Nephroprotective Effect of Ethanol Extract Abelmoschus manihot l. Leaves in Gentamicin-Induced Mice
Keywords:
Abelmoschus manihot L., gentamicin, nephroprotection, renal histopathology
Abstract
Nephrotoxicity is the most common side effect of gentamicin, an aminoglycoside antibiotic group. It was mediated by oxidative stress mechanisms. Abelmoschus manihot L. leaves (AML) have antioxidant activity flavonoids. This study aims to determine the nephroprotective effect of AML in gentamicin-induced nephrotoxicity using mice models. It conducted an experimental design study in a pharmacology laboratory using mice models. It was conducted experimentally in 7 groups. There are normal, solvent, negative control, and four test groups (given an ethanolic extract of AML at doses of 50, 100, 200, and 400 mg/kgBW) which were administered orally for 7 days. Gentamicin 112 mg/kgBW was induced intraperitoneally on the 8th day. All mice were anesthetized on the 11th day to collect blood serum and renal organs for further examination. The data were analyzed using SPSS version 26 for One Way ANOVA test and followed by Duncan's post-hoc analysis test. The difference is considered significant if the p-value <0.05. Gentamicin successfully induced renal damage based on increasing creatinine and blood urea nitrogen (BUN) levels. This was by histopathology analysis which showed renal necrosis in the negative control group. Ethanolic extract of AML prevents nephrotoxicity due to gentamicin in a dose-dependent manner in creatinine level but not in BUN and histopathology. However, taken together all results showed that ethanol extract of AML has a nephroprotective effect in gentamicin-induced nephrotoxicity.
Keywords: Abelmoschus manihot L., gentamicin, nephroprotection, renal histopathology
References
Ali, A. et al. (2022). Nephroprotective effects of Helianthus annuus seeds extract in gentamicin induced nephrotoxic male mice. Cellular and Molecular Biology, 68(1), pp. 1–7.
http://dx.doi.org/10.14715/cmb/2022.68.1.1
Amang, A. P. et al. (2020). Effects of aqueous extract of root barks of Swartzia madagascariensis (Caesalpiniaceae) on acute kidney failure induced with gentamicin in Wistar rats. Journal of Medicinal Plants Studies, 8(4), pp. 183–197.
http://www.plantsjournal.com
Amarasiri, S. S. et al. (2020). Acute and 28-day repeated-dose oral toxicity assessment of Abelmoschus moschatus Medik. in healthy Wistar rats. Evidence-Based Complementary and Alternative Medicine, 2020.
https://doi.org/10.1155/2020/1359050
Chatterjee, P., Mukherjee, A. and 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), pp. S1754--S1763.
https://doi.org/10.1016/S2221-1691(12)60490-0
Dahal, A. and Mulukuri, S. (2015). Flavonoids in kidney protection. World J. Pharm. Pharmaceut. Sci, 4(3), pp. 362–382.
Edeogu, C. O. et al. (2020). Nephroprotective effect of Moringa oleifera seed oil on gentamicin-induced nephrotoxicity in rats: biochemical evaluation of antioxidant, anti-inflammatory, and antiapoptotic pathways. Journal of the American college of nutrition, 39(4), pp. 307–315.
https://doi.org/10.1080/07315724.2019.1649218
Govindappa, P. K. et al. (2019). Effect of Withania somnifera on gentamicin induced renal lesions in rats. Revista Brasileira de Farmacognosia, 29(2), pp. 234–240.
https://doi.org/10.1016/j.bjp.2018.12.005
Hubert, D. and Simmonds, N. (2015). Living longer with cystic fibrosis. European Cystic Fibrosis Society, 390.
