Protective effect of piperine in ischemia-reperfusion induced acute kidney injury through inhibition of inflammation and oxidative stress

10.1016/j.jtcme.2019.07.002

Maryam Mohammadi；Houshang Najafi；Zeynab Mohamadi Yarijani；Gholamhasan Vaezi；Vida Hojati

Piperine ； Ischemia-reperfusion ； Acute kidney injury ； Inflammation ； Oxidative stress

Journal of Traditional and Complementary Medicine

10卷6期（2020 / 11 / 01）

570 - 576

英文

Background and aim: Renal ischemia-reperfusion is associated with inflammation and oxidative stress. As a major compound in black pepper, piperine has anti-inflammatory and anti-oxidative properties. In present study, the protective effects of oral administration of piperine in renal ischemia-reperfusion (IR) induced acute kidney injuries (AKI) were investigated. Experimental procedure: Male Wistar rats received piperine (10 or 20 mg/kg.bw) or vehicle for 10 days. The artery and vein of both kidneys were then clamped for 30 min, followed by a 24-h reperfusion period. Concentrations of creatinine and urea-nitrogen in descending aorta blood were measured, and malondialdehyde (MDA) and ferric reducing/antioxidant power (FRAP) levels were measured in kidney tissue to evaluate the oxidative stress. Inflammation was evaluated by measuring the TNF-α and ICAM-1 mRNA expression levels in renal cortical tissue using Real Time PCR method and counting leukocytes infiltration to interstitium. Further measured were tissue damages in H & E stained sections. Results: Renal IR reduced FRAP, while increasing the plasma concentrations of creatinine and ureanitrogen, tissue MDA level, TNF-α and ICAM-1 mRNA expressions, leukocyte infiltration and histopathologic injuries. Piperine administration significantly reduced the plasma concentrations of creatinine and urea-nitrogen, expression of pro-inflammatory factors, oxidative stress and renal histopathologic injuries. It is to be noted that 20 mg/kg dose was more effective. Conclusion: Our results suggest piperine protects the kidney against ischemia-reperfusion induced acute kidney injuries by its anti-inflammatory and anti-oxidative properties.

