Histopathological and biochemical Effects of 18β-glycyrrhetinic acid application on lipopolysaccharide-induced kidney toxicity in rats
Year 2024,
, 42 - 49, 30.04.2024
Elif Erbaş
,
Volkan Gelen
,
Seda Yakut
Abstract
Lipopolysaccharide (LPS) is an endotoxin found in the wall of gram-negative bacteria and causes acute inflammation when it enters the tissues. 18β-glycyrrhetinic acid (18β-GA) is a substance found in licorice root and is responsible for this plant's antiallergic, antioxidant, and anti-inflammatory activity. This study aimed to examine the possible effects of 18β-glycyrrhetinic acid on the damage caused by LPS in kidney tissue. The study divided 40 Sprague Dawley adult male rats into 5 equal groups (n = 8). The groups were created as follows; the control group; the group that received 1cc physiological saline throughout the experiment was the DMSO group; DMSO, an intraperitoneal carrier substance, was given. LPS group; A single dose of 7.5 mg/kg intraperitoneal (i.p) LPS was administered. 18β-GA50+LPS group; 18β-glycyrrhetinic acid was given by gavage at 50 mg/kg daily for 10 days, followed by a single dose of 7.5 mg/kg i.p. LPS was administered. 18β-GA100+LPS group; 18β-glycyrrhetinic acid was administered by gavage at 100 mg/kg daily for 10 days, followed by a single dose of 7.5 mg/kg i.p. LPS was administered. 18β-GA100 group; 18β-glycyrrhetinic was given by gavage at 100 mg/kg daily for 10 days. 24 hours after LPS application to all groups, the kidney tissues of the rats were removed under anesthesia and placed in 10% formaldehyde. Histopathological and oxidative stress parameters analyses were performed in kidney tissue.
References
- Abd El-Twab, S. M., Hozayen, W. G., Hussein, O. E., & Mahmoud, A. M. (2016). 18 β-Glycyrrhetinic acid protects against methotrexate-induced kidney injury by up-regulating the Nrf2/ARE/HO-1 pathway and endogenous antioxidants. Renal Failure, 38(9), 1516-1527. https://doi.org/10.1080/0886022X.2016.1216722
- Alwazeer, D. (2023). Recent knowledge of hydrogen therapy: Cases of rat. Rats, 1(1), 11–13. https://doi.org/10.5281/zenodo.8143351
- Ban, K. Y., Nam, G. Y., Kim, D., Oh, Y. S., & Jun, H. S. (2022). Prevention of LPS-induced acute kidney injury in mice by bavachin and its potential mechanisms. Antioxidants, 11(11), 2096. https://doi.org/10.3390/antiox11112096
- Boveris, A., & Cadenas, E. (1997). Cellular sources and steady-state levels of reactive oxygen species. Lung Biology in Health and Disease, 105, 1-26.
- Cunningham, P. N., Dyanov, H. M., Park, P., Wang, J., Newell, K. A., & Quigg, R. J. (2002). Acute renal failure in endotoxemia is caused by TNF acting directly on TNF receptor-1 in kidney. The Journal of Immunology, 168(11), 5817-5823. https://doi.org/10. 4049/jimmunol.168.11.5817
- Eisenbrand, G. (2006). Glycyrrhizin. Molecular Nutrition & Food Research, 50(11), 1087-1088.
- Gelen, V., Özkanlar, S., Kara, A., & Yeşildağ, A. (2023). Citrate‐coated silver nanoparticles loaded with agomelatine provide neuronal therapy in acute cerebral ischemia/reperfusion of rats by inhibiting the oxidative stress, endoplasmic reticulum stress, and P2X7 receptor‐mediated inflammasome. Environmental Toxicology. https://doi.org/10.1002/tox.24021
- Gelen, V., Sengul, E., Yildirim, S., & Cinar, İ. (2023). The role of GRP78/ATF6/IRE1 and caspase-3/Bax/Bcl2 signaling pathways in the protective effects of gallic acid against cadmium-induced liver damage in rats. Iranian Journal of Basic Medical Sciences, 26(11), 1326. https://doi.org/10.22038 %2FIJBMS .2023.71343.15525
- Gelen, V., Şengül, E., Yıldırım, S., Senturk, E., Tekin, S., & Kükürt, A. (2021). The protective effects of hesperidin and curcumin on 5-fluorouracil–induced nephrotoxicity in mice. Environmental Science and Pollution Research, 28, 47046-47055. https://doi.org/ 10.1007/s11356-021-13969-5
- Gomez, H., Ince, C., De Backer, D., Pickkers, P., Payen, D., Hotchkiss, J., & Kellum, J. A. (2014). A unified theory of sepsis-induced acute kidney injury: inflammation, microcirculatory dysfunction, bioenergetics and the tubular cell adaptation to injury. Shock (Augusta, Ga.), 41(1), 3. https://doi.org/10.1097%2FSHK.0000000000000052
- Gündoğdu, H., Uluman, E., Yıldız, S. E., Kılıçle, P. A., Gezer, A., & Sarı, E. K. (2023). Therapeutic effect of pomegranate peel extract on heme oxygen-free 1 (HO-1) and angiotensin-converting enzyme-2 (ACE-2) in the kidney tissue of mice treated with mitomycin. Rats, 1(2), 27-34. https://doi.org/ 10.5281/zenodo.10444360
- Hagiwara, S., Iwasaka, H., Maeda, H., & Noguchi, T. (2009). Landiolol, an ultrashort-acting β1-adrenoceptor antagonist, has protective effects in an LPS-induced systemic inflammation model. Shock, 31(5), 515-520. https://doi.org/10.1097/SHK. 0b013e3181863689
- Hasan, S. K., Khan, R., Ali, N., Khan, A. Q., Rehman, M. U., Tahir, M., ... & Sultana, S. (2015). 18-β Glycyrrhetinic acid alleviates 2-acetylaminofluorene-induced hepatotoxicity in Wistar rats: role in hyperproliferation, inflammation and oxidative stress. Human & Experimental Toxicology, 34(6), 628-641. https://doi.org/10.1177/0960327114554045
- Hayashi, H., Imanishi, N., Ohnishi, M., & Tojo, S. J. (2001). Sialyl Lewis X and anti-P-selectin antibody attenuate lipopolysaccharide-induced acute renal failure in rabbits. Nephron, 87(4), 352-360. https://doi.org/10.1159/000045942
- Iguchi S, Iwamura H, NishizakiM, Hayashi A, Senokuchi K, Kobayashi K, Sakaki K, Hachiya K, Ichioka Y, Kawamura M (1992). Development of a highly cardioselective ultra short-acting β-blocker, ONO-1101. Chemical and pharmaceutical bulletin, 40(6), 1462-1469. https://doi.org/10.1248/cpb. 40.1462
- Ishii, T., Itoh, K., Takahashi, S., Sato, H., Yanagawa, T., Katoh, Y., ... & Yamamoto, M. (2000). Transcription factor Nrf2 coordinately regulates a group of oxidative stress-inducible genes in macrophages. Journal of Biological Chemistry, 275(21), 16023-16029. https://doi.org/10.1074/jbc. 275.21.16023
- Itoh, K., Wakabayashi, N., Katoh, Y., Ishii, T., Igarashi, K., Engel, J. D., & Yamamoto, M. (1999). Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain. Genes & Development, 13(1), 76-86. https://doi.org/10.1101 /gad.13.1.76
- Kadkhodaee, M., & Qasemi, A. (2004). Inhibition of inducible nitric oxide synthase reduces lipopolysaccharide‐induced renal injury in the rat. Clinical and Experimental Pharmacology and Physiology, 31(12), 842-846. https://doi.org/ 10.1111/j.1440-1681.2004.04096.x
- Kalaiarasi, P., & Pugalendi, K. V. (2009). Antihyperglycemic effect of 18β-glycyrrhetinic acid, aglycone of glycyrrhizin, on streptozotocin-diabetic rats. European Journal of Pharmacology, 606(1-3), 269-273. https://doi.org/10.1016/j.ejphar.2008.12. 057
- Kang, L., Li, X. Q., Chen, C., & Wang, F. R. (2014). Research progress on structure modification and biological activity of 18β-glycyrrhetinic acid. Current Research in Complementary & Alternative Medicine, 1(1), e00008.