Josiah, S. S. et al. (2020). Renoprotective property of the flavonoid-rich extract of Kigelia africana fruits on gentamicin-induced nephrotoxicity in rats. Comparative Clinical Pathology, 29, pp. 815–828.
https://doi.org/10.1007/s00580-020-03140-w
Kim, S. Y. and Moon, A. (2012). Drug-induced nephrotoxicity and its biomarkers. Biomolecules \& therapeutics, 20(3), p. 268.
doi: 10.4062/biomolther.2012.20.3.268
Kwon, H. J. et al. (2022). Analysis of antioxidant activity, total phenol content, and flavonoid content of Abelmoschus manihot flower extracts. Korean Journal of Food Preservation, 29(1), pp. 157–165.
doi: https://doi.org/10.11002/kjfp.2022.29.1.157
Lopez-Novoa, J. M. et al. (2011). New insights into the mechanism of aminoglycoside nephrotoxicity: an integrative point of view. Kidney international, 79(1), pp. 33–45.
https://doi.org/10.1038/ki.2010.337
Ali, A. et al. (2022). Nephroprotective effects of Helianthus annuus seeds extract in gentamicin induced nephrotoxic male mice. Cellular and Molecular Biology, 68(1), pp. 1–7.
http://dx.doi.org/10.14715/cmb/2022.68.1.1
Amang, A. P. et al. (2020). Effects of aqueous extract of root barks of Swartzia madagascariensis (Caesalpiniaceae) on acute kidney failure induced with gentamicin in Wistar rats. Journal of Medicinal Plants Studies, 8(4), pp. 183–197.
http://www.plantsjournal.com
Amarasiri, S. S. et al. (2020). Acute and 28-day repeated-dose oral toxicity assessment of Abelmoschus moschatus Medik. in healthy Wistar rats. Evidence-Based Complementary and Alternative Medicine, 2020.
https://doi.org/10.1155/2020/1359050
Chatterjee, P., Mukherjee, A. and 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), pp. S1754--S1763.
https://doi.org/10.1016/S2221-1691(12)60490-0
Dahal, A. and Mulukuri, S. (2015). Flavonoids in kidney protection. World J. Pharm. Pharmaceut. Sci, 4(3), pp. 362–382.
Edeogu, C. O. et al. (2020). Nephroprotective effect of Moringa oleifera seed oil on gentamicin-induced nephrotoxicity in rats: biochemical evaluation of antioxidant, anti-inflammatory, and antiapoptotic pathways. Journal of the American college of nutrition, 39(4), pp. 307–315.
https://doi.org/10.1080/07315724.2019.1649218
Govindappa, P. K. et al. (2019). Effect of Withania somnifera on gentamicin induced renal lesions in rats. Revista Brasileira de Farmacognosia, 29(2), pp. 234–240.
https://doi.org/10.1016/j.bjp.2018.12.005
Hubert, D. and Simmonds, N. (2015). Living longer with cystic fibrosis. European Cystic Fibrosis Society, 390.
Josiah, S. S. et al. (2020). Renoprotective property of the flavonoid-rich extract of Kigelia africana fruits on gentamicin-induced nephrotoxicity in rats. Comparative Clinical Pathology, 29, pp. 815–828.
https://doi.org/10.1007/s00580-020-03140-w
Kim, S. Y. and Moon, A. (2012). Drug-induced nephrotoxicity and its biomarkers. Biomolecules \& therapeutics, 20(3), p. 268.
doi: 10.4062/biomolther.2012.20.3.268
Kwon, H. J. et al. (2022). Analysis of antioxidant activity, total phenol content, and flavonoid content of Abelmoschus manihot flower extracts. Korean Journal of Food Preservation, 29(1), pp. 157–165.
doi: https://doi.org/10.11002/kjfp.2022.29.1.157
Lopez-Novoa, J. M. et al. (2011). New insights into the mechanism of aminoglycoside nephrotoxicity: an integrative point of view. Kidney international, 79(1), pp. 33–45.
https://doi.org/10.1038/ki.2010.337
Luan, F. et al. (2020). Traditional uses, chemical constituents, biological properties, clinical settings, and toxicities of Abelmoschus manihot L.: a comprehensive review. Frontiers in pharmacology, 11, p. 1068.
https://doi.org/10.3389/fphar.2020.01068
Magno, A. L., Ward, B. K. and Ratajczak, T. (2011). The calcium-sensing receptor: a molecular perspective. Endocrine reviews, 32(1), pp. 3–30.
https://doi.org/10.1210/er.2009-0043
Mandey, J. S. et al. (2014). Genetics characterization, nutritional and phytochemicals potential of gedi leaves (Abelmoschus manihot (L.) Medik) growing in the North Sulawesi of Indonesia as a candidate of poultry feed. Journal of Research in Biology, 4(2), pp. 1276–1286.
McLarnon, S. J. et al. (2002). Aminoglycoside antibiotics induce pH-sensitive activation of the calcium-sensing receptor. Biochemical and biophysical research communications, 297(1), pp. 71–77.
https://doi.org/10.1016/S0006-291X(02)02133-2
Meka Kedir, W., Dukassa Dubiwak, A. and Tofik Ahmed, E. (2022). Nephroprotective effect of asparagus africanus lam. root extract against gentamicin-induced nephrotoxicity in swiss albino mice. Journal of Toxicology, 2022.
https://doi.org/10.1155/2022/8440019
Miller, M. A. and Zachary, J. F. (2017). Mechanisms and morphology of cellular injury, adaptation, and death. Pathologic basis of veterinary disease, p. 2.
doi: 10.1016/B978-0-323-35775-3.00001-1
Mitchell, R. N. and Cotran, R. S. (2007). Cell injury, cell death, and adaptations. Basic Pathology (8th ed.). Kumar V, Cotran R, Robbins SL (Eds). Elsevier Science, Philadelphia, pp. 19–22.
Mitruka, B. M., Rawnsley, H. M. and others (1977) Clinical biochemical and hematological reference values in normal experimental animals. Masson Publishing USA Inc.
Otunctemur, A. et al. (2013). Protective effect of montelukast which is cysteinyl-leukotriene receptor antagonist on gentamicin-induced nephrotoxicity and oxidative damage in rat kidney. Renal failure, 35(3), pp. 403–410.
https://doi.org/10.3109/0886022X.2012.761040
Padmalochana, K. and Dhana Rajan, K. S. (2015). In vivo nephroprotective potential from leaves extracts of Andrographis paniculata. World Journal of Pharmacy and Pharmaceutical Sciences, 4, pp. 1416–1425.
Randjelovic, P. et al. (2017). Gentamicin nephrotoxicity in animals: Current knowledge and future perspectives. EXCLI journal, 16, p. 388.
doi: 10.17179/excli2017-165
Sahu, B. D. et al. (2014). Naringin ameliorates gentamicin-induced nephrotoxicity and associated mitochondrial dysfunction, apoptosis and inflammation in rats: possible mechanism of nephroprotection. Toxicology and applied pharmacology, 277(1), pp. 8–20.
https://doi.org/10.1016/j.taap.2014.02.022
Sari, D. C. R. et al. (2021). Centella asiatica extract attenuates kidney fibrosis through reducing mesenchymal transition and inflammation in ureteral ligation model in mice. Frontiers in Pharmacology, 12, p. 621894.
https://doi.org/10.3389/fphar.2021.621894
Sarwar, S. et al. (2022). Renoprotection of selected antioxidant-rich foods (water spinach and red grape) and probiotics in gentamicin-induced nephrotoxicity and oxidative stress in rats. Life, 12(1), p. 60.
https://doi.org/10.3390/life12010060
Suliska, N. et al. (2021). Nephroprotective effect of ethanol extract of Sonchus arvensis L. leaves in gentamicin-piroxicam induced rat renal failure. Journal of Research in Pharmacy, 25(4).
doi: 10.29228/jrp.35
Taroreh, M. et al. (2016). Antioxidative activities of various fractions of gedi’s leaf extracts (Abelmoschus manihot L. medik). Agriculture and Agricultural Science Procedia, 9, pp. 271–278.
https://doi.org/10.1016/j.aaspro.2016.02.112
Tavafi, M., Ahmadvand, H. and Toolabi, P. (2012). Inhibitory effect of olive leaf extract on gentamicin-induced nephrotoxicity in rats.
Todarwal, A., Jain, P. and Bari, S. (2011). Abelmoschus manihot Linn: ethnobotany, phytochemistry and pharmacology. Asian Journal of Traditional Medicines, 6(1), pp. 1–7.
