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Abstract
Background: Gentamicin can cause nephrotoxicity due to accumulation in proximal tubules then triggering free radicals generation that damage the nephrons. In response, our body produces endogenous antioxidants. However, extensive formation of free radicals requires exogenous antioxidants which can be obtained from herbal plants to compensate. Thus, rigorous preclinical and clinical studies are needed to prove the efficacy of medicinal plants that protect the kidneys from gentamicin nephrotoxicity.
Objective: This review article provides a scientific overview of the herbal plants’ nephroprotective activity towards gentamicin induction in vivo.
Method: A literature search through ScienceDirect database in July 2022 using the keywords “kidney damage”, “herbal plants”, and “gentamicin” resulted in 12 articles to be reviewed.
Results: We found 12 herbal plants proven to reverse the declining kidney function. We observed significant attenuation in elevated Blood Urea Nitrogen (BUN) and/or creatinine levels in subject animals receiving herbal plants compared to the gentamicin-induced group. This nephroprotective effect is due to the content of several compounds such as flavonoids, polyphenols, and tannins. Although each plant contains different compounds, all of them have antioxidant activity that inhibits oxidation in nephrons due to gentamicin induction.
Conclusion: The antioxidant compounds contained in herbal plants have the potential to prevent or treat nephrotoxicity due to gentamicin usage.
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References
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- Alimuddin, A., Murtini, S., Faridah, N., & Nuryati, S. (2019). Behavior, histopathology and physiological responses of rat fed diets containing growth hormone transgenic fish meal. HAYATI Journal of Biosciences, 26(1), 1–6. https://doi.org/https://doi.org/10.4308/hjb.26.1.1
- Balakumar, P., Rohilla, A., & Thangathirupathi, A. (2010). Gentamicin-induced nephrotoxicity: Do we have a promising therapeutic approach to blunt it? Pharmacol Res, 62(3), 179-186. https://doi.org/10.1016/j.phrs.2010.04.004
- Bastos-Cavalcante, N., Rodrigues dos Santos-Barbosa, C., Silva-Pereira, R. L., Feitosa-Muniz, D., de Melo-Coutinho, H. D., Araújo-Rolim, L., & da Silva- Almeida, J. R. G. (2020). Phytochemical Analysis, Antibacterial Activity and Antibiotic Modifying Action of Jatropha mollissima (Pohl.) Baill. (Euphorbiaceae). Anales de Biología(42), 85–94. https://doi.org/https://doi.org/10.6018/analesbio.42.10
- Chatterjee, P., Mukherjee, A., & Nandy, S. (2012). Protective effects of the aqueous leaf extract of Aloe barbadensis on gentamicin and cisplatin–induced nephrotoxic rats. Asian Pacific Journal of Tropical Biomedicine, 2(3, Supplement), S1754-S1763. https://doi.org/https://doi.org/10.1016/S2221-1691(12)60490-0
- Dar, N. J., Hamid, A., & Ahmad, M. (2015). Pharmacologic overview of Withania somnifera, the Indian Ginseng. Cell Mol Life Sci, 72(23), 4445-4460. https://doi.org/10.1007/s00018-015-2012-1