- Kao, T. C., Shyu, M. H., & Yen, G. C. (2010). Glycyrrhizic acid and 18β-glycyrrhetinic acid inhibit inflammation via PI3K/Akt/GSK3β signaling and glucocorticoid receptor activation. Journal of Agricultural and Food Chemistry, 58(15), 8623-8629. https://doi.org/10.1021/jf101841r
- Kara, A., Gedikli, S., Sengul, E., Gelen, V., & Ozkanlar, S. (2016). Oxidative stress and autophagy. Free Radicals and Diseases, 69-86. https://doi.org/10.5772/64569
- Kara, A., Gelen, V., & Kara, H. (2023). The Relationship of Some Neurodegenerative Diseases with Endoplasmic Reticulum Stress and Histopathological Changes in These Diseases: An Overview. Molecular Histopathology and Cytopathology. https://doi.org/ 10.5772/intechopen.111693
- Knotek, M., Rogachev, B., Wang, W., Ecder, T., Melnikov, V., Gengaro, P. E., ... & Schrier, R. W. (2001). Endotoxemic renal failure in mice: Role of tumor necrosis factor independent of inducible nitric oxide synthase. Kidney International, 59(6), 2243-2249. https://doi.org/10.1046/j.1523-1755.2001. 00740.x
- Kobayashi, S., Susa, T., Ishiguchi, H., Myoren, T., Murakami, W., Kato, T., ... & Yano, M. (2015). A low-dose β1-blocker in combination with milrinone improves intracellular Ca2+ handling in failing cardiomyocytes by inhibition of milrinone-induced diastolic Ca2+ leakage from the sarcoplasmic reticulum. PLoS One, 10(1), e0114314. https://doi.org/10.1371/journal.pone.0114314
- Lopes, J. A., Jorge, S., Resina, C., Santos, C., Pereira, Á., Neves, J., ... & Prata, M. M. (2009). Acute kidney injury in patients with sepsis: a contemporary analysis. International Journal of Infectious Diseases, 13(2), 176-181. https://doi.org/10.1016/j.ijid. 2008.05.1231
- Ma, T., Huang, C., Meng, X., Li, X., Zhang, Y., Ji, S., ... & Liang, H. (2016). A potential adjuvant chemotherapeutics, 18β-glycyrrhetinic acid, inhibits renal tubular epithelial cells apoptosis via enhancing BMP-7 epigenetically through targeting HDAC2. Scientific Reports, 6(1), 25396. https://doi.org/ 10.1038/srep25396
- Mahmoud, A. M., & Al Dera, H. S. (2015). 18β-Glycyrrhetinic acid exerts protective effects against cyclophosphamide-induced hepatotoxicity: potential role of PPARγ and Nrf2 upregulation. Genes & Nutrition, 10(6), 1-13. https://doi.org/10.1007/s12263-015-0491-1
- Morelli, A., Ertmer, C., Westphal, M., Rehberg, S., Kampmeier, T., Ligges, S., ... & Singer, M. (2013). Effect of heart rate control with esmolol on hemodynamic and clinical outcomes in patients with septic shock: a randomized clinical trial. Jama, 310(16), 1683-1691. https://doi.org/ 10.1001/jama.2013.278477
- Mori, K., Morisaki, H., Yajima, S., Suzuki, T., Ishikawa, A., Nakamura, N., ... & Takeda, J. (2011). Beta-1 blocker improves survival of septic rats through preservation of gut barrier function. Intensive Care Medicine, 37, 1849-1856. https://doi.org/10. 1007/s00134-011-2330-1
- Neveu, H. D. F. P. P., Kleinknecht, D., Brivet, F., Loirat, P. H., Landais, P., & French Study Group on Acute Renal Failure. (1996). Prognostic factors in acute renal failure due to sepsis. Results of a prospective multicentre study. Nephrology Dialysis Transplantation, 11(2), 293-299. https://doi.org/10. 1093/ndt/11.2.293
- Niu, X., Yao, Q., Li, W., Zang, L., Li, W., Zhao, J., ... & Zhi, W. (2019). Harmine mitigates LPS-induced acute kidney injury through inhibition of the TLR4-NF-κB/NLRP3 inflammasome signalling pathway in mice. European Journal of Pharmacology, 849, 160-169. https://doi.org/10.1016/j.ejphar.2019.01.062
- Ogura, Y., Jesmin, S., Yamaguchi, N., Oki, M., Shimojo, N., Islam, M. M., ... & Mizutani, T. (2014). Potential amelioration of upregulated renal HIF-1alpha–endothelin-1 system by landiolol hydrochloride in a rat model of endotoxemia. Life Sciences, 118(2), 347-356. https://doi.org/10. 1016/j.lfs.2014.05.007
- Ohkawa, H., Ohishi, N., & Yagi, K. (1979). Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical Biochemistry, 95(2), 351-358. https://doi.org/10.1016/0003-2697(79)90738-3
- Oppert, M., Engel, C., Brunkhorst, F. M., Bogatsch, H., Reinhart, K., Frei, U., ... & John, S. (2008). German Competence Network Sepsis (Sepnet) Acute renal failure in patients with severe sepsis and septic shock-a significant independent risk factor for mortality: results from the German prevalence study. Nephrology Dialysis Transplantation, 23(3), 904-909.
