Histopathological Changes of Renal Tubules in Metformin and A. Crassna Leaf Extract treated STZ-induced Diabetic Rats
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Published
Dec 28, 2022
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Abstract
This research is part of the project to study and assess the anti-diabetes effects of A. Crassna leaf extract treatment for STZ-induced diabetic rats, to evaluate tissue damage amelioration. To determine the side effects of Diabetes Mellitus (DM)-treated rats, metformin (a common anti-hyperglycemic medicine) and A. Crassna crude extract were tested on kidney tissue from the diabetic rats. We evaluated the changes in renal tubular histology in the kidneys of the diabetic rats that were given metformin and A. Crassna crude extract. Paraffin blocks with kidney samples embedded were prepared for each group: 1) control group, 2) diabetic group, 3) metformin-treated diabetes group, 4) A. Crassna leaf extract-treated diabetes group by 300 ml/kg (K300), and 5) 1000 ml/kg (K1000). The tissue sections were stained with routine hematoxylin and eosin and a special staining technique for glycogen accumulation identification, periodic acid-Schiff (PAS) reagent, to identify tubular pathology. In hyperglycemic conditions, as shown in the DM model in the metformin-treated group, and K300 and K1000 A. Crassna-treated investigations, subnuclear vacuolizations (Armanni-Ebstein lesions) were discovered to have increased by approximately 19.09% (p=0.01) in metformin-treated diabetic rats. However, tubular lesions were also observed in the DM, K300, and K1000 groups. The distal tubule is often targeted for tubular anomalies that do not damage the juxtaglomerular structure. The study demonstrates the renal tubular toxicity of metformin and A. Crassna leaf extract in acute hyperglycemic rats, possibly providing a renal side effect for diabetic treatment.
Keywords: A. Crassna, Diabetic nephropathy, Metformin, STZ-induced diabetic rats, PAS
References
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Dahham, S. S., Tabana, Y. M., Iqbal, M. A., Ahamed, M. B., Ezzat, M. O., Majid, A. S., & Majid, A. M. (2015). The Anticancer, Antioxidant and Antimicrobial Properties of the Sesquiterpene beta-Caryophyllene from the Essential Oil of Aquilaria crassna. Molecules, 20(7), 11808-11829. http://dx.doi.org/10.3390/molecules200711808
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Dineshkumar, B., Mitra, A., & Manjunatha, M. (2010). Studies on the anti-diabetic and hypolipidemic potentials of mangiferin (Xanthone Glucoside) in streptozotocin-induced Type 1 and Type 2 diabetic model rats. International Journal of Advances in Pharmaceutical Sciences, 1, 75-85. http://dx.doi.org/
10.5138/ijaps.2010.0976.1055.01009
Ebstein, W. (1882). Weiteres über Diabetes mellitus, insbesondere über die Complicationdesselben mit Typhus abdominalis. Deutsches Archiv für klinische Medizin, 30, 1-44.
Eppenga, W. L., Lalmohamed, A., Geerts, A. F., Derijks, H. J., Wensing, M., Egberts, A., . . . de Vries, F. (2014). Risk of lactic acidosis or elevated lactate concentrations in metformin users with renal impairment: a population-based cohort study. Diabetes Care, 37(8), 2218-2224. http://dx.doi.org/
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Ganogpichayagrai, A., Palanuvej, C., & Ruangrungsi, N. (2017). Antidiabetic and anticancer activities of Mangifera indica cv. Okrong leaves. Journal of Advanced Pharmaceutical Technology & Research, 8(1), 19-24. http://dx.doi.org/10.4103/2231-4040.197371
Hara, H., Ise, Y., Morimoto, N., Shimazawa, M., Ichihashi, K., Ohyama, M., & Iinuma, M. (2008). Laxative effect of agarwood leaves and its mechanism. Bioscience, Biotechnology, and Biochemistry, 72(2), 335-345. http://dx.doi.org/10.1271/bbb.70361
Hardie, D. G. (2008). Role of AMP-activated protein kinase in the metabolic syndrome and in heart disease. Federation of European Biochemical Societies Letters, 582(1), 81-89. http://dx.doi.org/10.1016/j.
febslet.2007.11.018
Hasanvand, A., Amini-Khoei, H., Hadian, M. R., Abdollahi, A., Tavangar, S. M., Dehpour, A. R., . . . Mehr, S. E. (2016). Anti-inflammatory effect of AMPK signaling pathway in rat model of diabetic neuropathy. Inflammopharmacology, 24(5), 207-219. http://dx.doi.org/10.1007/s10787-016-0275-2
Ichiki, H., Miura, T., Kubo, M., Ishihara, E., Komatsu, Y., Tanigawa, K., & Okada, M. (1998). New antidiabetic compounds, mangiferin and its glucoside. The Biological and Pharmaceutical Bulletin, 21(12), 1389-1390. http://dx.doi.org/10.1248/bpb.21.1389
Inzucchi, S. E., Bergenstal, R. M., Buse, J. B., Diamant, M., Ferrannini, E., Nauck, M., . . . European Association for the Study of, Diabetes. (2012). Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care, 35(6), 1364-1379. http://dx.
