Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Loganin Ameliorates Acute Kidney Injury and Restores Tofacitinib Metabolism in Rats: Implications for Renal Protection and Drug Interaction

  • Hyeon Gyeom Choi (College of Pharmacy and Research Institute of Pharmaceutical Science and Technology, Ajou University) ;
  • So Yeon Park (Department of Biohealth Regulatory Science, Graduate School of Ajou University) ;
  • Sung Hun Bae (AI-Superconvergence KIURI Translational Research Center, Ajou University School of Medicine) ;
  • Sun-Young Chang (College of Pharmacy and Research Institute of Pharmaceutical Science and Technology, Ajou University) ;
  • So Hee Kim (College of Pharmacy and Research Institute of Pharmaceutical Science and Technology, Ajou University)
  • Received : 2024.01.10
  • Accepted : 2024.03.19
  • Published : 2024.09.01
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Abstract

Tofacitinib, a Janus kinase (JAK) inhibitor used to treat rheumatoid arthritis, is metabolized through hepatic cytochrome P450 (CYP), specifically CYP3A1/2 and CYP2C11. Prolonged administration of rheumatoid arthritis medications is generally associated with an increased risk of renal toxicity. Loganin (LGN), an iridoid glycoside, has hepatorenal regenerative properties. This study investigates the potential of LGN to mitigate acute kidney injury (AKI) and its effects on the pharmacokinetics of tofacitinib in rats with cisplatin-induced AKI. Both intravenous and oral administration of tofacitinib to AKI rats significantly increased the area under the plasma concentration-time curve from time 0 to infinity (AUC) compared with control (CON) rats, an increase attributed to the decelerated non-renal clearance (CLNR) and renal clearance (CLR) of tofacitinib. Administration of LGN to AKI rats, however, protected kidneys from severe impairment, restoring the pharmacokinetic parameters (AUC, CLNR, and CLR) of tofacitinib to those observed in untreated CON rats, with partial recovery of kidney function, as evidenced by an increase in creatinine clearance. Possible interactions between drugs and natural components should be considered, especially when co-administering both a drug and a natural extract containing LGN or iridoid glycosides to patients with kidney injury.

Keywords

Acknowledgement

This work was partly supported by the Basic Science Research Program through a grant from the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (MSIT) (NRF-2021R1A2C1011142) and by the GRRC program of Gyeonggi province (GRRCAjou2023-B04), Korea.