- Raghavan, V., & Weisz, O. A. (2015). Flow stimulated endocytosis in the proximal tubule. Current Opinion in Nephrology and Hypertension, 24(4), 359. https://doi.org/10.1097%2FMNH.0000000000000135
- Sedlak, J., & Lindsay, R. H. (1968). Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent. Analytical Biochemistry, 25, 192-205.
- Silvester, W., Bellomo, R., & Cole, L. (2001). Epidemiology, management, and outcome of severe acute renal failure of critical illness in Australia. Critical Care Medicine, 29(10), 1910-1915.
- Tiwari, M. M., Brock, R. W., Megyesi, J. K., Kaushal, G. P., & Mayeux, P. R. (2005). Disruption of renal peritubular blood flow in lipopolysaccharide-induced renal failure: role of nitric oxide and caspases. American Journal of Physiology-Renal Physiology, 289(6), F1324-F1332. https://doi.org/ 10.1152/ajprenal.00124.2005
- Tsao, C. M., Ho, S. T., Chen, A., Wang, J. J., Li, C. Y., Tsai, S. K., & Wu, C. C. (2004). Low-dose dexamethasone ameliorates circulatory failure and renal dysfunction in conscious rats with endotoxemia. Shock, 21(5), 484-491. https://doi.org/10.1097/01.shk. 0000124931.42937.23
- Uchino, S. (2005). Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) Investigators. Acute renal failure in critically ill patients: A multinational, multicenter study. JAMA, 294, 813-818.
- Wu, C. H., Chen, A. Z., & Yen, G. C. (2015). Protective effects of glycyrrhizic acid and 18β-glycyrrhetinic acid against cisplatin-induced nephrotoxicity in BALB/c mice. Journal of Agricultural and Food Chemistry, 63(4), 1200-1209. https://doi.org/10.1021/jf505471a
- Young DS. Effects of Drugs on Clinical Laboratory Tests. 4th ed. Washington, DC: AACC Press, 1995.
- Zeller, J. M., Buys, C. M., & Gudewicz, P. W. (1984). Effects of high-dose methotrexate on rat alveolar and inflammatory macrophage populations. Inflammation, 8, 231-239.
Year 2024,
, 42 - 49, 30.04.2024
Elif Erbaş
,
Volkan Gelen
,
Seda Yakut
References
- Abd El-Twab, S. M., Hozayen, W. G., Hussein, O. E., & Mahmoud, A. M. (2016). 18 β-Glycyrrhetinic acid protects against methotrexate-induced kidney injury by up-regulating the Nrf2/ARE/HO-1 pathway and endogenous antioxidants. Renal Failure, 38(9), 1516-1527. https://doi.org/10.1080/0886022X.2016.1216722
- Alwazeer, D. (2023). Recent knowledge of hydrogen therapy: Cases of rat. Rats, 1(1), 11–13. https://doi.org/10.5281/zenodo.8143351
- Ban, K. Y., Nam, G. Y., Kim, D., Oh, Y. S., & Jun, H. S. (2022). Prevention of LPS-induced acute kidney injury in mice by bavachin and its potential mechanisms. Antioxidants, 11(11), 2096. https://doi.org/10.3390/antiox11112096
- Boveris, A., & Cadenas, E. (1997). Cellular sources and steady-state levels of reactive oxygen species. Lung Biology in Health and Disease, 105, 1-26.