doi.org/10.2337/dc12-0413
Ishizaki, M., Masuda, Y., Fukuda, Y., Yamanaka, N., Masugi, Y., Shichinohe, K., & Nakama, K. (1987). Renal lesions in a strain of spontaneously diabetic WBN/Kob rats. Acta Diabetologica Latina, 24(1), 27-35. http://dx.doi.org/10.1007/BF02732050
Ito, Tetsuro, Kakino, Mamoru, Tazawa, Shigemi, Oyama, Masayoshi, Maruyama, Hiroe, Araki, Yoko, . . . Iinuma, Munekazu. (2012). Identification of Phenolic Compounds in Aquilaria crassna Leaves Via Liquid Chromatography-Electrospray Ionization Mass Spectroscopy. Food Science and Technology Research, 18(2), 259-262. http://dx.doi.org/10.3136/fstr.18.259
Kang, J., Dai, X. S., Yu, T. B., Wen, B., & Yang, Z. W. (2005). Glycogen accumulation in renal tubules, a key morphological change in the diabetic rat kidney. Acta Diabetologica, 42(2), 110-116. http://dx.doi.org/10.1007/s00592-005-0188-9
Kashihara, N., Haruna, Y., Kondeti, V. K., & Kanwar, Y. S. (2010). Oxidative stress in diabetic nephropathy. Current Medicinal Chemistry, 17(34), 4256-4269. http://dx.doi.org/10.2174/09298671079
3348581
Kawashima, I., & Kirito, K. (2016). Metformin inhibits JAK2V617F activity in MPN cells by activating AMPK and PP2A complexes containing the B56alpha subunit. Experimental Hematology, 44(12), 1156-1165 e1154. http://dx.doi.org/10.1016/j.exphem.2016.08.005
Kock, K. F., & Vestergaard, V. (1994). Armanni-Ebstein lesions of the kidney: diagnostic of death in diabetic coma? Forensic Science International, 67(3), 169-174. http://dx.doi.org/10.1016/0379-0738(94)90087-6
Nielsen, H., Thomsen, J. L., Kristensen, I. B., & Ottosen, P. D. (2003). Accumulation of triglycerides in the proximal tubule of the kidney in diabetic coma. Pathology, 35(4), 305-310. http://dx.doi.org/10.
1080/0031302031000150551
Pal, P. B., Sinha, K., & Sil, P. C. (2014). Mangiferin attenuates diabetic nephropathy by inhibiting oxidative stress mediated signaling cascade, TNFalpha related and mitochondrial dependent apoptotic pathways in streptozotocin-induced diabetic rats. PLoS One, 9(9), e107220. http://dx.doi.org/10.1371/
journal.pone.0107220
Pranakhon, R., Aromdee, C., & Pannangpetch, P. (2015). Effects of iriflophenone 3-C-beta-glucoside on fasting blood glucose level and glucose uptake. Pharmacognosy Magazine, 11(41), 82-89. http://dx.doi.org/10.4103/0973-1296.149711
Pranakhon, R., Pannangpetch, P., & Aromdee, C. (2011). Antihyperglycemic activity of agarwood leaf extracts in STZ-induced diabetic rats and glucose uptake enhancement activity in rat adipocytes. Songklanakarin Journal of Science and Technology, 33(4), 405-410.
Ray, G., Leelamanit, W., Sithisarn, P., & Jiratchariyakul, W. (2014). Antioxidative Compounds from Aquilaria crassna Leaf. Mahidol University Journal of Pharmaceutical Sciences, 41(4), 54-58.
Richy, F. F., Sabido-Espin, M., Guedes, S., Corvino, F. A., & Gottwald-Hostalek, U. (2014). Incidence of lactic acidosis in patients with type 2 diabetes with and without renal impairment treated with metformin: a retrospective cohort study. Diabetes Care, 37(8), 2291-2295. http://dx.doi.org/10.2337/dc14-0464
Ritchie, S., & Waugh, D. (1957). The pathology of Armanni-Ebstein diabetic nephropathy. The American Journal of Pathology, 33(6), 1035-1057.
