds; Carcinoma, Non-Small-Cell Lung; Dose-Response Relationship, Drug; Drug Combinations; Hepatitis; Humans; Lung Neoplasms; Male; Methylprednisolone; Prognosis

The interactions of bifendate (DDB) or analogs (Bicyclol, I, II and III) with catalase are analyzed by spectrophotometric methods. The fluorescence spectra results show the intrinsic fluorescence of catalase is strongly quenched by DDB or analogs with a static quenching procedure. The binding constants are obtained at three temperatures. The thermodynamics parameters (ΔH, ΔS, ΔG) indicate the hydrophobic and electrostatic interactions play a major role in the interaction. The results of synchronous fluorescence, UV-vis absorption and three-dimensional fluorescence spectra demonstrate that the microenvironments of Trp residue of catalase are disturbed by the analogs. Thermodynamic results showed that DDB is the strongest quencher and bind to catalase with the highest affinity among five compounds.

Topics: Animals; Antiviral Agents; Binding Sites; Biphenyl Compounds; Catalase; Cattle; Hepatitis; Liver; Spectrometry, Fluorescence; Thermodynamics

To assess the anti-invasion effect of bicyclol (1) and its mechanism in human hepatocellular carcinoma (HCC) MHCC97-H cells with high metastatic potential. MTT assay was performed to evaluate the cytotoxicity of 1 to MHCC97-H cells and its inhibitory effect on the adhesion of these cells to laminin (LN) and fibronectin (FN). The anti-invasion effect of 1 was detected in an experiment using a transwell chamber. Transcription of vascular endothelial growth factor (VEGF), nm23-H1, and urokinase-type plasminogen activator receptor (uPAR) mRNAs was determined by an RT-PCR assay. The secretion and expression of alpha-fetoprotein (AFP) were analyzed by ELISA and flow cytometry, respectively. At concentrations of 10, 50, and 100 mumol/l, 1 obviously inhibited the adhesion of the MHCC97-H cells to LN and FN. The rates of inhibition of MHCC97-H cell invasion by 50 and 100 mumol/l for 1 were 37.3 and 50.2%, respectively. Drug 1 also decreased the expressions of VEGF, nm23-H1, and uPAR mRNA and the secretion of AFP in MHCC97-H cells. At low cytotoxic concentrations, the anti-hepatitis drug 1 demonstrated a significant anti-invasive effect in human HCC MHCC97-H cells with high metastatic potential. The inhibition of the expressions of VEGF, nm23-H1, and uPAR should contribute, at least in part, to the anti-invasion property of 1.

Topics: alpha-Fetoproteins; Biphenyl Compounds; Carcinoma, Hepatocellular; Cell Adhesion; Hepatitis; Humans; Liver Neoplasms; Molecular Structure; Neoplasm Invasiveness; Neoplasm Metastasis; Sequence Homology, Nucleic Acid; Tumor Cells, Cultured; Urokinase-Type Plasminogen Activator; Vascular Endothelial Growth Factor A

Heat shock proteins (HSPs) are the best-known endogenous factors that protect against cell injury under various pathological conditions and that can be induced by various physical, chemical, and biological stressors. New research seeks to discover a compound that is clinically safe and can induce the accumulation of HSPs in patients. This paper reports that the oral administration of three doses of bicyclol, a novel antihepatitis drug, induced hepatic HSP27 and HSP70 expression in a time- and dose-dependent manner, and that bicyclol treatment stimulated heat shock factor 1 (HSF1) activation in mice. The inducing effects of bicyclol on HSP27, HSP70 and HSF1 were all blocked by quercetin, an inhibitor of HSP biosynthesis. The cytoprotective effect of HSP27/70 induced by bicyclol against hepatotoxicity of acetaminophen (AP) was assessed in mice. The prior administration of bicyclol markedly suppressed AP-induced liver injury as indicated by the reduction in the elevation of serum alanine aminotransferase and aspartate aminotransferase, in liver necrosis, in the release of cytochrome c and apoptosis-inducing factor from mitochondria, as well as in hepatic deoxyribonucleic acid fragmentation in mice. However, all the above actions of bicyclol against AP-induced mouse liver injuries were significantly attenuated by quercetin. This is the first report to show that bicyclol induces hepatic HSP27/70 expression via activation of HSF1 and that the cytoprotective action of bicyclol against liver injury is mediated by its induction of HSP27/70. These results provide new evidence for elucidating the mechanism of the hepatoprotective action of bicyclol in animals and patients.

Topics: Animals; Antioxidants; Biphenyl Compounds; Cytoprotection; DNA-Binding Proteins; Heat Shock Transcription Factors; Heat-Shock Proteins; Hepatitis; HSP27 Heat-Shock Proteins; HSP70 Heat-Shock Proteins; Liver; Male; Mice; Quercetin; Transcription Factors

To study the toxicity of bicyclol to animals.. Acute toxicity test was performed in Kunming strain mice that were orally given bicyclol at the doses of 3 and 5 g/kg body weight, respectively. Wistar rats were orally administered bicyclol at a dose of 5 g/kg body weight. Death and clinical symptoms of animals were recorded within 7 d. Sub-acute toxicity test was carried out in rats that were treated with various doses of bicyclol (150, 300, 600 mg/kg) once daily for 14 d. Animal behaviors, blood biochemical markers, blood and urine pictures were examined. Chronic toxicity test was conducted in 80 Wistar rats of both sexes. The animals were orally administered with various doses of bicyclol (150, 300, 600 mg/kg, 100-400 folds corresponding to the proposed therapeutic dose (1.5 mg/(kg.d)) of bicyclol for patients) once daily for 6 mo except for Sunday. The control group was given the same volume of 0.2% sodium carboxyl methylcellulose (Na-CMC). Twenty-one beagle dogs received bicyclol (25, 75, 225 mg/kg, 16.6, 50, 150 folds corresponding to the proposed therapeutic dose of bicyclol for patients) once a day for 6 mo except for Sunday. The body weight, food intake, urine and feces, blood picture, blood biochemical markers, and pathological examination of main organs were determined. Mutagenicity and teratogenicity were determined. Mutagenicity assay included Ames's test, chromosome aberration test in CHL cells and micronucleus test in mice. For the teratogenicity assay, pregnant Wistar rats weighing 200-250 g were treated with 0.2, 1.0 g/kg bicyclol once daily from the 7th d of gestation for 10 d.. The oral LD(50) of bicyclol was over 5 g/kg in mice and rats. No noticeable alterations in subacute and chronic toxicity of rats and dogs were demonstrated. No mutagenicity and teratogenicity of bicyclol were found.. Bicyclol has no detectable chronic toxicity as well as mutagenicity and teratogenicity in animals.

Topics: Animals; Biphenyl Compounds; Chromosome Aberrations; Dogs; Drug Evaluation, Preclinical; Female; Hepatitis; Injections, Subcutaneous; Male; Mice; Mice, Inbred Strains; Mutagenicity Tests; Rats; Rats, Wistar; Teratogens