- Cunningham, P. N., Dyanov, H. M., Park, P., Wang, J., Newell, K. A., & Quigg, R. J. (2002). Acute renal failure in endotoxemia is caused by TNF acting directly on TNF receptor-1 in kidney. The Journal of Immunology, 168(11), 5817-5823. https://doi.org/10. 4049/jimmunol.168.11.5817
- Eisenbrand, G. (2006). Glycyrrhizin. Molecular Nutrition & Food Research, 50(11), 1087-1088.
- Gelen, V., Özkanlar, S., Kara, A., & Yeşildağ, A. (2023). Citrate‐coated silver nanoparticles loaded with agomelatine provide neuronal therapy in acute cerebral ischemia/reperfusion of rats by inhibiting the oxidative stress, endoplasmic reticulum stress, and P2X7 receptor‐mediated inflammasome. Environmental Toxicology. https://doi.org/10.1002/tox.24021
- Gelen, V., Sengul, E., Yildirim, S., & Cinar, İ. (2023). The role of GRP78/ATF6/IRE1 and caspase-3/Bax/Bcl2 signaling pathways in the protective effects of gallic acid against cadmium-induced liver damage in rats. Iranian Journal of Basic Medical Sciences, 26(11), 1326. https://doi.org/10.22038 %2FIJBMS .2023.71343.15525
- Gelen, V., Şengül, E., Yıldırım, S., Senturk, E., Tekin, S., & Kükürt, A. (2021). The protective effects of hesperidin and curcumin on 5-fluorouracil–induced nephrotoxicity in mice. Environmental Science and Pollution Research, 28, 47046-47055. https://doi.org/ 10.1007/s11356-021-13969-5
- Gomez, H., Ince, C., De Backer, D., Pickkers, P., Payen, D., Hotchkiss, J., & Kellum, J. A. (2014). A unified theory of sepsis-induced acute kidney injury: inflammation, microcirculatory dysfunction, bioenergetics and the tubular cell adaptation to injury. Shock (Augusta, Ga.), 41(1), 3. https://doi.org/10.1097%2FSHK.0000000000000052
- Gündoğdu, H., Uluman, E., Yıldız, S. E., Kılıçle, P. A., Gezer, A., & Sarı, E. K. (2023). Therapeutic effect of pomegranate peel extract on heme oxygen-free 1 (HO-1) and angiotensin-converting enzyme-2 (ACE-2) in the kidney tissue of mice treated with mitomycin. Rats, 1(2), 27-34. https://doi.org/ 10.5281/zenodo.10444360
- Hagiwara, S., Iwasaka, H., Maeda, H., & Noguchi, T. (2009). Landiolol, an ultrashort-acting β1-adrenoceptor antagonist, has protective effects in an LPS-induced systemic inflammation model. Shock, 31(5), 515-520. https://doi.org/10.1097/SHK. 0b013e3181863689
- Hasan, S. K., Khan, R., Ali, N., Khan, A. Q., Rehman, M. U., Tahir, M., ... & Sultana, S. (2015). 18-β Glycyrrhetinic acid alleviates 2-acetylaminofluorene-induced hepatotoxicity in Wistar rats: role in hyperproliferation, inflammation and oxidative stress. Human & Experimental Toxicology, 34(6), 628-641. https://doi.org/10.1177/0960327114554045
- Hayashi, H., Imanishi, N., Ohnishi, M., & Tojo, S. J. (2001). Sialyl Lewis X and anti-P-selectin antibody attenuate lipopolysaccharide-induced acute renal failure in rabbits. Nephron, 87(4), 352-360. https://doi.org/10.1159/000045942
- Iguchi S, Iwamura H, NishizakiM, Hayashi A, Senokuchi K, Kobayashi K, Sakaki K, Hachiya K, Ichioka Y, Kawamura M (1992). Development of a highly cardioselective ultra short-acting β-blocker, ONO-1101. Chemical and pharmaceutical bulletin, 40(6), 1462-1469. https://doi.org/10.1248/cpb. 40.1462
- Ishii, T., Itoh, K., Takahashi, S., Sato, H., Yanagawa, T., Katoh, Y., ... & Yamamoto, M. (2000). Transcription factor Nrf2 coordinately regulates a group of oxidative stress-inducible genes in macrophages. Journal of Biological Chemistry, 275(21), 16023-16029. https://doi.org/10.1074/jbc. 275.21.16023
- Itoh, K., Wakabayashi, N., Katoh, Y., Ishii, T., Igarashi, K., Engel, J. D., & Yamamoto, M. (1999). Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain. Genes & Development, 13(1), 76-86. https://doi.org/10.1101 /gad.13.1.76
- Kadkhodaee, M., & Qasemi, A. (2004). Inhibition of inducible nitric oxide synthase reduces lipopolysaccharide‐induced renal injury in the rat. Clinical and Experimental Pharmacology and Physiology, 31(12), 842-846. https://doi.org/ 10.1111/j.1440-1681.2004.04096.x
- Kalaiarasi, P., & Pugalendi, K. V. (2009). Antihyperglycemic effect of 18β-glycyrrhetinic acid, aglycone of glycyrrhizin, on streptozotocin-diabetic rats. European Journal of Pharmacology, 606(1-3), 269-273. https://doi.org/10.1016/j.ejphar.2008.12. 057
- Kang, L., Li, X. Q., Chen, C., & Wang, F. R. (2014). Research progress on structure modification and biological activity of 18β-glycyrrhetinic acid. Current Research in Complementary & Alternative Medicine, 1(1), e00008.
