Hepatoprotective and anti-inflammatory effects of entecavir or probiotics on Oxaliplatin-Induced Liver Injury in the rats

Authors

DOI:

https://doi.org/10.25156/ptj.v12n2y2022.pp174-179

Keywords:

oxaliplatin, entecavir, probiotic, liver function tests, inflammatory cytokines

Abstract

Oxaliplatin (OXA), a current cancer chemotherapeutic, has low efficacy and is linked to serious adverse effects, including liver damage. We anticipated that probiotics and entecavir would help reduce OXA-induced liver damage because the pathophysiology of drug-induced liver damage is thought to be related to the disordered gut microbiota. Twenty-four rats were used in this study and divided into 4 groups: control group (n=6), OXA group (n=6), entecavir (ENT) group (n=6), and probiotics (PRO) group (n=6). After 3 weeks, all rats were sacrificed, and blood samples were analyzed for alkaline phosphatase (ALP), alanine aminotransferase (ALT) and aspartate aminotransferase (AST), interleukin 6 (IL-6), and IL-1. Serum measurement of biochemical parameters showed a significant increase in ALP in the OXA group compared to the control group (p<0.0001). The treatment with ENT or PRO along with OXA alleviated these changes. Significant elevation of serum ALT (p=0.041) and non-significant (p=0.210) increase of AST was observed in OXA-treated rats as compared with control rats. The administration of ENT or PRO along OXA restored these changes, but they did not reach the levels of control rats. Significant elevations of serum IL-1 (p=0.024) and a non-significant (p=0.114) increase of IL-6 were observed in OXA-treated rats compared to control rats. The administration of ENT or PRO along OXA reduced inflammatory cytokines' levels but they did not return to the baseline. The treatment with ENT or PRO was beneficial in reducing the severity of OXA-induced liver injury, likely by reducing inflammatory responses and liver function tests.

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References

AZAD, M., KALAM, A., SARKER, M., LI, T. & YIN, J. 2018. Probiotic species in the modulation of gut microbiota: an overview. BioMed research international, 2018.

BADARY, O. A., ABDEL-MAKSOUD, S., AHMED, W. A. & OWIEDA, G. H. 2005. Naringenin attenuates cisplatin nephrotoxicity in rats. Life sciences, 76, 2125-2135.

BAI, X., CHEN, Y., HOU, X., HUANG, M. & JIN, J. 2016. Emerging role of NRF2 in chemoresistance by regulating drug-metabolizing enzymes and efflux transporters. Drug metabolism reviews, 48, 541-567.

CHUN, Y. S., LAURENT, A., MARU, D. & VAUTHEY, J.-N. 2009. Management of chemotherapy-associated hepatotoxicity in colorectal liver metastases. The lancet oncology, 10, 278-286.

CORREIA, S., CARVALHO, C., CARDOSO, S., SANTOS, R., SANTOS, M., OLIVEIRA, C., PERRY, G., ZHU, X., SMITH, M. & MOREIRA, P. 2010. Mitochondrial preconditioning: a potential neuroprotective strategy. Frontiers in Aging Neuroscience, 2.

FENG, J., GAO, M., ZHAO, C., YANG, J., GAO, H., LU, X., JU, R., ZHANG, X. & ZHANG, Y. 2022. Oral Administration of Probiotics Reduces Chemotherapy-Induced Diarrhea and Oral Mucositis: A Systematic Review and Meta-Analysis. Frontiers in nutrition, 9.

FENG, P., YE, Z., HAN, H., LING, Z., ZHOU, T., ZHAO, S., VIRK, A. K., KAKADE, A., ABOMOHRA, A. E.-F. & EL-DALATONY, M. M. 2020. Tibet plateau probiotic mitigates chromate toxicity in mice by alleviating oxidative stress in gut microbiota. Communications biology, 3, 1-12.

FLOREA, A.-M. & BÜSSELBERG, D. 2011. Cisplatin as an Anti-Tumor Drug: Cellular Mechanisms of Activity, Drug Resistance and Induced Side Effects. Cancers, 3, 1351-1371.

FORSGÅRD, R. A., MARRACHELLI, V. G., KORPELA, K., FRIAS, R., COLLADO, M. C., KORPELA, R., MONLEON, D., SPILLMANN, T. & ÖSTERLUND, P. 2017. Chemotherapy-induced gastrointestinal toxicity is associated with changes in serum and urine metabolome and fecal microbiota in male Sprague–Dawley rats. Cancer chemotherapy and pharmacology, 80, 317-332.

HONG, M., KIM, S. W., HAN, S. H., KIM, D. J., SUK, K. T., KIM, Y. S., KIM, M. J., KIM, M. Y., BAIK, S. K. & HAM, Y. L. 2015.

Probiotics (Lactobacillus rhamnosus R0011 and acidophilus R0052) reduce the expression of toll-like receptor 4 in mice with alcoholic liver disease. PLoS One, 10, e0117451.

HUBERT, J., THIBOUTOT, E., DUBÉ, P., CLOUTIER, A. S., DROLET, P. & SIDERIS, L. 2015. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy with oxaliplatin for peritoneal mesothelioma: preliminary results and survival analysis. Surg Oncol, 24, 41-6.

