Skip to main content

Diallyl disulfide attenuates acetaminophen-induced renal injury in rats

Abstract

This study investigated the protective effects of diallyl disulfide (DADS) against acetaminophen (AAP)-induced acute renal injury in male rats. We also investigated the effects of DADS on kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NCAL), which are novel biomarkers of nephrotoxicity in renal tissues, in response to AAP treatment. The following four experimental groups were evaluated: (1) vehicle control, (2) AAP (1,000 mg/kg), (3) AAP&DADS, and (4) DADS (50 mg/kg/day). AAP treatment caused acute kidney injury evidenced by increased serum blood urea nitrogen (BUN) levels and histopathological alterations. Additionally, Western blot and immunohistochemistry analysis showed increased expression of KIM-1 and NCAL proteins in renal tissues of AAP-treated rats. In contrast, DADS pretreatment significantly attenuated the AAP-induced nephrotoxic effects, including serum BUN level and expression of KIM-1 and NCAL proteins. Histopathological studies confirmed the renoprotective effect of DADS. The results suggest that DADS prevents AAP-induced acute nephrotoxicity, and that KIM-1 and NCAL may be useful biomarkers for the detection and monitoring of acute kidney injury associated with AAP exposure.

References

  1. Kanno S, Tomizawa A, Hiura T, Osanai Y, Kakuta M, Kitajima Y, Koiwai K, Ohtake T, Ujibe M, Ishikawa M. Melatonin protects on toxicity by acetaminophen but not on pharmacological effects in mice. Biol Pharm Bull 2006; 29(3): 472–476.

    Article  CAS  Google Scholar 

  2. Hengy B, Hayi-Slayman D, Page M, Christin F, Baillon JJ, Ber CE, Allaouchiche B, Rimmele T. Acute renal failure after acetaminophen poisoning: report of three cases. Can J Anaesth 2009; 56(10): 770–774.

    Article  Google Scholar 

  3. Ghosh J, Das J, Manna P, Sil PC. Acetaminophen induced renal injury via oxidative stress and TNF-alpha production: therapeutic potential of arjunolic acid. Toxicology 2010; 268(1-2.: 8–18.

    CAS  PubMed  Google Scholar 

  4. Singh VP, Singh N, Jaggi AS. A review on renal toxicity profile of common abusive drugs. Korean J Physiol Pharmacol 2013; 17(4): 347–357.

    Article  CAS  Google Scholar 

  5. Schnellman RG Toxic responses of the kidney. In: Casarett & DoulPs Toxicology: The Basic Science of Poisons (Klassen CD, ed), 6th ed., McGraw-Hill Medical Publishing Division, New York, 2001; pp 491–514.

    Google Scholar 

  6. Mediae B, Rovcanin B, Vujovic KS, Obradovic D, Duric D, Prostran M. Evaluation of Novel Biomarkers of Acute Kidney Injury: The Possibilities and Limitations. Curr Med Chem 2016; 23(19): 1981–1997.

    Article  Google Scholar 

  7. Schrezenmeier EV, Barasch J, Budde K, Westhoff T, Schmidt-Ott KM. Biomarkers in acute kidney injury - pathophysiological basis and clinical performance. Acta Physiol (Oxf) 2016; 30: 12764.

    Google Scholar 

  8. Ichimura T, Hung CC, Yang SA, Stevens JL, Bonventre JV. Kidney injury molecule-1: a tissue and urinary biomarker for nephrotoxicant-induced renal injury. Am J Physiol Renal Physiol 2004; 286(3): F552–563.

    Article  Google Scholar 

  9. Huo W, Zhang K, Nie Z, Li Q, Jin F. Kidney injury molecule-1 (KIM-1): a novel kidney-specific injury molecule playing potential double-edged functions in kidney injury. Transplant Rev (Orlando) 2010; 24(3): 143–146.

    Article  Google Scholar 

  10. Bolignano D, Donato V, Coppolino G, Campo S, Buemi A, Lacquaniti A, Buemi M. Neutrophil gelatinase-associated lipocalin (NGAL) as a marker of kidney damage. Am J Kidney Dis 2008; 52(3): 595–605.

    Article  CAS  Google Scholar 

  11. Mishra J, Ma Q, Kelly C, Mitsnefes M, Mori K, Barasch J, Devarajan P. Kidney NGAL is a novel early marker of acute injury following transplantation. Pediatr Nephrol 2006; 21(6): 856–863.

    Article  Google Scholar 

  12. Soni SS, Cruz D, Bobek I, Chionh CY, Nalesso F, Lentini P, de Cal M, Corradi V, Virzi G, Ronco C. NGAL: a biomarker of acute kidney injury and other systemic conditions. Int Urol Nephrol 2010; 42(1): 141–150.

    Article  CAS  Google Scholar 

  13. Han WK, Bonventre JV. Biologic markers for the early detection of acute kidney injury. Curr Opin Crit Care 2004; 10(6): 476–482.

    Article  Google Scholar 

  14. Mishra J, Ma Q, Prada A, Mitsnefes M, Zahedi K, Yang J, Barasch J, Devarajan P. Identification of neutrophil gelatinase- associated lipocalin as a novel early urinary biomarker for ischemic renal injury. J Am Soc Nephrol 2003; 14(10): 2534–2543.