- Dewi, P. R. P., Hairrudin, H., & Normasari, R. (2016). Pengaruh Stres Fisik terhadap Kadar Kreatinin Serum Tikus Wistar Jantan (Rattus norvegicus). Pustaka Kesehatan, 4(2), 218–221. https://jurnal.unej.ac.id/index.php/JPK/article/view/3005
- Galdino, P. M., Alexandre, L. N. P., Lílian Fernanda Junior, Ruyde Souza Lino , Paula, J. R. P., Gustavo Rodrigues, & Xavier, C. H. F., Patrícia Maria (2017). Nephroprotective effect of Rudgea viburnoides (Cham.) Benth leaves on gentamicin-induced nephrotoxicity in rats. Journal of Ethnopharmacology, 201, 100-107. https://doi.org/https://doi.org/10.1016/j.jep.2017.02.035
- Ghaznavi, H., Fatemi, I., Kalantari, H., Hosseini Tabatabaei, S. M. T., Mehrabani, M., Gholamine, B., Kalantar, M., Mehrzadi, S., & Goudarzi, M. (2018). Ameliorative effects of gallic acid on gentamicin-induced nephrotoxicity in rats. J Asian Nat Prod Res, 20(12), 1182-1193. https://doi.org/10.1080/10286020.2017.1384819
- Ghédira, K., & Goetz, P. (2016). Malva sylvestris L. (Malvaceae) : Mauve. Phytothérapie, 14(1), 68-72. https://doi.org/10.1007/s10298-016-1023-x
- González-Coloma, A., López-Balboa, C., Santana, O., Reina, M., & Fraga, B. M. (2011). Triterpene-based plant defenses. Phytochemistry Reviews, 10(2), 245–260. https://doi.org/ https://doi.org/10.1007/s11101-010-9187-8
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- Gunawan, I. W. G., & Karda, I. M. (2015). Identifikasi Senyawa Minyak Atsiri dan Uji Aktivitas Antioksidan Ekstrak Etanol Kulit Batang Kepuh (Sterculia foetida L.). Chemistry Progress, 8(1), 12–16. https://doi.org/ https://doi.org/10.35799/cp.8.1.2015.9398
- Han, Z.-Z., Xu, H.-D., Kim, K.-H., Ahn, T.-H., Bae, J.-S., Lee, J.-Y., Gil, K.-H., Lee, J.-Y., Woo, S.-J., Yoo, H.-J., Lee, H.-K., Kim, K.-H., Park, C.-K., Zhang, H.-S., & Song, S.-W. (2010). Reference Data of the Main Physiological Parameters in Control Sprague-Dawley Rats from Pre-clinical Toxicity Studies. Laboratory Animal Research, 26, 153. https://doi.org/10.5625/lar.2010.26.2.153
- Hussain, T., Gupta, R. K., Sweety, K., Eswaran, B., Vijayakumar, M., & Rao, C. V. (2012). Nephroprotective activity of Solanum xanthocarpum fruit extract against gentamicin-induced nephrotoxicity and renal dysfunction in experimental rodents. Asian Pac J Trop Med, 5(9), 686-691. https://doi.org/10.1016/s1995-7645(12)60107-2
- Iqbal, M. O., & Yahya, E. B. (2021). In vivo assessment of reversing aminoglycoside antibiotics nephrotoxicity using Jatropha mollissima crude extract. Tissue Cell, 72, 101525. https://doi.org/10.1016/j.tice.2021.101525
- Irtawaty, A. (2017). Klasifikasi Penyakit Ginjal dengan Metode K-Means. JTT (Jurnal Teknologi Terpadu), 5, 49. https://doi.org/10.32487/jtt.v5i1.241
- Julianto, T. S. (2019). Fitokimia Tinjauan Metabolit Sekunder dan Skrining Fitokimia 1 ed., Yogyakarta, Indonesia: Universitas Islam Indonesia
- Kandeil, M. A. M., Hassanin, K. M. A., Mohammed, E. T., Safwat, G. M., & Mohamed, D. S. (2018). Wheat germ and vitamin E decrease BAX/BCL-2 ratio in rat kidney treated with gentamicin. Beni-Suef University Journal of Basic and Applied Sciences, 7(3), 257-262. https://doi.org/https://doi.org/10.1016/j.bjbas.2018.02.001
- Kardani, A. K., Soemyarso, N. A., Aras, J. A., Prasetyo, R. V., & Noer, M. S. (2021). Increased Interleukin-6 as Inflammatory Response and Magnesium Deficiency in Pre-dialysis Chronic Kidney Disease of Indonesian Children. Indonesian Journal of Tropical and Infectious Disease, 9(2), 93. https://doi.org/https://doi.org/10.20473/ijtid.v9i2.21479
- Kemenkes_RI. (2011). Pedoman Pelayanan Kefarmasian untuk Terapi Antibiotik Jakarta: Kementrian Kesehatan Republik Indonesia
- Kumar, S., & Pandey, A. K. (2013). Chemistry and Biological Activities of Flavonoids: An Overview. The Scientific World Journal, 2013, 162750. https://doi.org/10.1155/2013/162750
- Li, X.-L., Zhou, A.-G., Zhang, L., & Chen, W.-J. (2011). Antioxidant Status and Immune Activity of Glycyrrhizin in Allergic Rhinitis Mice. International Journal of Molecular Sciences, 12(2), 905-916. https://doi.org/https://doi.org/10.3390/ijms12020905
- Lintong, P. M., Kairupan, C. F., & Sondakh, P. L. N. (2013). Gambaran Mikroskopik Ginjal Tikus Wistar (Rattus norvegicus) Setelah Diinduksi Dengan Gentamisin. Jurnal Biomedik 4(3), 185–192. https://doi.org/ https://doi.org/10.35790/jbm.4.3.2012.800
- Lopez-Novoa, J. M., Quiros, Y., Vicente, L., Morales, A. I., & Lopez-Hernandez, F. J. (2011). New insights into the mechanism of aminoglycoside nephrotoxicity: an integrative point of view. Kidney Int, 79(1), 33-45. https://doi.org/10.1038/ki.2010.337
- Mohamadi Yarijani, Z., Najafi, H., Shackebaei, D., Madani, S. H., Modarresi, M., & Jassemi, S. V. (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. https://doi.org/10.1016/j.biopha.2019.108635
- Özkan, Ö., & Pekkaya, S. . (2019). Normal Values of Biochemical Parameters in Serum of New Zealand White Rabbits. Turk Hijyen ve Deneysel Biyoloji Dergisi, 76(2), 157–162. https://doi.org/https://doi.org/10.5505/TurkHijyen.2018.53254
- Priska, M., Peni, N., Carvallo, L., & Ngapa, Y. D. (2018). Review : Antosianin dan Pemanfaatannya. Cakra Kimia (Indonesian E-Journal of Applied Chemistry), 6(2), 79–97.
- Rashid, U., & Khan, M. R. (2017). Fagonia olivieri prevented hepatorenal injuries induced with gentamicin in rat. Biomed Pharmacother, 88, 469-479. https://doi.org/10.1016/j.biopha.2017.01.088
- Salih, N. A. (2015). Effect of nettle (Urtica dioica) extract on gentamicin induced nephrotoxicity in male rabbits. Asian Pacific Journal of Tropical Biomedicine, 5(9), 756-760. https://doi.org/https://doi.org/10.1016/j.apjtb.2015.07.005
- Siahaan, G., Lintong, P., & Loho, L. (2016). Gambaran histopatologik ginjal tikus wistar (Rattus norvegicus) yang diinduksi gentamisin dan diberikan ubi jalar ungu (Ipomoea batatas L. Poir). Jurnal e-Biomedik, 4(1). https://doi.org/10.35790/ebm.4.1.2016.12229
- Silverman, J. (2012). Biomedical Research Techniques. In In The Laboratory Rabbit, Guinea Pig, Hamster, and Other Rodents (1 ed.). Elsevier Inc. https://doi.org/ https://doi.org/10.1016/B978-0-12-380920-9.00029-8
- Sujono, T. A., & Rizki, F. A. (2020). Efek Nefroprotektif Ekstrak Etanol Bawang Putih (Allium sativum L.) pada Tikus yang Diinduksi Gentamisin. Pharmacon Jurnal Farmasi Indonesia, 1–9.
- Ungurianu, A., Zanfirescu, A., Nițulescu, G., & Margină, D. (2021). Vitamin E beyond Its Antioxidant Label. Antioxidants (Basel), 10(5). https://doi.org/10.3390/antiox10050634
- Veljković, M., Pavlović, D. R., Stojiljković, N., Ilić, S., Petrović, A., Jovanović, I., & Radenković, M. (2016). Morphological and morphometric study of protective effect of green tea in gentamicin-induced nephrotoxicity in rats. Life Sci, 147, 85-91. https://doi.org/10.1016/j.lfs.2016.01.035
- Vysakh, A., Abhilash, S., Kuriakose, J., Midhun, S. J., Jyothis, M., & Latha, M. S. (2018). Protective effect of Rotula aquatica Lour against gentamicin induced oxidative stress and nephrotoxicity in Wistar rats. Biomedicine & Pharmacotherapy, 106, 1188-1194. https://doi.org/https://doi.org/10.1016/j.biopha.2018.07.066
References
Aksoy, N., Dogan, Y., Iriadam, M., Bitiren, M., Uzer, E., Ozgonul, A., & Aksoy, S. (2012). Protective and therapeutic effects of licorice in rats with acute tubular necrosis. J Ren Nutr, 22(3), 336-343. https://doi.org/10.1053/j.jrn.2011.07.002
Alfonso, A. A., Mongan, A. E., & Memah, M. F. (2016). Gambaran kadar kreatinin serum pada pasien penyakit ginjal kronik stadium 5 non dialisis. Jurnal E-Biomedik, 4(2). https://doi.org/https://doi.org/10.35790/ebm.4.2.2016.12658
Alimuddin, A., Murtini, S., Faridah, N., & Nuryati, S. (2019). Behavior, histopathology and physiological responses of rat fed diets containing growth hormone transgenic fish meal. HAYATI Journal of Biosciences, 26(1), 1–6. https://doi.org/https://doi.org/10.4308/hjb.26.1.1
Balakumar, P., Rohilla, A., & Thangathirupathi, A. (2010). Gentamicin-induced nephrotoxicity: Do we have a promising therapeutic approach to blunt it? Pharmacol Res, 62(3), 179-186. https://doi.org/10.1016/j.phrs.2010.04.004
Bastos-Cavalcante, N., Rodrigues dos Santos-Barbosa, C., Silva-Pereira, R. L., Feitosa-Muniz, D., de Melo-Coutinho, H. D., Araújo-Rolim, L., & da Silva- Almeida, J. R. G. (2020). Phytochemical Analysis, Antibacterial Activity and Antibiotic Modifying Action of Jatropha mollissima (Pohl.) Baill. (Euphorbiaceae). Anales de Biología(42), 85–94. https://doi.org/https://doi.org/10.6018/analesbio.42.10
Chatterjee, P., Mukherjee, A., & Nandy, S. (2012). Protective effects of the aqueous leaf extract of Aloe barbadensis on gentamicin and cisplatin–induced nephrotoxic rats. Asian Pacific Journal of Tropical Biomedicine, 2(3, Supplement), S1754-S1763. https://doi.org/https://doi.org/10.1016/S2221-1691(12)60490-0
Dar, N. J., Hamid, A., & Ahmad, M. (2015). Pharmacologic overview of Withania somnifera, the Indian Ginseng. Cell Mol Life Sci, 72(23), 4445-4460. https://doi.org/10.1007/s00018-015-2012-1
Dewi, P. R. P., Hairrudin, H., & Normasari, R. (2016). Pengaruh Stres Fisik terhadap Kadar Kreatinin Serum Tikus Wistar Jantan (Rattus norvegicus). Pustaka Kesehatan, 4(2), 218–221. https://jurnal.unej.ac.id/index.php/JPK/article/view/3005
Galdino, P. M., Alexandre, L. N. P., Lílian Fernanda Junior, Ruyde Souza Lino , Paula, J. R. P., Gustavo Rodrigues, & Xavier, C. H. F., Patrícia Maria (2017). Nephroprotective effect of Rudgea viburnoides (Cham.) Benth leaves on gentamicin-induced nephrotoxicity in rats. Journal of Ethnopharmacology, 201, 100-107. https://doi.org/https://doi.org/10.1016/j.jep.2017.02.035
Ghaznavi, H., Fatemi, I., Kalantari, H., Hosseini Tabatabaei, S. M. T., Mehrabani, M., Gholamine, B., Kalantar, M., Mehrzadi, S., & Goudarzi, M. (2018). Ameliorative effects of gallic acid on gentamicin-induced nephrotoxicity in rats. J Asian Nat Prod Res, 20(12), 1182-1193. https://doi.org/10.1080/10286020.2017.1384819
Ghédira, K., & Goetz, P. (2016). Malva sylvestris L. (Malvaceae) : Mauve. Phytothérapie, 14(1), 68-72. https://doi.org/10.1007/s10298-016-1023-x
González-Coloma, A., López-Balboa, C., Santana, O., Reina, M., & Fraga, B. M. (2011). Triterpene-based plant defenses. Phytochemistry Reviews, 10(2), 245–260. https://doi.org/ https://doi.org/10.1007/s11101-010-9187-8
Govindappa, P. K., Gautam, V., Tripathi, S. M., Sahni, Y. P., & Raghavendra, H. L. S. (2019). Effect of Withania somnifera on gentamicin induced renal lesions in rats. Revista Brasileira de Farmacognosia, 29(2), 234-240. https://doi.org/https://doi.org/10.1016/j.bjp.2018.12.005
Gunawan, I. W. G., & Karda, I. M. (2015). Identifikasi Senyawa Minyak Atsiri dan Uji Aktivitas Antioksidan Ekstrak Etanol Kulit Batang Kepuh (Sterculia foetida L.). Chemistry Progress, 8(1), 12–16. https://doi.org/ https://doi.org/10.35799/cp.8.1.2015.9398
Han, Z.-Z., Xu, H.-D., Kim, K.-H., Ahn, T.-H., Bae, J.-S., Lee, J.-Y., Gil, K.-H., Lee, J.-Y., Woo, S.-J., Yoo, H.-J., Lee, H.-K., Kim, K.-H., Park, C.-K., Zhang, H.-S., & Song, S.-W. (2010). Reference Data of the Main Physiological Parameters in Control Sprague-Dawley Rats from Pre-clinical Toxicity Studies. Laboratory Animal Research, 26, 153. https://doi.org/10.5625/lar.2010.26.2.153
Hussain, T., Gupta, R. K., Sweety, K., Eswaran, B., Vijayakumar, M., & Rao, C. V. (2012). Nephroprotective activity of Solanum xanthocarpum fruit extract against gentamicin-induced nephrotoxicity and renal dysfunction in experimental rodents. Asian Pac J Trop Med, 5(9), 686-691. https://doi.org/10.1016/s1995-7645(12)60107-2
Iqbal, M. O., & Yahya, E. B. (2021). In vivo assessment of reversing aminoglycoside antibiotics nephrotoxicity using Jatropha mollissima crude extract. Tissue Cell, 72, 101525. https://doi.org/10.1016/j.tice.2021.101525
Irtawaty, A. (2017). Klasifikasi Penyakit Ginjal dengan Metode K-Means. JTT (Jurnal Teknologi Terpadu), 5, 49. https://doi.org/10.32487/jtt.v5i1.241
Julianto, T. S. (2019). Fitokimia Tinjauan Metabolit Sekunder dan Skrining Fitokimia 1 ed., Yogyakarta, Indonesia: Universitas Islam Indonesia
Kandeil, M. A. M., Hassanin, K. M. A., Mohammed, E. T., Safwat, G. M., & Mohamed, D. S. (2018). Wheat germ and vitamin E decrease BAX/BCL-2 ratio in rat kidney treated with gentamicin. Beni-Suef University Journal of Basic and Applied Sciences, 7(3), 257-262. https://doi.org/https://doi.org/10.1016/j.bjbas.2018.02.001
Kardani, A. K., Soemyarso, N. A., Aras, J. A., Prasetyo, R. V., & Noer, M. S. (2021). Increased Interleukin-6 as Inflammatory Response and Magnesium Deficiency in Pre-dialysis Chronic Kidney Disease of Indonesian Children. Indonesian Journal of Tropical and Infectious Disease, 9(2), 93. https://doi.org/https://doi.org/10.20473/ijtid.v9i2.21479
Kemenkes_RI. (2011). Pedoman Pelayanan Kefarmasian untuk Terapi Antibiotik Jakarta: Kementrian Kesehatan Republik Indonesia
Kumar, S., & Pandey, A. K. (2013). Chemistry and Biological Activities of Flavonoids: An Overview. The Scientific World Journal, 2013, 162750. https://doi.org/10.1155/2013/162750
