Pomegranate protects renal proximal tubules during gentamicin induced-nephrotoxicity in rats
DOI:
https://doi.org/10.22317/jcms.v5i1.522Keywords:
Nephrotoxicity, Pomegranate, gentamicin, anti-oxidant capacityAbstract
Objective: The aim of present study was to evaluate the nephroprotective effect of pomegranate in gentamicin induced-nephrotoxicity in rats.
Methods: Thirty Sprague Dawley Male rat were used, which randomly divided into 3 groups, 10 rats in each group. Group1 (n=10): Rats treated with distilled water for 12 days.Group2 (n=10): Rats treated with distilled water + Gentamicin .Group3 (n=10): Rats treated with pomegranate + gentamicin. Blood urea, serum creatinine, serum malondialdehde (MDA), superoxide dismutase (SOD) , glutathione reductase (GSH) , Neutrophil Gelatinase Associated Lipocalin (NGAL) , kidney injury molecules (KIM-1) and Cystatin-c were measured .
Results: Blood urea and serum creatinine were significantly elevated in gentamicin group compared to the control p=0.007 and p=0.04 respectively. Also estimated GFR was significantly decreased in gentamicin group compared to the control p=0.04. Cystatin-c serum level and MDA serum level were increased but SOD and GSH were decreased insignificantly in gentamicin group compared to the control p>0.05. Pomegranate reduced blood urea significantly p=0.002. Pomegranate improves endogenous anti-oxidant capacity since; it increase GSH significantly compared to gentamicin group p=0.02. There were insignificant effects on MDA and SOD. Moreover, pomegranate reduce serum levels of KIM-1and NGAL in gentamicin group p<0.05.
Conclusion: Pomegranate attenuates gentamicin induced-nephrotoxicity through potentiation of endogenous anti-oxidant capacity and inhibition of inflammatory pathway.
References
1. Tiong HY , Huang P, Xiong S, Li Y, Vathsala A, Zink D. Drug-induced nephrotoxicity: clinical impact and preclinical in vitro models. Mol Pharm. 2014; 7; 11(7):1933-48.
2. Ennulat D , Ringenberg M , Frazier KS . Toxicologic Pathology Forum Opinion Paper : Recommendations for a Tiered Approach to Nonclinical Mechanistic Nephrotoxicity Evaluation. Toxicol Pathol. 2018 ;26:192623318788302.
3. Brocca A, Virzì GM , Pasqualin C , Pastori S , Marcante S , et al . Cardiorenal syndrome type 5: in vitro cytotoxicity effects on renal tubular cells and inflammatory profile. Anal Cell Pathol (Amst). 2015;2015:469461.
4. Kim SY , Moon A. Drug-induced nephrotoxicity and its biomarkers. Biomol Ther (Seoul). 2012 ;20(3):268-72.
5. A V , S A , Kuriakose J , Midhun SJ , Jyothis M , Latha MS . Protective effect of Rotula aquatica Lour against gentamicin induced oxidative stress and nephrotoxicity in Wistar rats. Biomed Pharmacother. 2018, 18;106:1188-1194.
6. Moffett BS, Morris J, Galati M , Munoz FM , Arikan AA . Population Pharmacokinetic Analysis of Gentamicin in Pediatric Extracorporeal Membrane Oxygenation. Ther Drug Monit. 2018 ; 26.
7. Ge S , Beechinor RJ , Hornik CP Standing JF , Zimmerman K , Cohen-Wolkowiez M, et al. External Evaluation of a Gentamicin Infant Population Pharmacokinetic Model Using Data from a National Electronic Health Record Database. Antimicrob Agents Chemother. 2018 , 18. pii: AAC.00669-18.
8. Aly HAA , Hassan MH . Potential testicular toxicity of gentamicin in adult rats. Biochem Biophys Res Commun. 2018 ,26;497(1):362-367.
9. Moreira MA , Nascimento MA , Bozzo TA , Cintra A , da Silva SM , Dalboni MA , et al. Ascorbic acid reduces gentamicin-induced nephrotoxicity in rats through the control of reactive oxygen species. Clin Nutr. 2014;33(2):296-301.
10. Magee PJ Rowland IR. Phyto-oestrogens, their mechanism of action: current evidence for a role in breast and prostate cancer. Br J Nutr. 2004 ;91(4):513-31.
11. Najaf Najafi M , Ghazanfarpour M . Effect of phytoestrogens on sexual function in menopausal women: a systematic review and meta-analysis. Climacteric. 2018 ; 29:1-9.
12. Huber R, Gminski R, Tang T, Weinert T, Schulz S, Linke-Cordes M, et al. Pomegranate (Punica granatum) Seed Oil for Treating Menopausal Symptoms: An Individually Controlled Cohort Study. Altern Ther Health Med. 2017 ;23(2):28-34.
13. Akhtar S , Ismail T , Fraternale D , Sestili P . Pomegranate peel and peel extracts: chemistry and food features. Food Chem. 2015 , 1;174:417-25.
14. Al-Kuraishy HM , Al-Gareeb AI . Potential Effects of Pomegranate on Lipid Peroxidation and Proinflammatory Changes in Daunorubicin-induced Cardiotoxicity in Rats.Int J Prev Med. 2016 ; 20;7:85.
15. Rasheed Z , Akhtar N, Anbazhagan AN, Ramamurthy S, Shukla M, Haqqi TM. Polyphenol-rich pomegranate fruit extract (POMx) suppresses PMACI-induced expression of pro-inflammatory cytokines by inhibiting the activation of MAP Kinases and NF-kappaB in human KU812 cells. J Inflamm (Lond). 2009 ,8;6:1.
16. Kim YE , Hwang CJ , Lee HP , Kim CS , Son DJ , Ham YW , et al. Inhibitory effect of punicalagin on lipopolysaccharide-induced neuroinflammation, oxidative stress and memory impairment via inhibition of nuclear factor-kappaB. Neuropharmacology. 2017 ,1;117:21-32.
17. Mansouri E , Basgen J , Saremy S . The effects of pomegranate extract on normal adult rat kidney: A stereological study. Vet Res Forum. 2016;7(1):1-6.
18. Singh AP , Junemann A, Muthuraman A, Jaggi AS, Singh N, Grover K, Dhawan R. Animal models of acute renal failure. Pharmacol Rep. 2012;64(1):31-44.
19. Gacka E , Życzkowski M , Bogacki R , Paradysz A , Hyla-Klekot L . The Usefulness of Determining Neutrophil Gelatinase-Associated Lipocalin ConcentrationExcreted inthe Urine inthe Evaluation of Cyclosporine A Nephrotoxicity in Children with Nephrotic Syndrome. Dis Markers. 2016;2016:6872149.
20. Abd-Elhamid TH , Elgamal DA , Ali SS , Ali FEM , Hassanein EHM , El-Shoura EAM , et al. Reno-protective effects of ursodeoxycholic acid against gentamicin-induced nephrotoxicitythrough modulation of NF-κB, eNOS and caspase-3 expressions. Cell Tissue Res. 2018 ; 4.
21. Helal MG , Zaki MMAF , Said E . Nephroprotective effect of saxagliptin against gentamicin-induced nephrotoxicity, emphasis on anti-oxidant, anti-inflammatory and anti-apoptic effects. Life Sci. 2018 ;14. pii: S0024-3205(18)30398-9.
22. Ibraheem ZO , Basir R , Aljobory AKh , Ibrahim OE , Alsumaidaee A , Yam MF . Impact of gentamicin coadministration along with high fructose feeding on progression of renal failure and metabolic syndrome in Sprague-Dawley rats. Biomed Res Int. 2014;2014:823879.
23. Alarifi S, Al-Doaiss A, Alkahtani S, et al. Blood chemical changes and renal histological alterations induced by gentamicin in rats. Saudi J Biol Sci. 2012;19:103–110.
24. Hajihashemi S , Jafarian T , Ahmadi M , Rahbari A , Ghanbari F . Ameliorative Effects of Zataria Multiflora Hydro-Alcoholic extract on Gentamicin InducedNephrotoxicity in Rats. Drug Res (Stuttg). 2018;68(7):387-394.
25. Luo QH , Chen ML, Sun FJ, Chen ZL, Li MY, Zeng W, et al. KIM-1 and NGAL as biomarkers of nephrotoxicity induced by gentamicin in rats. Mol Cell Biochem. 2014;397(1-2):53-60.
26. C. C. Szeto, B. C. H. Kwan, K. B. Lai et al. Urinary expression of kidney injury markers in renal transplant recipients, Clinical Journal of the American Society of Nephrology, vol. 5, no. 12, pp. 2329–2337, 2010.
27. K. Makris, N. Markou, E. Evodia et al., “Urinary neutrophil gelatinase-associated lipocalin (NGAL) as an early marker of
acute kidney injury in critically ill multiple trauma patients,†Clinical Chemistry and LaboratoryMedicine, vol. 47,no. 1, pp. 79–82, 2009.
28. Geus H. R. H. Bakker de.Neutrophil gelatinase-associated lipocalin at ICU admission predicts for acute kidney injury in adult patients,†American Journal of Respiratory and Critical Care Medicine, vol. 183, no. 7, pp. 907–914, 2011.
29. Kader C , Sunbul M , Das YK , Yarim M , Bedir A , Karaca E , et al Telbivudine attenuates gentamicin-induced kidney injury in rats. Int J Antimicrob Agents. 2017 ;49(5):595-602.
30. Al Suleimani YM , Abdelrahman AM , Karaca T , Manoj P , Ashique M , Nemmar A , et al. The effect of the dipeptidyl peptidase-4 inhibitor sitagliptin on gentamicin nephrotoxicity in mice.Biomed Pharmacother. 2018;97:1102-1108.
31. Alimoradian A , Changizi-Ashtiyani S, Ghiasabadi Farahani A, Kheder L, Rajabi R, Sharifi A. Protective Effects of Pomegranate Juice on Nephrotoxicity Induced by Captopril and Gentamicinin Rats. Iran J Kidney Dis. 2017;11(6):422-429.
32. Primarizky H , Yuniarti WM , Lukiswanto BS . Benefits of pomegranate (Punica granatum Linn) fruit extracts to weight changes, total protein, and uric acid in white rats (Rattus norvegicus) as an animal model of acute renal failure. Send to Vet World. 2016 ;9(11):1269-1274.
33. Boroushaki MT , Asadpour E , Sadeghnia HR , Dolati K . Effect of pomegranate seed oil against gentamicin -induced nephrotoxicity in rat. J Food Sci Technol. 2014;51(11):3510-4.
34. Cekmen M , Otunctemur A, Ozbek E, Cakir SS, Dursun M, Polat EC, et al. Pomegranate extract attenuates gentamicin-induced nephrotoxicity in rats by reducing oxidative stress. Ren Fail. 2013; 35(2):268-74.
35. El-Arabey AA . Negative Response of Phytoestrogens of Pomegranate Flower Extract against Cisplatin-induced Nephrotoxicity in Female Rats. Int J Prev Med. 2016 Jun 27;7:89.
36. Motamedi F , Nematbakhsh M , Monajemi R , Pezeshki Z , Talebi A , Zolfaghari B , et al. Effect of pomegranate flower extract on cisplatin-induced nephrotoxicity in rats. J Nephropathol. 2014;3(4):133-8.
37. Nematbakhsh M , Ebrahimian S, Tooyserkani M, Eshraghi-Jazi F, Talebi A, Ashrafi F. Gender difference in Cisplatin-induced nephrotoxicity in a rat model: greater intensity of damage in male than female. Nephrourol Mon. 2013;5(3):818-21.
38. Boroushaki MT , Asadpour E , Sadeghnia HR , Dolati K . Effect of pomegranate seed oil against gentamicin -induced nephrotoxicity in rat. J Food Sci Technol. 2014 ;51(11):3510-4.
39. Cekmen M , Otunctemur A, Ozbek E, Cakir SS, Dursun M, Polat EC, et al. Pomegranate extract attenuates gentamicin-induced nephrotoxicity in rats by reducing oxidative stress. Ren Fail. 2013;35(2):268-74.
40. Zhang L, Yang X, Zhang Y, Wang L, Zhang R. In vitro antioxidant properties of different parts of pomegranate flowers. Food Bioprod Process. 2011;89:234–40.
41. Jang A, Srinivasan P, Lee NY, Song HP, Lee JW, Lee M. et al. Comparison of hypolipidemic activity of synthetic gallic acid–linoleic acid ester with mixture of gallic acid and linoleic acid, gallic acid, and linoleic acid on high-fat diet induced obesity in C57BL/6 Cr Slc mice. Chem Biol Interact. 2008;174:109–17.
42. Azarkish F, Nematbakhsh M, Fazilati M, Talebi A, Pilehvarian AA, Pezeshki Z. et al. N-acetylcysteine Prevents Kidney and Lung Disturbances in Renal Ischemia/Reperfusion Injury in Rat. Int J Prev Med. 2013;4:1139.
43. Frutos P, Hervas G, Giraldez FJ, Mantecon AR. Frutos P, Hervas G, Giraldez FJ, Mantecon ARReviewTannins and ruminant nutrition. Span J Agric Res. 2004;2:191–202.
2. Ennulat D , Ringenberg M , Frazier KS . Toxicologic Pathology Forum Opinion Paper : Recommendations for a Tiered Approach to Nonclinical Mechanistic Nephrotoxicity Evaluation. Toxicol Pathol. 2018 ;26:192623318788302.
3. Brocca A, Virzì GM , Pasqualin C , Pastori S , Marcante S , et al . Cardiorenal syndrome type 5: in vitro cytotoxicity effects on renal tubular cells and inflammatory profile. Anal Cell Pathol (Amst). 2015;2015:469461.
4. Kim SY , Moon A. Drug-induced nephrotoxicity and its biomarkers. Biomol Ther (Seoul). 2012 ;20(3):268-72.
5. A V , S A , Kuriakose J , Midhun SJ , Jyothis M , Latha MS . Protective effect of Rotula aquatica Lour against gentamicin induced oxidative stress and nephrotoxicity in Wistar rats. Biomed Pharmacother. 2018, 18;106:1188-1194.
6. Moffett BS, Morris J, Galati M , Munoz FM , Arikan AA . Population Pharmacokinetic Analysis of Gentamicin in Pediatric Extracorporeal Membrane Oxygenation. Ther Drug Monit. 2018 ; 26.
7. Ge S , Beechinor RJ , Hornik CP Standing JF , Zimmerman K , Cohen-Wolkowiez M, et al. External Evaluation of a Gentamicin Infant Population Pharmacokinetic Model Using Data from a National Electronic Health Record Database. Antimicrob Agents Chemother. 2018 , 18. pii: AAC.00669-18.
8. Aly HAA , Hassan MH . Potential testicular toxicity of gentamicin in adult rats. Biochem Biophys Res Commun. 2018 ,26;497(1):362-367.
9. Moreira MA , Nascimento MA , Bozzo TA , Cintra A , da Silva SM , Dalboni MA , et al. Ascorbic acid reduces gentamicin-induced nephrotoxicity in rats through the control of reactive oxygen species. Clin Nutr. 2014;33(2):296-301.
10. Magee PJ Rowland IR. Phyto-oestrogens, their mechanism of action: current evidence for a role in breast and prostate cancer. Br J Nutr. 2004 ;91(4):513-31.
11. Najaf Najafi M , Ghazanfarpour M . Effect of phytoestrogens on sexual function in menopausal women: a systematic review and meta-analysis. Climacteric. 2018 ; 29:1-9.
12. Huber R, Gminski R, Tang T, Weinert T, Schulz S, Linke-Cordes M, et al. Pomegranate (Punica granatum) Seed Oil for Treating Menopausal Symptoms: An Individually Controlled Cohort Study. Altern Ther Health Med. 2017 ;23(2):28-34.
13. Akhtar S , Ismail T , Fraternale D , Sestili P . Pomegranate peel and peel extracts: chemistry and food features. Food Chem. 2015 , 1;174:417-25.
14. Al-Kuraishy HM , Al-Gareeb AI . Potential Effects of Pomegranate on Lipid Peroxidation and Proinflammatory Changes in Daunorubicin-induced Cardiotoxicity in Rats.Int J Prev Med. 2016 ; 20;7:85.
15. Rasheed Z , Akhtar N, Anbazhagan AN, Ramamurthy S, Shukla M, Haqqi TM. Polyphenol-rich pomegranate fruit extract (POMx) suppresses PMACI-induced expression of pro-inflammatory cytokines by inhibiting the activation of MAP Kinases and NF-kappaB in human KU812 cells. J Inflamm (Lond). 2009 ,8;6:1.
16. Kim YE , Hwang CJ , Lee HP , Kim CS , Son DJ , Ham YW , et al. Inhibitory effect of punicalagin on lipopolysaccharide-induced neuroinflammation, oxidative stress and memory impairment via inhibition of nuclear factor-kappaB. Neuropharmacology. 2017 ,1;117:21-32.
17. Mansouri E , Basgen J , Saremy S . The effects of pomegranate extract on normal adult rat kidney: A stereological study. Vet Res Forum. 2016;7(1):1-6.
18. Singh AP , Junemann A, Muthuraman A, Jaggi AS, Singh N, Grover K, Dhawan R. Animal models of acute renal failure. Pharmacol Rep. 2012;64(1):31-44.
19. Gacka E , Życzkowski M , Bogacki R , Paradysz A , Hyla-Klekot L . The Usefulness of Determining Neutrophil Gelatinase-Associated Lipocalin ConcentrationExcreted inthe Urine inthe Evaluation of Cyclosporine A Nephrotoxicity in Children with Nephrotic Syndrome. Dis Markers. 2016;2016:6872149.
20. Abd-Elhamid TH , Elgamal DA , Ali SS , Ali FEM , Hassanein EHM , El-Shoura EAM , et al. Reno-protective effects of ursodeoxycholic acid against gentamicin-induced nephrotoxicitythrough modulation of NF-κB, eNOS and caspase-3 expressions. Cell Tissue Res. 2018 ; 4.
21. Helal MG , Zaki MMAF , Said E . Nephroprotective effect of saxagliptin against gentamicin-induced nephrotoxicity, emphasis on anti-oxidant, anti-inflammatory and anti-apoptic effects. Life Sci. 2018 ;14. pii: S0024-3205(18)30398-9.
22. Ibraheem ZO , Basir R , Aljobory AKh , Ibrahim OE , Alsumaidaee A , Yam MF . Impact of gentamicin coadministration along with high fructose feeding on progression of renal failure and metabolic syndrome in Sprague-Dawley rats. Biomed Res Int. 2014;2014:823879.
23. Alarifi S, Al-Doaiss A, Alkahtani S, et al. Blood chemical changes and renal histological alterations induced by gentamicin in rats. Saudi J Biol Sci. 2012;19:103–110.
24. Hajihashemi S , Jafarian T , Ahmadi M , Rahbari A , Ghanbari F . Ameliorative Effects of Zataria Multiflora Hydro-Alcoholic extract on Gentamicin InducedNephrotoxicity in Rats. Drug Res (Stuttg). 2018;68(7):387-394.
25. Luo QH , Chen ML, Sun FJ, Chen ZL, Li MY, Zeng W, et al. KIM-1 and NGAL as biomarkers of nephrotoxicity induced by gentamicin in rats. Mol Cell Biochem. 2014;397(1-2):53-60.
26. C. C. Szeto, B. C. H. Kwan, K. B. Lai et al. Urinary expression of kidney injury markers in renal transplant recipients, Clinical Journal of the American Society of Nephrology, vol. 5, no. 12, pp. 2329–2337, 2010.
27. K. Makris, N. Markou, E. Evodia et al., “Urinary neutrophil gelatinase-associated lipocalin (NGAL) as an early marker of
acute kidney injury in critically ill multiple trauma patients,†Clinical Chemistry and LaboratoryMedicine, vol. 47,no. 1, pp. 79–82, 2009.
28. Geus H. R. H. Bakker de.Neutrophil gelatinase-associated lipocalin at ICU admission predicts for acute kidney injury in adult patients,†American Journal of Respiratory and Critical Care Medicine, vol. 183, no. 7, pp. 907–914, 2011.
29. Kader C , Sunbul M , Das YK , Yarim M , Bedir A , Karaca E , et al Telbivudine attenuates gentamicin-induced kidney injury in rats. Int J Antimicrob Agents. 2017 ;49(5):595-602.
30. Al Suleimani YM , Abdelrahman AM , Karaca T , Manoj P , Ashique M , Nemmar A , et al. The effect of the dipeptidyl peptidase-4 inhibitor sitagliptin on gentamicin nephrotoxicity in mice.Biomed Pharmacother. 2018;97:1102-1108.
31. Alimoradian A , Changizi-Ashtiyani S, Ghiasabadi Farahani A, Kheder L, Rajabi R, Sharifi A. Protective Effects of Pomegranate Juice on Nephrotoxicity Induced by Captopril and Gentamicinin Rats. Iran J Kidney Dis. 2017;11(6):422-429.
32. Primarizky H , Yuniarti WM , Lukiswanto BS . Benefits of pomegranate (Punica granatum Linn) fruit extracts to weight changes, total protein, and uric acid in white rats (Rattus norvegicus) as an animal model of acute renal failure. Send to Vet World. 2016 ;9(11):1269-1274.
33. Boroushaki MT , Asadpour E , Sadeghnia HR , Dolati K . Effect of pomegranate seed oil against gentamicin -induced nephrotoxicity in rat. J Food Sci Technol. 2014;51(11):3510-4.
34. Cekmen M , Otunctemur A, Ozbek E, Cakir SS, Dursun M, Polat EC, et al. Pomegranate extract attenuates gentamicin-induced nephrotoxicity in rats by reducing oxidative stress. Ren Fail. 2013; 35(2):268-74.
35. El-Arabey AA . Negative Response of Phytoestrogens of Pomegranate Flower Extract against Cisplatin-induced Nephrotoxicity in Female Rats. Int J Prev Med. 2016 Jun 27;7:89.
36. Motamedi F , Nematbakhsh M , Monajemi R , Pezeshki Z , Talebi A , Zolfaghari B , et al. Effect of pomegranate flower extract on cisplatin-induced nephrotoxicity in rats. J Nephropathol. 2014;3(4):133-8.
37. Nematbakhsh M , Ebrahimian S, Tooyserkani M, Eshraghi-Jazi F, Talebi A, Ashrafi F. Gender difference in Cisplatin-induced nephrotoxicity in a rat model: greater intensity of damage in male than female. Nephrourol Mon. 2013;5(3):818-21.
38. Boroushaki MT , Asadpour E , Sadeghnia HR , Dolati K . Effect of pomegranate seed oil against gentamicin -induced nephrotoxicity in rat. J Food Sci Technol. 2014 ;51(11):3510-4.
39. Cekmen M , Otunctemur A, Ozbek E, Cakir SS, Dursun M, Polat EC, et al. Pomegranate extract attenuates gentamicin-induced nephrotoxicity in rats by reducing oxidative stress. Ren Fail. 2013;35(2):268-74.
40. Zhang L, Yang X, Zhang Y, Wang L, Zhang R. In vitro antioxidant properties of different parts of pomegranate flowers. Food Bioprod Process. 2011;89:234–40.
41. Jang A, Srinivasan P, Lee NY, Song HP, Lee JW, Lee M. et al. Comparison of hypolipidemic activity of synthetic gallic acid–linoleic acid ester with mixture of gallic acid and linoleic acid, gallic acid, and linoleic acid on high-fat diet induced obesity in C57BL/6 Cr Slc mice. Chem Biol Interact. 2008;174:109–17.
42. Azarkish F, Nematbakhsh M, Fazilati M, Talebi A, Pilehvarian AA, Pezeshki Z. et al. N-acetylcysteine Prevents Kidney and Lung Disturbances in Renal Ischemia/Reperfusion Injury in Rat. Int J Prev Med. 2013;4:1139.
43. Frutos P, Hervas G, Giraldez FJ, Mantecon AR. Frutos P, Hervas G, Giraldez FJ, Mantecon ARReviewTannins and ruminant nutrition. Span J Agric Res. 2004;2:191–202.
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Published
2019-02-26
How to Cite
Alkuraishy, H. M., Al-Gareeb, A. I., & Al-Naimi, M. S. (2019). Pomegranate protects renal proximal tubules during gentamicin induced-nephrotoxicity in rats. Journal of Contemporary Medical Sciences, 5(1), 35–40. https://doi.org/10.22317/jcms.v5i1.522
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