- Kao, T. C., Shyu, M. H., & Yen, G. C. (2010). Glycyrrhizic acid and 18β-glycyrrhetinic acid inhibit inflammation via PI3K/Akt/GSK3β signaling and glucocorticoid receptor activation. Journal of Agricultural and Food Chemistry, 58(15), 8623-8629. https://doi.org/10.1021/jf101841r
- Kara, A., Gedikli, S., Sengul, E., Gelen, V., & Ozkanlar, S. (2016). Oxidative stress and autophagy. Free Radicals and Diseases, 69-86. https://doi.org/10.5772/64569
- Kara, A., Gelen, V., & Kara, H. (2023). The Relationship of Some Neurodegenerative Diseases with Endoplasmic Reticulum Stress and Histopathological Changes in These Diseases: An Overview. Molecular Histopathology and Cytopathology. https://doi.org/ 10.5772/intechopen.111693
- Knotek, M., Rogachev, B., Wang, W., Ecder, T., Melnikov, V., Gengaro, P. E., ... & Schrier, R. W. (2001). Endotoxemic renal failure in mice: Role of tumor necrosis factor independent of inducible nitric oxide synthase. Kidney International, 59(6), 2243-2249. https://doi.org/10.1046/j.1523-1755.2001. 00740.x
- Kobayashi, S., Susa, T., Ishiguchi, H., Myoren, T., Murakami, W., Kato, T., ... & Yano, M. (2015). A low-dose β1-blocker in combination with milrinone improves intracellular Ca2+ handling in failing cardiomyocytes by inhibition of milrinone-induced diastolic Ca2+ leakage from the sarcoplasmic reticulum. PLoS One, 10(1), e0114314. https://doi.org/10.1371/journal.pone.0114314
- Lopes, J. A., Jorge, S., Resina, C., Santos, C., Pereira, Á., Neves, J., ... & Prata, M. M. (2009). Acute kidney injury in patients with sepsis: a contemporary analysis. International Journal of Infectious Diseases, 13(2), 176-181. https://doi.org/10.1016/j.ijid. 2008.05.1231
- Ma, T., Huang, C., Meng, X., Li, X., Zhang, Y., Ji, S., ... & Liang, H. (2016). A potential adjuvant chemotherapeutics, 18β-glycyrrhetinic acid, inhibits renal tubular epithelial cells apoptosis via enhancing BMP-7 epigenetically through targeting HDAC2. Scientific Reports, 6(1), 25396. https://doi.org/ 10.1038/srep25396
- Mahmoud, A. M., & Al Dera, H. S. (2015). 18β-Glycyrrhetinic acid exerts protective effects against cyclophosphamide-induced hepatotoxicity: potential role of PPARγ and Nrf2 upregulation. Genes & Nutrition, 10(6), 1-13. https://doi.org/10.1007/s12263-015-0491-1
- Morelli, A., Ertmer, C., Westphal, M., Rehberg, S., Kampmeier, T., Ligges, S., ... & Singer, M. (2013). Effect of heart rate control with esmolol on hemodynamic and clinical outcomes in patients with septic shock: a randomized clinical trial. Jama, 310(16), 1683-1691. https://doi.org/ 10.1001/jama.2013.278477
- Mori, K., Morisaki, H., Yajima, S., Suzuki, T., Ishikawa, A., Nakamura, N., ... & Takeda, J. (2011). Beta-1 blocker improves survival of septic rats through preservation of gut barrier function. Intensive Care Medicine, 37, 1849-1856. https://doi.org/10. 1007/s00134-011-2330-1
- Neveu, H. D. F. P. P., Kleinknecht, D., Brivet, F., Loirat, P. H., Landais, P., & French Study Group on Acute Renal Failure. (1996). Prognostic factors in acute renal failure due to sepsis. Results of a prospective multicentre study. Nephrology Dialysis Transplantation, 11(2), 293-299. https://doi.org/10. 1093/ndt/11.2.293