INOKUCHI, S., TSUKAMOTO, H., PARK, E., LIU, Z. X., BRENNER, D. A. & SEKI, E. 2011. Toll‐like receptor 4 mediates alcohol‐induced steatohepatitis through bone marrow‐derived and endogenous liver cells in mice. Alcoholism: Clinical and Experimental Research, 35, 1509-1518.

KONECNY, F. 2021. Rodent General Anesthesia Suitable for Measurement of Experimental Invasive Hemodynamics. European Journal of Biology and Biotechnology, 2, 33-43.

LI, F. Y., HAO, H. P., HAO, K., YAN, T. T. & WANG, G. J. 2013. Effect of diammonium glycyrrhizinate on entecavir pharmacokinetics in rats. Chin J Nat Med, 11, 309-13.

LU, Y.-X., HE, C.-Z., WANG, Y.-X., AI, Z.-S., LIANG, P. & YANG, C.-Q. 2021. Effect of Entecavir on the Intestinal Microflora in Patients with Chronic Hepatitis B: A Controlled Cross-Sectional and Longitudinal Real-World Study. Infectious Diseases and Therapy, 10, 241-252.

LUO, H., LIU, L., ZHAO, J., MI, X., WANG, Q. & YU, M. 2020. Effects of oxaliplatin on inflammation and intestinal floras in rats with colorectal cancer. European Review for Medical and Pharmacological Sciences, 24, 10542-10549.

NCBI. 2018. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): Nationa Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Entecavir. [Online]. Available: https://www.ncbi.nlm.nih.gov/books/NBK548075/ [Accessed].

ROBINSON, S., MANN, J., VASILAKI, A., MATHERS, J., BURT, A., OAKLEY, F., WHITE, S. & MANN, D. 2013. Pathogenesis of FOLFOX induced sinusoidal obstruction syndrome in a murine chemotherapy model. Journal of hepatology, 59, 318-326.

SKRYPNIK, K., BOGDAŃSKI, P., SCHMIDT, M. & SULIBURSKA, J. 2019. The Effect of Multispecies Probiotic Supplementation on Iron Status in Rats. Biol Trace Elem Res, 192, 234-243.

STOJANOVSKA, V., MCQUADE, R. M., FRASER, S., PRAKASH, M., GONDALIA, S., STAVELY, R., PALOMBO, E., APOSTOLOPOULOS, V., SAKKAL, S. & NURGALI, K. 2018. Oxaliplatin-induced changes in microbiota, TLR4+ cells and enhanced HMGB1 expression in the murine colon. PloS one, 13, e0198359.

WANG, H.-W., LAI, H.-C., HU, T.-H., SU, W.-P., LU, S.-N., LIN, C.-H., HUNG, C.-H., CHUANG, P.-H., WANG, J.-H. & LEE, M.-H. 2020. On-treatment changes in FIB-4 and 1-year FIB-4 values help identify patients with chronic hepatitis B receiving entecavir therapy who have the lowest risk of hepatocellular carcinoma. Cancers, 12, 1177.

WANG, Y., ZHANG, Y., LIU, Y., XU, J. & LIU, Y. 2021. Gut–Liver Axis: Liver Sinusoidal Endothelial Cells Function as the Hepati Barrier in Colitis-Induced Liver Injury. Frontiers in Cell and Developmental Biology, 1895.

WASEEM, M., BHARDWAJ, M., TABASSUM, H., RAISUDDIN, S. & PARVEZ, S. 2015. Cisplatin hepatotoxicity mediated by mitochondrial stress. Drug Chem Toxicol, 38, 452-9.

WOODHOUSE, C., PATEL, V., SINGANAYAGAM, A. & SHAWCROSS, D. 2018. the gut microbiome as a therapeutic target in the pathogenesis and treatment of chronic liver disease. Alimentary pharmacology & therapeutics, 47, 192-202.

YOO, S. H., JANG, J. W., KWON, J. H., JUNG, S. M., JANG, B. & CHOI, J. Y. 2016. Preemptive antiviral therapy with entecavir can reduce acute deterioration of hepatic function following transarterial chemoembolization. Clinical and molecular hepatology, 22, 458.

ZHANG, X.-Y., DUAN, C.-T., ZHAO, N., XIAO, H., SHI, M.-W., ZHANG, X.-L. & XU, J. 2010. Facile fabrication of large scale microtubes with a natural template — Kapok fiber. Chinese Journal of Polymer Science, 28, 841-847.

ZICCA, A., CAFAGGI, S., MARIGGIÒ, M. A., VANNOZZI, M. O., OTTONE, M., BOCCHINI, V., CAVIGLIOLI, G. & VIALE, M. 2002. Reduction of cisplatin hepatotoxicity by procainamide hydrochloride in rats. Eur J Pharmacol, 442, 265-72.

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Published

2023-04-16

How to Cite

Askandar, A. A., & Alhassani, A. N. (2023). Hepatoprotective and anti-inflammatory effects of entecavir or probiotics on Oxaliplatin-Induced Liver Injury in the rats. Polytechnic Journal, 12(2), 174-179. https://doi.org/10.25156/ptj.v12n2y2022.pp174-179

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Research Articles