References

  1. Abd El-Kader, M. and Taha, R. I. (2020) Comparative nephroprotective effects of curcumin and etoricoxib against cisplatin-induced acute kidney injury in rats. Acta Histochem. 122, 151534.
  2. Arjumand, W., Seth, A. and Sultana, S. (2011) Rutin attenuates cisplatin induced renal inflammation and apoptosis by reducing NFκB, TNF-α and caspase-3 expression in wistar rats. Food Chem. Toxicol. 49, 2013-2021.
  3. Bae, S. H., Chang, S. Y. and Kim, S. H. (2020) Slower elimination of tofacitinib in acute renal failure rat models: contribution of hepatic metabolism and renal excretion. Pharmaceutics 12, 714.
  4. Bae, S. H., Choi, H. G., Park, S. Y., Chang, S. Y., Kim, H. and Kim, S. H. (2022) Effects of isosakuranetin on pharmacokinetic changes of tofacitinib in rats with N-dimethylnitrosamine-induced liver cirrhosis. Pharmaceutics 14, 2684.
  5. Banerjee, S., Das, R. K., Giffear, K. A. and Shapiro, B. H. (2015) Permanent uncoupling of male-specific CYP2C11 transcription/translation by perinatal glutamate. Toxicol. Appl. Pharmacol. 284, 79-91.
  6. Bannwarth, B., Kostine, M. and Poursac, N. (2013) A pharmacokinetic and clinical assessment of tofacitinib for the treatment of rheumatoid arthritis. Expert Opin. Drug Metab. Toxicol. 9, 753-761.
  7. Barre, J., Chamouard, J. M., Houin, G. and Tillement, J. P. (1985) Equilibrium dialysis, ultrafiltration, and ultracentrifugation compared for determining the plasma-protein-binding characteristics of valproic acid. Clin. Chem. 31, 60-64.
  8. Chiou, W. L. (1978) Critical evaluation of the potential error in pharmacokinetic studies of using the linear trapezoidal rule method for the calculation of the area under the plasma level--time curve. J. Pharmacokinet. Biopharm. 6, 539-546.
  9. Claxton, L., Taylor, M., Soonasra, A., Bourret, J. A. and Gerber, R. A. (2018) An economic evaluation of tofacitinib treatment in rheumatoid arthritis after methotrexate or after 1 or 2 TNF inhibitors from a U.S. payer perspective. J. Manag. Care Spec. Pharm. 24, 1010-1017.
  10. Cui, Y., Wang, Y., Zhao, D., Feng, X., Zhang, L. and Liu, C. (2018) Loganin prevents BV-2 microglia cells from Aβ1-42 -induced inflammation via regulating TLR4/TRAF6/NF-κB axis. Cell Biol. Int. 42, 1632-1642.
  11. Dachuri, V., Song, P. H., Ku, S. K. and Song, C. H. (2020) Protective effects of traditional herbal formulas on cisplatin-induced nephrotoxicity in renal epithelial cells via antioxidant and antiapoptotic properties. Evid. Based Complement. Alternat. Med. 2020, 5807484.
  12. Dong, Y., Feng, Z. L., Chen, H. B., Wang, F. S., and Lu, J. H. (2018) Corni Fructus: a review of chemical constituents and pharmacological activities. Chin. Med. 13, 34.
  13. Dowling, T. C., Briglia, A. E., Fink, J. C., Hanes, D. S., Light, P. D., Stackiewicz, L., Karyekar, C. S., Eddington, N. D., Weir, M. R. and Henrich, W. L. (2003) Characterization of hepatic cytochrome p4503A activity in patients with end-stage renal disease. Clin. Pharmacol. Ther. 73, 427-434.
  14. Dowty, M. E., Lin, J., Ryder, T. F., Wang, W., Walker, G. S., Vaz, A., Chan, G. L., Krishnaswami, S. and Prakash, C. (2014) The pharmacokinetics, metabolism, and clearance mechanisms of tofacitinib, a janus kinase inhibitor, in humans. Drug Metab. Dispos. 42, 759-773.
  15. Duggleby, R. G. (1995) Analysis of enzyme progress curves by nonlinear regression. Methods Enzymol. 249, 61-90.
  16. Feng, Y., Liu, Y., Wang, L., Cai, X., Wang, D., Wu, K., Chen, H., Li, J. and Lei, W. (2013) Sustained oxidative stress causes late acute renal failure via duplex regulation on p38 MAPK and Akt phosphorylation in severely burned rats. PLoS One 8, e54593.