1. Abuelo, JG(2007).Normotensive ischemic acute renal failure.N Engl J Med.,357,797-805.
2. Akcay, A,Nguyen, Q,Edelstein, CL(2009).Mediators of inflammation in acute kidney injury.Mediat Inflamm,2009,137072.
3. Basile, DP,Anderson, M,Sutton, TA(2012).Pathophysiology of acute kidney injury.Comp Physiol,2,1303-1353.
4. Basile, DP,Yoder, MC(2014).Renal endothelial dysfunction in acute kidney ischemia reperfusion injury.Cardiovasc Haematol Disord - Drug Targets,14,3-14.
5. Becker, GJ,Hewitson, TD(2013).Animal models of chronic kidney disease: useful but not perfect.Nephrol Dial Transplant,28,2432-2438.
6. Bhat, BG,Chandrasekhara, N(1986).Studies on the metabolism of piperine: absorption, tissue distribution and excretion of urinary conjugates in rats.Toxicology,40,83-92.
7. Booranasubkajorn, S,Huabprasert, S,Wattanarangsan, J,Chotitham, P,Jutasompakorn, P,Laohapand, T(2017).Vasculoprotective and vasodilatation effects of herbal formula (Sahatsatara) and piperine in spontaneously hypertensive rats.Phytomedicine,24,148-156.
8. Chatterjee, PK,Patel, N,Sivarajah, A(2003).GW274150, a potent and highly selective inhibitor of iNOS, reduces experimental renal ischemia/reperfusion injury.Kidney Int,63,853-865.
9. Chen, GY,Nunez, G(2010).Sterile inflammation: sensing and reacting to damage.Nat Rev Immunol,10,826-837.
10. Devarajan, P(2006).Update on mechanisms of ischemic acute kidney injury.J Am Soc Nephrol,17,1503-1520.
11. Goligorsky, MS,Brodsky, SV,Noiri, E(2002).Nitric oxide in acute renal failure: NOS versus NOS.Kidney Int,61,855-861.
12. Hammad, AS,Ravindran, S,Khalil, A,Munusamy, S(2017).Structure-activity relationship of piperine and its synthetic amide analogs for therapeutic potential to prevent experimentally induced ER stress in vitro.Cell Stress Chaperones,22,417-428.
13. Han, Y,Chin, Tan, TM,Lim, LY(2008).In vitro and in vivo evaluation of the effects of piperine on P-gp function and expression.Toxicol Appl Pharmacol,230,283-289.
14. Hu, D,Wang, Y,Chen, Z(2015).The protective effect of piperine on dextran sulfate sodium induced inflammatory bowel disease and its relation with pregnane X receptor activation.J Ethnopharmacol,169,109-123.
15. Huls, M,Schoeber, JP,Verfaillie, CM(2010).Deficiency of either P-glycoprotein or breast cancer resistance protein protect against acute kidney injury.Cell Transplant,19,1195-1208.
16. Kelly, KJ,Williams, W,Colvin, RB(1996).Intercellular adhesion molecule-1-deficient mice are protected against ischemic renal injury.J Clin Investig,97,1056-1063.
17. Kim, HG,Han, EH,Jang, WS(2012).Piperine inhibits PMA-induced cyclo-oxygenase-2 expression through downregulating NF-κB, C/EBP and AP-1 signaling pathways in murine macrophages.Food Chem Toxicol,50,2342-2348.
18. Kinsey, GR,Li, L,Okusa, MD(2008).Inflammation in acute kidney injury.Nephron Exp Nephrol,109,e102-e107.
19. Kurts, C,Panzer, U,Anders, HJ,Rees, AJ(2013).The immune system and kidney disease: basic concepts and clinical implications.Nat Rev Immunol,13,738-753.
20. Lameire, N,Van Biesen, W,Vanholder, R(2005).Acute renal failure.Lancet,365,417-430.
21. Lee, CG,Kim, JG,Kim, HJ(2014).Discovery of an integrative network of microRNAs and transcriptomics changes for acute kidney injury.Kidney Int,86,943-953.
22. Ling, H,Edelstein, C,Gengaro, P(1999).Attenuation of renal ischemia-reperfusion injury in inducible nitric oxide synthase knockout mice.Am J Physiol Renal Physiol,46,F383-F390.
23. Liu, H,Bigler, SA,Henegar, JR,Baliga, R(2002).Cytochrome P450 2B1 mediates oxidant injury in puromycin-induced nephrotic syndrome.Kidney Int,62,868-876.
24. Mahmoudzadeh, L,Najafi, H,Changizi-Ashtiyani, S,Mohamadi yarijani, Z(2017).Anti-inflammatory and protective effects of Saffron extract in ischemia-reperfusion induced acute kidney injury.Nephrology,22,748-754.
25. Mohamadi Yarijani, Z,Godini, A,Madani, SH,Najafi, H(2018).Reduction of cisplatin-induced renal and hepatic side effects in rat through antioxidative and anti-inflammatory properties of Malva sylvestris L. extract.Biomed Pharmacother,106,1767-1774.
26. Mohamadi Yarijani, Z,Najafi, H,Shackebaeia, D,Madani, SH,Modarresi, M,Jassemid, SV(2019).Amelioration of renal and hepatic function, oxidative stress, inflammation and histopathologic damages by Malva sylvestris extract in gentamicin induced renal toxicity.Biomed Pharmacother,112,108635.
27. Mujumdar, AM,Dhuley, JN,Deshmukh, VK,Raman, PH,Naik, SR(1990).Anti-Inflammatory activity of piperine.Jpn J Med Sci Biol,43,95-100.
28. Najafi, H,Mohamadi Yarijani, Z,Changizi-Ashtiyani, S(2017).Protective effect of Malva sylvestris L. extract in ischemia-reperfusion induced acute kidney and remote liver injury.PLoS One,12,e0188270.
29. Rabb, H,Griffin, MD,McKay, DB(2016).Inflammation in AKI: current understanding, key questions, and knowledge gaps.J Am Soc Nephrol,27,371-379.
30. Reen, RK,Wiebel, FJ,Singh, J(1997).Piperine inhibits aflatoxin B1-induced cytotoxicity and genotoxicity in V79 Chinese hamster cells genetically engineered to express rat cytochrome P4502B1.J Ethnopharmacol,58,165-173.
31. Selvendiran, K,Thirunavukkarasu, C,Singh, JP,Padmavathi, R,Sakthisekaran, D(2005).Chemopreventive effect of piperine on mitochondrial TCA cycle and phase-I and glutathione-metabolizing enzymes in benzo(a)pyrene induced lung carcinogenesis in Swiss albino mice.Mol Cell Biochem,271,101-106.
32. Sudjarwo, SA,Eraiko, K,Sudjarwo, GW,Koerniasari(2017).Protective effects of piperine on lead acetate induced-nephrotoxicity in rats.Iran J Basic Med Sci.,20,227-231.
33. Taqvi, SI,Shah, AJ,Gilani, AH(2008).Blood pressure lowering and vasomodulator effects of piperine.J Cardiovasc Pharmacol,52,452-458.
34. Thurman, JM(2007).Triggers of inflammation after renal ischemia/reperfusion.Clin Immunol,123,7-13.
35. Vaibhav, K,Shrivastava, P,Javed, H(2012).Piperine suppresses cerebral ischemiareperfusion-induced inflammation through the repression of COX-2, NOS-2, and NF-κB in middle cerebral artery occlusion rat model.Mol Cell Biochem,367,73-84.
36. Vijayakumar, RS,Surya, D,Nalini, N(2004).Antioxidant efficacy of black pepper (Piper nigrum L.) and piperine in rats with high fat diet induced oxidative stress.Redox Rep,9,105-110.
37. Wang, W,Mitra, A,Poole, B(2004).Endothelial nitric oxide synthase-deficient mice exhibit increased susceptibility to endotoxin-induced acute renal failure.Am J Physiol Renal Physiol,287,F1044-F1048.
38. Wang-Sheng, C,Jie, A,Jian-Jun, L,Lan, H,Zeng-Bao, X,Chang-Qing, L(2017).Piperine attenuates lipopolysaccharide (LPS)-induced inflammatory responses in BV2 microglia.Int Immunopharmacol,42,44-48.
39. Wangsiripaisan, A,Gengaro, PE,Edelstein, CL,Schrier, RW(2001).Role of polymeric Tamm-Horsfall protein in cast formation: oligosaccharide and tubular fluid ions.Kidney Int,59,932-940.
40. Ying, X,Chen, X,Cheng, S,Shen, Y,Peng, L,Xu, HZ(2013).Piperine inhibits IL-β induced expression of inflammatory mediators in human osteoarthritis chondrocyte.Int Immunopharmacol,17,293-299.
41. Zou, AP,Li, N,Cowley, AW, Jr(2001).Production and actions of superoxide in the renal medulla.Hypertension,37,547-553.