Saravi, S. S. S., Hasanvand, A., Shahkarami, K., & Dehpour, A. R. (2016). The protective potential of metformin against acetaminophen-induced hepatotoxicity in BALB/C mice. Pharmaceutical Biology, 54(12), 2830-2837. http://dx.doi.org/10.1080/13880209.2016.1185633
Schwetz, V., Eisner, F., Schilcher, G., Eller, K., Plank, J., Lind, A., . . . Eller, P. (2017). Combined metformin-associated lactic acidosis and euglycemic ketoacidosis. Wien Klin Wochenschr, 129(17-18), 646-649. http://dx.doi.org/10.1007/s00508-017-1251-6
Soetikno, V., Watanabe, K., Sari, F. R., Harima, M., Thandavarayan, R. A., Veeraveedu, P. T., . . . Suzuki, K. (2011). Curcumin attenuates diabetic nephropathy by inhibiting PKC-alpha and PKC-beta1 activity in streptozotocin-induced type I diabetic rats. Molecular Nutrition & Food Research, 55(11), 1655-1665. http://dx.doi.org/10.1002/mnfr.201100080
Szkudelski, T. (2001). The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas. Physiological Research, 50(6), 537-546.
Tessari, P., & Tiengo, A. (2008). Metformin treatment of rats with diet-induced overweight and hypertriglyceridemia decreases plasma triglyceride concentrations, while decreasing triglyceride and increasing ketone body output by the isolated perfused liver. Acta Diabetologica, 45(3), 143-145. http://dx.doi.org/10.1007/s00592-008-0032-0
Vinod, P. B. (2012). Pathophysiology of diabetic nephropathy. Clinical Queries: Nephrology, 1(2), 121-126. http://dx.doi.org/10.1016/S2211-9477(12)70005-5
Wisutthathum, S., Kamkaew, N., Inchan, A., Chatturong, U., Paracha, T. U., Ingkaninan, K., . . . Chootip, K. (2019). Extract of Aquilaria crassna leaves and mangiferin are vasodilators while showing no cytotoxicity. Journal of Traditional and Complementary Medicine, 9(4), 237-242. http://dx.doi.
org/10.1016/j.jtcme.2018.09.002
Wongwad, Eakkaluk, Pingyod, Chitaporn, Saesong, Tongchai, Waranuch, Neti, Wisuitiprot, Wudtichai, Sritularak, Boonchoo, . . . Ingkaninan, Kornkanok. (2019). Assessment of the bioactive components, antioxidant, antiglycation and anti-inflammatory properties of Aquilaria crassna Pierre ex Lecomte leaves. Industrial Crops and Products, 138, 111448. http://dx.doi.org/10.1016/j.indcrop.2019.06.011
Zelmanovitz, T., Gerchman, F., Balthazar, A. P., Thomazelli, F. C., Matos, J. D., & Canani, L. H. (2009). Diabetic nephropathy. Diabetology & Metabolic Syndrome, 1(1), 10. http://dx.doi.org/10.1186/
1758-5996-1-10
Zhang, S., Xu, H., Yu, X., Wu, Y., & Sui, D. (2017). Metformin ameliorates diabetic nephropathy in a rat model of low-dose streptozotocin-induced diabetes. Experimental and Therapeutic Medicine, 14(1), 383-390. http://dx.doi.org/10.3892/etm.2017.4475
Zhou, C., Yool, A. J., Nolan, J., & Byard, R. W. (2013). Armanni-Ebstein lesions: a need for clarification. The Journal of Forensic Sciences, 58 Suppl 1, S94-98. http://dx.doi.org/10.1111/j.1556-4029.2012.02274.x
Cao, Z., & Cooper, M. E. (2011). Pathogenesis of diabetic nephropathy. Journal of Diabetes Investigation, 2(4), 243-247. http://dx.doi.org/10.1111/j.2040-1124.2011.00131.x
Dahham, S. S., Tabana, Y. M., Iqbal, M. A., Ahamed, M. B., Ezzat, M. O., Majid, A. S., & Majid, A. M. (2015). The Anticancer, Antioxidant and Antimicrobial Properties of the Sesquiterpene beta-Caryophyllene from the Essential Oil of Aquilaria crassna. Molecules, 20(7), 11808-11829. http://dx.doi.org/10.3390/molecules200711808
Davidson, M. B., & Peters, A. L. (1997). An overview of metformin in the treatment of type 2 diabetes mellitus. The American Journal of Medicine, 102(1), 99-110. http://dx.doi.org/10.1016/s0002-9343(96)00353-1
Dineshkumar, B., Mitra, A., & Manjunatha, M. (2010). Studies on the anti-diabetic and hypolipidemic potentials of mangiferin (Xanthone Glucoside) in streptozotocin-induced Type 1 and Type 2 diabetic model rats. International Journal of Advances in Pharmaceutical Sciences, 1, 75-85. http://dx.doi.org/
10.5138/ijaps.2010.0976.1055.01009
Ebstein, W. (1882). Weiteres über Diabetes mellitus, insbesondere über die Complicationdesselben mit Typhus abdominalis. Deutsches Archiv für klinische Medizin, 30, 1-44.
Eppenga, W. L., Lalmohamed, A., Geerts, A. F., Derijks, H. J., Wensing, M., Egberts, A., . . . de Vries, F. (2014). Risk of lactic acidosis or elevated lactate concentrations in metformin users with renal impairment: a population-based cohort study. