Protective effects of piperine on lead acetate induced-nephrotoxicity in rats

Document Type : Original Article


1 Department of Pharmacology, Faculty of Veterinary Medicine, Airlangga University, Surabaya 60115 Indonesia

2 Department of Conservative Dentistry, Faculty of Dentistry, Airlangga University, Surabaya 60115 Indonesia

3 Department of Pharmacy Biology, Faculty of Pharmacy, Hang Tuah University, Surabaya 60115 Indonesia

4 Study Program of Environmental Health, Polytechnic of Health, Surabaya 60115 Indonesia


Objective(s): In this study, we investigated the protective effects of piperine on lead acetate-induced renal damage in rat kidney tissue.
Materials and Methods: Forty male rats were divided into 5 groups: negative control (rats were given aquadest daily), positive control (rats were given lead acetate 30 mg/kg BW orally once a day for 60 days), and the treatment group (rats were given piperine 50 mg; 100 mg and 200 mg/kg BW orally once a day for 65 days, and on 5th day, were given lead acetate 30 mg/kg BW one hr after piperine administration for 60 days). On day 65 levels of blood urea nitrogen (BUN), creatinine, malondialdehyde (MDA), Superoxide Dismutase (SOD), and Glutathione Peroxidase (GPx) were measured. Also, kidney samples were collected for histopathological studies.
Results: The results revealed that lead acetate toxicity induced a significant increase in the levels of BUN, creatinine, and MDA; moreover, a significant decrease in SOD and GPx. Lead acetate also altered kidney histopathology (kidney damage, necrosis of tubules) compared to the negative control. However, administration of piperine significantly improved the kidney histopathology, decreased the levels of BUN, creatinine, and MDA, and also significantly increased the SOD and GPx in the kidney of lead acetate-treated rats.
Conclusion: From the results of this study it was concluded that piperine could be a potent natural herbal product exhibiting nephroprotective effect against lead acetate induced nephrotoxicity in rats.


1. Gagan F, Deepesh G, Archana T. Toxicity of lead: A review with recent updates. Interdiscip Toxicol 2012; 5:47-58.
2. Ani M, Aparajita C, Rituparna G, Mahitosh S. Protective effects of selenium and zinc on the brain acetyl cholinesterase activity in lead intoxified rat. Res Pharm Sci 2006; 2:80-84.
3. Vaziri ND, Gonick HC. Cardiovascular effects of lead exposure. Indian J Med Res 2008;128:426-435.
4. Jia Q, Ha X, Yang Z, Hui L, Yang X. Oxidative stress: a possible mechanism for lead-induced apoptosis and nephrotoxicity. Toxicol Mech Methods 2012; 22:705-710
5. Mohamed OI, El-Nahas AF, El-Sayed YS, Ashry KM. Ginger extract modulates Pb-induced hepatic oxidative stress and expression of antioxidant gene transcripts in rat liver. Pharm Biol 2015:1-9
6. Adhikari NN, Sinha R, Narayan, Saxena DK. Lead-induced cell death in testes of young rats. J Appl Toxicol 2001;21:275-277.
7. Patrick L. Lead toxicity part II: The role of free radical damage and use of antioxidants in the pathology and treatment of lead toxicity. Altern Med Rev 2006; 11:114-127.
8. Hussein SA, Mohammed RR, Ali AH, Protective effects of alpha-lipoic acid against lead-induced oxidative stress in erythrocytes of rats. Benha Vet Med J 2014; 27: 382‐395.
9. Xu J, Lian LJ, Wu C, Wang XF, Fu WY. Lead induces oxidative stress, DNA damage and alteration of p53, Bax and Bcl-2 expressions in mice. Food Chem Toxicol 2008; 46:1488-1494.
10. Mervat HG, Nabela IE, Mohamed MAH, Gihan GM. Efficacy of Curcumin on Lead Induced Nephrotoxicity in Female Albino Rats. J Am Sci 2012; 8:78-82.
11. Kosem N, Han YH, Moongkarndi P. Antioxidant and cytoprotective activities of methanolic extract from Garcinia mangostana Hulls. Science Asia 2007; 33: 283-292.
12. Ibrahim NM, Eweis EA, El-Beltagi HS, Abdel Mobdy YE. Effect of lead acetate toxicity on experimental male albino rat. Asian Pac J Trop Biomed 2012;2: 41-46.
13. Jackie T, Haleagrahara N, Chakravarthi S. Antioxidant effects of Etlingera elatior flower extract against lead acetate induced perturbations in free radical scavenging enzymes and lipid peroxidation in rats. BMC Research Notes 2011; 4:67-75.
14. Wang J, Yang Z, Liu L, Xuezhong Liu ZL. Protective effect of naringenin against lead-induced oxidative stress in rats. Biol Trace Elem Res 2012; 146:354-359.
15. Aziz FM, Maulood IM, Chawsheen MA. Effects of melatonin, vitamin C and E alone or in combination on lead-induced injury in liver and kidney organs of rats. Pakistan J Zool 2014; 46: 1425-1431.
16. Chen L,Yang X, Jiao H. Tea catechins protect against lead-induced ROS formation, mitochondrial dysfunction, and calcium dysregulation in PC12 cells. Chem Res Toxicol 2003; 16:1155-1161.
17. Hanan M, El-Latief A. Protective effect of quercetin and or zinc against lead toxicity on rat testes. Global J Pharmacol 2015; 9: 366-376.
18. Yadala P, Viswanathswamy AHM. In vitro antioxidant and cytotoxic activity of rutin and piperine and their synergistic effect. Int J Pharm Pharm Sci 2016; 8: 78-82.
19. Sudjarwo SA. The potency of piperine as antiinflamatory and analgesic in rats and mice. Folia Medica Indonesiana 2005; 41:190-194.
20. Taqvi SI, Gilani AH. Blood pressure lowering and vasomodulator effects of piperine. J Cardiovasc Pharmacol 2008; 52:452-458.
21. Doucette CD, Hilchie AL. Piperine, a dietary phytochemical, inhibits angiogenesis. J NutrBiochem 2013; 24:231-239.
22. Sharma S, Kalia NP, Suden P. Protective efficacy of piperine against Mycobacterium tuberculosis. Tuberculosis 2014;94:389-396.
23. Aslam M, Ahmad ST, Dayal R, Nafees S, Singh S. Nephroprotective action of Peucedanum grande against cadmium chloride induced renal toxicity in wistar rats. Excli J 2012; 11:444-452.
24. Suji Arivazhagan JJ, Vimalastalin R. Nephroprotective activity of Aristolochia indica leaf extract against gentamicin induced renal dysfunction. Inter J of Res in Biochem Biophysics 2014; 4:13-18.
25. Hamadouche NA, Lazeb H, Kaddouri A, Aoues A, Ameliorated effects of Green tea extract on lead induced kidney toxicity in rats. Algerian J Nat Prod 2015; 3:130-137.
26. Hsu PC, Guo YL. Antioxidant nutrients and lead toxicity. Toxicology 2002; 180:33-44.
27. Ishiaq O, Adeagbo AG, Henshaw N. Effect of a natural antioxidant fruit - tomatoes (Lycoperscion esculentium) as a potent nephroprotective agent in lead induced nephrotoxicity in rat. J. Pharmacog. Phytother 2011; 3:63-66.
28. Newairy AS, Abdou HM. Protective role of flax lignans against lead acetate induced oxidative damage and hyperlipidemia in rats. Food Chem Toxicol 2009; 47:813-818.
29. Moussa SA, Bashandy SA. Biophysical and biochemical changes in the blood of rats exposed to lead toxicity. Rom J Biophys 2008;18:123-133.