Li, X.-L., Zhou, A.-G., Zhang, L., & Chen, W.-J. (2011). Antioxidant Status and Immune Activity of Glycyrrhizin in Allergic Rhinitis Mice. International Journal of Molecular Sciences, 12(2), 905-916. https://doi.org/https://doi.org/10.3390/ijms12020905
Lintong, P. M., Kairupan, C. F., & Sondakh, P. L. N. (2013). Gambaran Mikroskopik Ginjal Tikus Wistar (Rattus norvegicus) Setelah Diinduksi Dengan Gentamisin. Jurnal Biomedik 4(3), 185–192. https://doi.org/ https://doi.org/10.35790/jbm.4.3.2012.800
Lopez-Novoa, J. M., Quiros, Y., Vicente, L., Morales, A. I., & Lopez-Hernandez, F. J. (2011). New insights into the mechanism of aminoglycoside nephrotoxicity: an integrative point of view. Kidney Int, 79(1), 33-45. https://doi.org/10.1038/ki.2010.337
Mohamadi Yarijani, Z., Najafi, H., Shackebaei, D., Madani, S. H., Modarresi, M., & Jassemi, S. V. (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. https://doi.org/10.1016/j.biopha.2019.108635
Özkan, Ö., & Pekkaya, S. . (2019). Normal Values of Biochemical Parameters in Serum of New Zealand White Rabbits. Turk Hijyen ve Deneysel Biyoloji Dergisi, 76(2), 157–162. https://doi.org/https://doi.org/10.5505/TurkHijyen.2018.53254
Priska, M., Peni, N., Carvallo, L., & Ngapa, Y. D. (2018). Review : Antosianin dan Pemanfaatannya. Cakra Kimia (Indonesian E-Journal of Applied Chemistry), 6(2), 79–97.
Rashid, U., & Khan, M. R. (2017). Fagonia olivieri prevented hepatorenal injuries induced with gentamicin in rat. Biomed Pharmacother, 88, 469-479. https://doi.org/10.1016/j.biopha.2017.01.088
Salih, N. A. (2015). Effect of nettle (Urtica dioica) extract on gentamicin induced nephrotoxicity in male rabbits. Asian Pacific Journal of Tropical Biomedicine, 5(9), 756-760. https://doi.org/https://doi.org/10.1016/j.apjtb.2015.07.005
Siahaan, G., Lintong, P., & Loho, L. (2016). Gambaran histopatologik ginjal tikus wistar (Rattus norvegicus) yang diinduksi gentamisin dan diberikan ubi jalar ungu (Ipomoea batatas L. Poir). Jurnal e-Biomedik, 4(1). https://doi.org/10.35790/ebm.4.1.2016.12229
Silverman, J. (2012). Biomedical Research Techniques. In In The Laboratory Rabbit, Guinea Pig, Hamster, and Other Rodents (1 ed.). Elsevier Inc. https://doi.org/ https://doi.org/10.1016/B978-0-12-380920-9.00029-8
Sujono, T. A., & Rizki, F. A. (2020). Efek Nefroprotektif Ekstrak Etanol Bawang Putih (Allium sativum L.) pada Tikus yang Diinduksi Gentamisin. Pharmacon Jurnal Farmasi Indonesia, 1–9.
Ungurianu, A., Zanfirescu, A., Nițulescu, G., & Margină, D. (2021). Vitamin E beyond Its Antioxidant Label. Antioxidants (Basel), 10(5). https://doi.org/10.3390/antiox10050634
Veljković, M., Pavlović, D. R., Stojiljković, N., Ilić, S., Petrović, A., Jovanović, I., & Radenković, M. (2016). Morphological and morphometric study of protective effect of green tea in gentamicin-induced nephrotoxicity in rats. Life Sci, 147, 85-91. https://doi.org/10.1016/j.lfs.2016.01.035
Vysakh, A., Abhilash, S., Kuriakose, J., Midhun, S. J., Jyothis, M., & Latha, M. S. (2018). Protective effect of Rotula aquatica Lour against gentamicin induced oxidative stress and nephrotoxicity in Wistar rats. Biomedicine & Pharmacotherapy, 106, 1188-1194. https://doi.org/https://doi.org/10.1016/j.biopha.2018.07.066