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Open access

Sylwia Tobólska, Sylwia Terpiłowska, Jerzy Jaroszewski and Andrzej Krzysztof Siwicki

Abstract

Introduction

Inosine pranobex (Isoprinosine) stimulates cell-mediated immune responses to viral infections in humans and might have also therapeutic use in animals. The aim of this study was to compare three in vitro cytotoxicity assays on mouse embryo fibroblasts and liver cancer cells and determine their ability to detect early cytotoxic effects for inosine pranobex.

Material and Methods

BALB/3T3 clone A31and HepG2 cells were incubated with inosine pranobex at concentrations from 0.1 to 1,000 μg/mL. Cell viability was determined with the MTT reduction, the LHD release, and the NRU tests.

Results

A decrease in the cell viability was observed after incubating the BALB/3T3 clone A31and HepG2 cells with inosine pranobex.

Conclusions

Based on the cytotoxicity endpoints measured in these investigations in BALB/3T3 clone A31cells, it can be concluded that the cell membrane may be the first part of the cell to be affected by inosine pranobex. The disintegration of lysosomes and mitochondria follows mitochondria damage. In HepG2 cells likewise, the cell membrane may be the first part of the cell to be affected by inosine pranobex. Also in liver cancer cells, the disintegration of mitochondria (assessed with the MTT reduction assay) and next of lysosomes (assessed with the NRU assay) follows mitochondria damage.

Open access

Monika Marczak, Krystyna Marta Okoniewska, Jakub Okoniewski, Tomasz Grabowski and Jerzy Jan Jaroszewski

Abstract

The aim of this study was to determine the correlation between lipophilicity and maximum residue limit (MRL) value specified for veterinary drugs in the fatty tissue of various animal species. The analysis was performed on a group of 73 compounds with different modes of action and MRL values determined for the fatty tissue of animals. Additionally, the logarithm of water/organic phase partition ratio (LogP) and the ratio of ionised and unionised substance in buffer with pH 7.4 (LogD7.4) were calculated. The main analysis was performed after the division of the whole group into six fractions. The linear correlation and regression analysis were used to determine the indirect relationship between the mean arithmetic value of LogP or LogD7.4 in selected fractions and related LogMRL of the drugs tested. The calculations revealed a linear correlation between fractioned lipophilicity and LogMRL values for the analysed compounds. The existence of indirect relationship between lipophilicity and MRL values determined for fatty tissue was confirmed.

Open access

Sylwia Tobólska, Sylwia Terpiłowska, Jerzy Jaroszewski and Andrzej Krzysztof Siwicki

Abstract

Introduction

Inosine pranobex (Methisoprinol, ISO, Isoprinosine) is an immuno-modulatory antiviral drug that has been licensed since 1971 in several countries worldwide. In humans, the drug is approved for the treatment of viral infections, and it might also have therapeutic use in animals. The aims of the presented work were to investigate the genotoxicity of inosine pranobex on BALB/3T3 clone A1 and HepG2 cell lines and to elucidate its mutagenicity using the Ames test.

Material and Methods

The BALB/3T3 clone A1 and HepG2 cells were incubated with inosine pranobex at concentrations from 0.1 to 1,000 μg/mL. The genotoxicity was determined by comet and micronucleus assays, and the mutagenicity was determined by Ames assay.

Results

Inosine pranobex did not induce a significant dose-related increase in the number of comets or micronuclei in BALB/3T3 clone A1 and HepG2 cells. Moreover, based on the results of the Ames test, it was concluded that inosine pranobex is not mutagenic in the Salmonella typhimurium reverse mutation assay.

Conclusion

Based on the results of a comet assay, micronucleus assay, and Ames test, it was concluded that inosine pranobex is neither genotoxic nor mutagenic.

Open access

Aleksandra Giżejewska, Agnieszka Nawrocka, Józef Szkoda, Jan Żmudzki, Jerzy Jaroszewski and Zygmunt Giżejewski

Abstract

Introduction: Hard antlers of deer are unique bioindicators of environmental metal pollutions, but sampling methods presented in the literature are inconsistent. Due to the specific growth pattern of antlers and their histological structure, sampling methods described in the literature were reviewed, the suitability of using mixed samples of both antler layers as element bioindicators was assessed, and the codified method of antler sampling used for bioindication was described. Material and Methods: Lead, cadmium, mercury, arsenic, copper, zinc, and iron in trabecular and cortical parts of hard antlers of red deer (Cervus elaphus) were determined using different methods of atomic absorption spectrometry (depending on the element). Results: Mean mercury content in trabecular bone (0.010 ±0.018 mg/kg) was 5 times higher than in cortical bone (0.002 ±0.003 mg/kg). Mean iron concentration was approximately 15 times higher in trabecular (239.83 ±130.15 mg/kg) than in cortical bone (16.17 ±16.44 mg/kg). Concentrations of other analysed elements did not differ statistically between antler layers. Conclusion: In mixed antler samples, concentrations of mercury and iron depend on the particular antler layer contents. This therefore warrants caution when comparing results across studies and specification of the sampling methodology of antlers is highly recommended.