  17. Fukuda, T., Naganuma, M. and Kanai, T. (2019) Current new challenges in the management of ulcerative colitis. Intest. Res. 17, 36-44.
  18. Gibaldi, M. and Perrier, D. (1982) Pharmacokinetics, 2nd ed. Marcel-Dekker, New York.
  19. Jiang, W. L., Zhang, S. P., Hou, J. and Zhu, H. B. (2012) Effect of loganin on experimental diabetic nephropathy. Phytomedicine 19, 217-222.
  20. Kim, M. J., Bae, G. S., Jo, I. J., Choi, S. B., Kim, D. G., Shin, J. Y., Lee, S. K., Kim, M. J., Shin, S., Song, H. J. and Park, S. J. (2015) Loganin protects against pancreatitis by inhibiting NF-κB activation. Eur. J. Pharmacol. 765, 541-550.
  21. Kim, D. U., Kim, D. G., Choi, J. W., Shin, J. Y., Kweon, B., Zhou, Z., Lee, H. S., Song, H. J., Bae, G. S. and Park, S. J. (2021) Loganin attenuates the severity of acute kidney injury induced by cisplatin through the inhibition of ERK activation in mice. Int. J. Mol. Sci. 22, 1421.
  22. Kim, J. E., Park, M. Y. and Kim, S. H. (2020) Simple determination and quantification of tofacitinib, a JAK inhibitor, in rat plasma, urine and tissue homogenates by HPLC and its application to a pharmacokinetic study. J. Pharm. Investig. 50, 603-612.
  23. Koivuniemi, R., Paimela, L., Suomalainen, R. and Leirisalo-Repo, M. (2008) Amyloidosis as a cause of death in patients with rheumatoid arthritis. Clin. Exp. Rheumatol. 26, 408-413.
  24. Krishnaswami, S., Chow, V., Boy, M., Wang, C. and Chan, G. (2014) Pharmacokinetics of tofacitinib, a janus kinase inhibitor, in patients with impaired renal function and end-stage renal disease. J. Clin. Pharmacol. 54, 46-52.
  25. Kwon, S. H., Kim, J. A., Hong, S. I., Jung, Y. H., Kim, H. C., Lee, S. Y. and Jang, C. G. (2011) Loganin protects against hydrogen peroxide-induced apoptosis by inhibiting phosphorylation of JNK, p38, and ERK 1/2 MAPKs in SH-SY5Y cells. Neurochem. Int. 58, 533-541.
  26. Lee, Y. K., Chin, Y. W. and Choi, Y. H. (2013) Effects of Korean red ginseng extract on acute renal failure induced by gentamicin and pharmacokinetic changes by metformin in rats. Food Chem. Toxicol. 59, 153-159.
  27. Lee, J. S. and Kim, S. H. (2019) Dose-dependent pharmacokinetics of tofacitinib in rats: influence of hepatic and intestinal first-pass metabolism. Pharmaceutics 11, 318.
  28. Lee, J. S., Oh, J. S., Kim, Y. G., Lee, C. K., Yoo, B. and Hong, S. (2020) Methotrexate-related toxicity in patients with rheumatoid arthritis and renal dysfunction. Rheumatol. Int. 40, 765-770.
  29. Lee, K. Y., Sung, S. H., Kim, S. H., Jang, Y. P., Oh, T. H. and Kim, Y. C. (2009) Cognitive-enhancing activity of loganin isolated from Cornus officinalis in scopolamine-induced amnesic mice. Arch. Pharm. Res. 32, 677-683.
  30. Lee, S. Y., Yean, M. H., Kim, J. S., Lee, J. H. and Kang, S. S. (2011) Phytochemical studies on Rehmanniae Radix. Kor. J. Pharmacogn. 42, 127-137.
  31. Lewis, D. F. V. (1996) P450 substrate specificity and metabolism. Cytochromes 450. In Structure, Function and Mechanism, pp. 102-116. Taylor & Francis Inc., Philadelphia.
  32. Malik, S., Suchal, K., Bhatia, J., Gamad, N., Dinda, A. K., Gupta, Y. K. and Arya, D. S. (2016) Molecular mechanisms underlying attenuation of cisplatin-induced acute kidney injury by epicatechingallate. Lab. Invest. 96, 853-861.
  33. Martinez-Salgado, C., Lopez-Hernandez, F. J. and Lopez-Novoa, J. M. (2007) Glomerular nephrotoxicity of aminoglycosides. Toxicol. Appl. Pharmacol. 223, 86-98.
  34. Mitruka, B. M. and Rawnsley, H. M. (1981) Clinical Biochemical and Hematological Reference Values in Normal Experimental Animals and Normal Humans, 2nd ed. Masson Publishing USA Inc., New York.