    Article  CAS  Google Scholar 

  15. Ding H, He Y, Li K, Yang J, Li X, Lu R, Gao W. Urinary neutrophil gelatinase-associated lipocalin (NGAL) is an early biomarker for renal tubulointerstitial injury in IgA nephropathy. Clin Immunol 2007; 123(2): 227–234.

    Article  CAS  Google Scholar 

  16. Pedraza-Chaverrí J, Gonzalez-Orozco AE, Maldonado PD, Barrera D, Medina-Campos ON, Hernandez-Pando R. Diallyl disulfide ameliorates gentamicin-induced oxidative stress and nephropathy in rats. Eur J Pharmacol 2003; 473(1): 71–78.

    Article  Google Scholar 

  17. Chiarandini Fiore JP, Fanelli SL, de Ferreyra EC, Castro JA. Diallyl disulfide prevention of cis-Diamminedichloroplatinum-induced nephrotoxicity and leukopenia in rats: potential adjuvant effects. Nutr Cancer 2008; 60(6): 784–791.

    Article  CAS  Google Scholar 

  18. Kim SH, Lee IC, Baek HS, Shin IS, Moon C, Bae CS, Kim SH, Kim JC, Kim HC. Mechanism for the protective effect of diallyl disulfide against cyclophosphamide acute urotoxicity in rats. Food Chem Toxicol 2014; 64: 110–118.

    Article  CAS  Google Scholar 

  19. Lee IC, Kim SH, Baek HS, Moon C, Kang SS, Kim SH, Kim YB, Shin IS, Kim JC. The involvement of Nrf2 in the protective effects of diallyl disulfide on carbon tetrachloride-induced hepatic oxidative damage and inflammatory response in rats. Food Chem Toxicol 2014; 63: 174–185.

    Google Scholar 

  20. Das J, Ghosh J, Manna P, Sil PC. Taurine protects acetaminophen- induced oxidative damage in mice kidney through APAP urinary excretion and CYP2E1 inactivation. Toxicology 2010; 269(1): 24–34.

    Article  CAS  Google Scholar 

  21. Kumanogoh A, Marukawa S, Suzuki K, Takegahara N, Watanabe C, Ch’ng E, Ishida I, Fujimura H, Sakoda S, Yoshida K, Kikutani H. Class IV semaphorin Sema4A enhances T-cell activation and interacts with Tim-2. Nature 2002; 419(6907): 629–633.

    Article  CAS  Google Scholar 

  22. Monney L, Sabatos CA, Gaglia JL, Ryu A, Waldner H, Chernova T, Manning S, Greenfield EA, Coyle AJ, Sobel RA, Freeman GJ, Kuchroo VK. Thl-specific cell surface protein Tim-3 regulates macrophage activation and severity of an autoimmune disease. Nature 2002; 415(6871): 536–541.

    Article  CAS  Google Scholar 

  23. Ichimura T, Bonventre JV, Bailly V, Wei H, Hession CA, Cate RL, Sanicola M. Kidney injury molecule-1 (KIM-1), a putative epithelial cell adhesion molecule containing a novel immunoglobulin domain, is up-regulated in renal cells after injury. J Biol Chem 1998; 273(7): 4135–4142.

    Article  CAS  Google Scholar 

  24. Van Klinken BJ, Dekker J, Buller HA, Einerhand AW. Mucin gene structure and expression: protection vs. adhesion. Am J Physiol 1995; 269: G613–627.

    Google Scholar 

  25. Xu S, Venge P. Lipocalins as biochemical markers of disease. Biochim Biophys Acta 2000; 1482: 298–307.

    Article  CAS  Google Scholar 

  26. Supavekin S, Zhang W, Kucherlapati R, Kaskel FJ, Moore LC, Devarajan P. Differential gene expression following early renal ischemia/reperfusion. Kidney Int 2003; 63(5): 1714–1724.

    Article  CAS  Google Scholar 

  27. Vaidya VS, Ramirez V, Ichimura T, Bobadilla NA, Bonventre JV. Urinary kidney injury molecule-1: a sensitive quantitative biomarker for early detection of kidney tubular injury. Am J Physiol Renal Physiol 2006; 290(2): F517–529.

    Article  Google Scholar 

  28. Hoffmann D, Adler M, Vaidya VS, Rached E, Mulrane L, Gallagher WM, Callanan JJ, Gautier JC, Matheis K, Staedtler F, Dieterle F, Brandenburg A, Sposny A, Hewitt P, Ellinger- Ziegelbauer H, Bonventre JV, Dekant W, Mally A. Performance of novel kidney biomarkers in preclinical toxicity studies. Toxicol Sci 2010; 116(1): 8–22.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jong-Choon Kim.

Rights and permissions

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://doi.org/creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Shin, JY., Han, JH., Ko, JW. et al. Diallyl disulfide attenuates acetaminophen-induced renal injury in rats. Lab Anim Res 32, 200–207 (2016). https://doi.org/10.5625/lar.2016.32.4.200

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.5625/lar.2016.32.4.200

Keywords