Wang, R. et al. (2019). Citrus aurantium ameliorates cisplatin-induced nephrotoxicity. BioMed research international, 2019.
https://doi.org/10.1155/2019/3960908
Sodimbaku, V., Pujari, L., Mullangi, R. and Marri, S., (2016). Carrot (Daucus carota L.): Nephroprotective against gentamicin-induced nephrotoxicity in rats. Indian Journal of Pharmacology, 48(2), p.122.
doi: 10.4103/0253-7613.178822
Zulfi, Z., Ilyas, S. and Hutahaean, S. (2013). Pengaruh pemberian vitamin C dan E terhadap gambaran histologis ginjal mencit (Mus musculus L.) yang dipajankan monosodium glutamat (MSG). Saintia Biologi, 1(3), pp. 1–6.
https://doi.org/10.35963/midwifery.v4i1.121
http://dx.doi.org/10.14715/cmb/2022.68.1.1
Amang, A. P. et al. (2020). Effects of aqueous extract of root barks of Swartzia madagascariensis (Caesalpiniaceae) on acute kidney failure induced with gentamicin in Wistar rats. Journal of Medicinal Plants Studies, 8(4), pp. 183–197.
http://www.plantsjournal.com
Amarasiri, S. S. et al. (2020). Acute and 28-day repeated-dose oral toxicity assessment of Abelmoschus moschatus Medik. in healthy Wistar rats. Evidence-Based Complementary and Alternative Medicine, 2020.
https://doi.org/10.1155/2020/1359050
Chatterjee, P., Mukherjee, A. and 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), pp. S1754--S1763.
https://doi.org/10.1016/S2221-1691(12)60490-0
Dahal, A. and Mulukuri, S. (2015). Flavonoids in kidney protection. World J. Pharm. Pharmaceut. Sci, 4(3), pp. 362–382.
Edeogu, C. O. et al. (2020). Nephroprotective effect of Moringa oleifera seed oil on gentamicin-induced nephrotoxicity in rats: biochemical evaluation of antioxidant, anti-inflammatory, and antiapoptotic pathways. Journal of the American college of nutrition, 39(4), pp. 307–315.
https://doi.org/10.1080/07315724.2019.1649218
Govindappa, P. K. et al. (2019). Effect of Withania somnifera on gentamicin induced renal lesions in rats. Revista Brasileira de Farmacognosia, 29(2), pp. 234–240.
https://doi.org/10.1016/j.bjp.2018.12.005
Hubert, D. and Simmonds, N. (2015). Living longer with cystic fibrosis. European Cystic Fibrosis Society, 390.
Josiah, S. S. et al. (2020). Renoprotective property of the flavonoid-rich extract of Kigelia africana fruits on gentamicin-induced nephrotoxicity in rats. Comparative Clinical Pathology, 29, pp. 815–828.
https://doi.org/10.1007/s00580-020-03140-w
Kim, S. Y. and Moon, A. (2012). Drug-induced nephrotoxicity and its biomarkers. Biomolecules \& therapeutics, 20(3), p. 268.
doi: 10.4062/biomolther.2012.20.3.268
Kwon, H. J. et al. (2022). Analysis of antioxidant activity, total phenol content, and flavonoid content of Abelmoschus manihot flower extracts. Korean Journal of Food Preservation, 29(1), pp. 157–165.
doi: https://doi.org/10.11002/kjfp.2022.29.1.157
Lopez-Novoa, J. M. et al. (2011). New insights into the mechanism of aminoglycoside nephrotoxicity: an integrative point of view. Kidney international, 79(1), pp. 33–45.
https://doi.org/10.1038/ki.2010.337
Ali, A. et al. (2022). Nephroprotective effects of Helianthus annuus seeds extract in gentamicin induced nephrotoxic male mice. Cellular and Molecular Biology, 68(1), pp. 1–7.
http://dx.doi.org/10.14715/cmb/2022.68.1.1
Amang, A. P. et al. (2020). Effects of aqueous extract of root barks of Swartzia madagascariensis (Caesalpiniaceae) on acute kidney failure induced with gentamicin in Wistar rats. Journal of Medicinal Plants Studies, 8(4), pp. 183–197.
http://www.plantsjournal.com
Amarasiri, S. S. et al. (2020). Acute and 28-day repeated-dose oral toxicity assessment of Abelmoschus moschatus Medik. in healthy Wistar rats. Evidence-Based Complementary and Alternative Medicine, 2020.
https://doi.org/10.1155/2020/1359050
Chatterjee, P., Mukherjee, A. and 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), pp. S1754--S1763.
https://doi.org/10.1016/S2221-1691(12)60490-0
Dahal, A. and Mulukuri, S. (2015). Flavonoids in kidney protection. World J. Pharm. Pharmaceut. Sci, 4(3), pp. 362–382.
Edeogu, C. O. et al. (2020). Nephroprotective effect of Moringa oleifera seed oil on gentamicin-induced nephrotoxicity in rats: biochemical evaluation of antioxidant, anti-inflammatory, and antiapoptotic pathways. Journal of the American college of nutrition, 39(4), pp. 307–315.
https://doi.org/10.1080/07315724.2019.1649218
Govindappa, P. K. et al. (2019). Effect of Withania somnifera on gentamicin induced renal lesions in rats. Revista Brasileira de Farmacognosia, 29(2), pp. 234–240.
https://doi.org/10.1016/j.bjp.2018.12.005
Hubert, D. and Simmonds, N. (2015). Living longer with cystic fibrosis. European Cystic Fibrosis Society, 390.
Josiah, S. S. et al. (2020). Renoprotective property of the flavonoid-rich extract of Kigelia africana fruits on gentamicin-induced nephrotoxicity in rats. Comparative Clinical Pathology, 29, pp. 815–828.
https://doi.org/10.1007/s00580-020-03140-w
Kim, S. Y. and Moon, A. (2012). Drug-induced nephrotoxicity and its biomarkers. Biomolecules \& therapeutics, 20(3), p. 268.
doi: 10.4062/biomolther.2012.20.3.268
Kwon, H. J. et al. (2022). Analysis of antioxidant activity, total phenol content, and flavonoid content of Abelmoschus manihot flower extracts. Korean Journal of Food Preservation, 29(1), pp. 157–165.
doi: https://doi.org/10.11002/kjfp.2022.29.1.157
Lopez-Novoa, J. M. et al. (2011). New insights into the mechanism of aminoglycoside nephrotoxicity: an integrative point of view. Kidney international, 79(1), pp. 33–45.
https://doi.org/10.1038/ki.2010.337
Luan, F. et al. (2020). Traditional uses, chemical constituents, biological properties, clinical settings, and toxicities of Abelmoschus manihot L.: a comprehensive review. Frontiers in pharmacology, 11, p. 1068.
https://doi.org/10.3389/fphar.2020.01068
Magno, A. L., Ward, B. K. and Ratajczak, T. (2011). The calcium-sensing receptor: a molecular perspective. Endocrine reviews, 32(1), pp. 3–30.
https://doi.org/10.1210/er.2009-0043
Mandey, J. S. et al. (2014). Genetics characterization, nutritional and phytochemicals potential of gedi leaves (Abelmoschus manihot (L.) Medik) growing in the North Sulawesi of Indonesia as a candidate of poultry feed. Journal of Research in Biology, 4(2), pp. 1276–1286.
McLarnon, S. J. et al. (2002). Aminoglycoside antibiotics induce pH-sensitive activation of the calcium-sensing receptor. Biochemical and biophysical research communications, 297(1), pp. 71–77.
https://doi.org/10.1016/S0006-291X(02)02133-2
Meka Kedir, W., Dukassa Dubiwak, A. and Tofik Ahmed, E. (2022). Nephroprotective effect of asparagus africanus lam. root extract against gentamicin-induced nephrotoxicity in swiss albino mice. Journal of Toxicology, 2022.
https://doi.org/10.1155/2022/8440019
Miller, M. A. and Zachary, J. F. (2017). Mechanisms and morphology of cellular injury, adaptation, and death. Pathologic basis of veterinary disease, p. 2.
doi: 10.1016/B978-0-323-35775-3.00001-1
Mitchell, R. N. and Cotran, R. S. (2007). Cell injury, cell death, and adaptations. Basic Pathology (8th ed.). Kumar V, Cotran R, Robbins SL (Eds). Elsevier Science, Philadelphia, pp. 19–22.
Mitruka, B. M., Rawnsley, H. M. and others (1977) Clinical biochemical and hematological reference values in normal experimental animals. Masson Publishing USA Inc.
Otunctemur, A. et al. (2013). Protective effect of montelukast which is cysteinyl-leukotriene receptor antagonist on gentamicin-induced nephrotoxicity and oxidative damage in rat kidney. Renal failure, 35(3), pp. 403–410.
https://doi.org/10.3109/0886022X.2012.761040
Padmalochana, K. and Dhana Rajan, K. S. (2015). In vivo nephroprotective potential from leaves extracts of Andrographis paniculata. World Journal of Pharmacy and Pharmaceutical Sciences, 4, pp. 1416–1425.
Randjelovic, P. et al. (2017). Gentamicin nephrotoxicity in animals: Current knowledge and future perspectives. EXCLI journal, 16, p. 388.
doi: 10.17179/excli2017-165
Sahu, B. D. et al. (2014). Naringin ameliorates gentamicin-induced nephrotoxicity and associated mitochondrial dysfunction, apoptosis and inflammation in rats: possible mechanism of nephroprotection. Toxicology and applied pharmacology, 277(1), pp. 8–20.
https://doi.org/10.1016/j.taap.2014.02.022
Sari, D. C. R. et al. (2021). Centella asiatica extract attenuates kidney fibrosis through reducing mesenchymal transition and inflammation in ureteral ligation model in mice. Frontiers in Pharmacology, 12, p. 621894.
https://doi.org/10.3389/fphar.2021.621894
Sarwar, S. et al. (2022). Renoprotection of selected antioxidant-rich foods (water spinach and red grape) and probiotics in gentamicin-induced nephrotoxicity and oxidative stress in rats. Life, 12(1), p. 60.
https://doi.org/10.3390/life12010060
Suliska, N. et al. (2021). Nephroprotective effect of ethanol extract of Sonchus arvensis L. leaves in gentamicin-piroxicam induced rat renal failure. Journal of Research in Pharmacy, 25(4).
doi: 10.29228/jrp.35
Taroreh, M. et al. (2016). Antioxidative activities of various fractions of gedi’s leaf extracts (Abelmoschus manihot L. medik). Agriculture and Agricultural Science Procedia, 9, pp. 271–278.
https://doi.org/10.1016/j.aaspro.2016.02.112
Tavafi, M., Ahmadvand, H. and Toolabi, P. (2012). Inhibitory effect of olive leaf extract on gentamicin-induced nephrotoxicity in rats.
Todarwal, A., Jain, P. and Bari, S. (2011). Abelmoschus manihot Linn: ethnobotany, phytochemistry and pharmacology. Asian Journal of Traditional Medicines, 6(1), pp. 1–7.
Wang, R. et al. (2019). Citrus aurantium ameliorates cisplatin-induced nephrotoxicity. BioMed research international, 2019.
https://doi.org/10.1155/2019/3960908
Sodimbaku, V., Pujari, L., Mullangi, R. and Marri, S., (2016). Carrot (Daucus carota L.): Nephroprotective against gentamicin-induced nephrotoxicity in rats. Indian Journal of Pharmacology, 48(2), p.122.
doi: 10.4103/0253-7613.178822
Zulfi, Z., Ilyas, S. and Hutahaean, S. (2013). Pengaruh pemberian vitamin C dan E terhadap gambaran histologis ginjal mencit (Mus musculus L.) yang dipajankan monosodium glutamat (MSG). Saintia Biologi, 1(3), pp. 1–6.
https://doi.org/10.35963/midwifery.v4i1.121
Published
2024-03-25
How to Cite
Dwi Sandhiutami, N. M., Nurefrialia Nisa, R., & Wardhani, B. W. K. (2024). Nephroprotective Effect of Ethanol Extract Abelmoschus manihot l. Leaves in Gentamicin-Induced Mice. Indonesian Journal of Pharmacy, 35(1), 83-92. https://doi.org/10.22146/ijp.8563
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Research Article