  35. Moller, B., Pruijm, M., Adler, S., Scherer, A., Villiger, P. M. and Finckh, A.; Swiss Clinical Quality Management in Rheumatic Diseases (SCQM) Foundation, CH-8048 Zurich, Switzerland (2015) Chronic NSAID use and long-term decline of renal function in a prospective rheumatoid arthritis cohort study. Ann. Rheum. Dis. 74, 718-723.
  36. Morales, A. I., Detaille, D., Prieto, M., Puente, A., Briones, E., Arevalo, M., Leverve, X., Lopez-Novoa, J. M. and El-Mir, M. Y. (2010) Metformin prevents experimental gentamicin-induced nephropathy by a mitochondria-dependent pathway. Kidney Int. 77, 861-869.
  37. Navarro, V. J. and Senior, J. R. (2006) Drug-related hepatotoxicity. N. Engl. J. Med. 354, 731-739.
  38. Okabe, H., Hasunuma M. and Hashimoto, Y. (2003) The hepatic and intestinal metabolic activities of P450 in rats with surgery- and drug-induced renal dysfunction. Pharm. Res. 20, 1591-1594.
  39. Park, C. H., Tanaka, T., Kim, J. H., Cho, E. J., Park, J. C., Shibahara, N. and Yokozawa, T. (2011) Hepato-protective effects of loganin, iridoid glycoside from CorniFructus, against hyperglycemia-activated signaling pathway in liver of type 2 diabetic db/db mice. Toxicology 290, 14-21.
  40. Park, H. J., Bae, S. H. and Kim, S. H. (2021) Dose-independent pharmacokinetics of loganin in rats: effect of intestinal first-pass metabolism on bioavailability. J. Pharm. Investig. 51, 767-776.
  41. Salem, E. A., Salem, N. A., Kamel, M., Maarouf, A. M., Bissada, N. K., Hellstrom, W. J. and Eladl, M. (2010) Amelioration of gentamicin nephrotoxicity by green tea extract in uninephrectomized rats as a model of progressive renal failure. Ren. Fail. 32, 1210-1215.
  42. Siddik, Z. H., Newell, D. R., Boxall, F. E. and Harrap, K. R. (1987) The comparative pharmacokinetics of carboplatin and cisplatin in mice and rats. Biochem. Pharmacol. 36, 1925-1932.
  43. Sihvonen, S., Korpela, M., Mustonen, J., Laippala, P. and Pasternack, A. (2004) Renal disease as a predictor of increased mortality among patients with rheumatoid arthritis. Nephron. Clin. Pract. 96, c107-c114.
  44. Stojiljkovic, N., Veljkovic, S., Mihailovic, D., Stoiljkovic, M., Radenkovic, M., Rankovic, G. and Randjelovic, P. (2009) Protective effects of pentoxifylline treatment on gentamicin-induced nephrotoxicity in rats. Ren. Fail. 31, 54-61.
  45. Szentmihalyi, K., May, Z., Szenasi, G., Mathe, C., Sebesteny, A., Albert, M. and Blazovics, A. (2014) Cisplatin administration influences on toxic and non-essential element metabolism in rats. J. Trace Elem. Med. Biol. 28, 317-321.
  46. Teng, Z. Y., Cheng, X. L., Cai, X. T., Yang, Y., Sun, X. Y., Xu, J. D., Lu, W. G., Chen, J., Hu, C. P., Zhou, Q., Wang, X. N., Li, S. L. and Cao, P. (2015) Ancient chinese formula Qiong-Yu-Gao protects against cisplatin-induced nephrotoxicity without reducing anti-tumor activity. Sci. Rep. 5, 15592.
  47. Thomas, E., Symmons, D. P., Brewster, D. H., Black, R. J. and Macfarlane, G. J. (2003) National study of cause-specific mortality in rheumatoid arthritis, juvenile chronic arthritis, and other rheumatic conditions: a 20 year follow-up study. J. Rheumatol. 30, 958-965.
  48. Wilkinson, G. R. and Shand, D. G. (1975) A physiological approach to hepatic drug clearance. Clin. Pharmacol. Ther. 18, 377-390.
  49. Xu, H., Shen, J., Liu, H., Shi, Y., Li, L. and Wei, M. (2006) Morroniside and loganin extracted from Cornus officinalis have protective effects on rat mesangial cell proliferation exposed to advanced glycation end products by preventing oxidative stress. Can. J. Physiol. Pharmacol. 84, 1267-1273.
  50. Zhou, H., Hu, X., Li, N., Li, G., Sun, X., Ge, F., Jiang, J., Yao, J., Huang, D. and Yang, L. (2020) Loganetin and 5-fluorouracil synergistically inhibit the carcinogenesis of gastric cancer cells via down-regulation of the Wnt/β-catenin pathway. J. Cell Mol. Med. 24, 13715-13726.