- Niu, X., Yao, Q., Li, W., Zang, L., Li, W., Zhao, J., ... & Zhi, W. (2019). Harmine mitigates LPS-induced acute kidney injury through inhibition of the TLR4-NF-κB/NLRP3 inflammasome signalling pathway in mice. European Journal of Pharmacology, 849, 160-169. https://doi.org/10.1016/j.ejphar.2019.01.062
- Ogura, Y., Jesmin, S., Yamaguchi, N., Oki, M., Shimojo, N., Islam, M. M., ... & Mizutani, T. (2014). Potential amelioration of upregulated renal HIF-1alpha–endothelin-1 system by landiolol hydrochloride in a rat model of endotoxemia. Life Sciences, 118(2), 347-356. https://doi.org/10. 1016/j.lfs.2014.05.007
- Ohkawa, H., Ohishi, N., & Yagi, K. (1979). Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Analytical Biochemistry, 95(2), 351-358. https://doi.org/10.1016/0003-2697(79)90738-3
- Oppert, M., Engel, C., Brunkhorst, F. M., Bogatsch, H., Reinhart, K., Frei, U., ... & John, S. (2008). German Competence Network Sepsis (Sepnet) Acute renal failure in patients with severe sepsis and septic shock-a significant independent risk factor for mortality: results from the German prevalence study. Nephrology Dialysis Transplantation, 23(3), 904-909.
- Raghavan, V., & Weisz, O. A. (2015). Flow stimulated endocytosis in the proximal tubule. Current Opinion in Nephrology and Hypertension, 24(4), 359. https://doi.org/10.1097%2FMNH.0000000000000135
- Sedlak, J., & Lindsay, R. H. (1968). Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent. Analytical Biochemistry, 25, 192-205.
- Silvester, W., Bellomo, R., & Cole, L. (2001). Epidemiology, management, and outcome of severe acute renal failure of critical illness in Australia. Critical Care Medicine, 29(10), 1910-1915.
- Tiwari, M. M., Brock, R. W., Megyesi, J. K., Kaushal, G. P., & Mayeux, P. R. (2005). Disruption of renal peritubular blood flow in lipopolysaccharide-induced renal failure: role of nitric oxide and caspases. American Journal of Physiology-Renal Physiology, 289(6), F1324-F1332. https://doi.org/ 10.1152/ajprenal.00124.2005
- Tsao, C. M., Ho, S. T., Chen, A., Wang, J. J., Li, C. Y., Tsai, S. K., & Wu, C. C. (2004). Low-dose dexamethasone ameliorates circulatory failure and renal dysfunction in conscious rats with endotoxemia. Shock, 21(5), 484-491. https://doi.org/10.1097/01.shk. 0000124931.42937.23
- Uchino, S. (2005). Beginning and Ending Supportive Therapy for the Kidney (BEST Kidney) Investigators. Acute renal failure in critically ill patients: A multinational, multicenter study. JAMA, 294, 813-818.
- Wu, C. H., Chen, A. Z., & Yen, G. C. (2015). Protective effects of glycyrrhizic acid and 18β-glycyrrhetinic acid against cisplatin-induced nephrotoxicity in BALB/c mice. Journal of Agricultural and Food Chemistry, 63(4), 1200-1209. https://doi.org/10.1021/jf505471a
- Young DS. Effects of Drugs on Clinical Laboratory Tests. 4th ed. Washington, DC: AACC Press, 1995.
- Zeller, J. M., Buys, C. M., & Gudewicz, P. W. (1984). Effects of high-dose methotrexate on rat alveolar and inflammatory macrophage populations. Inflammation, 8, 231-239.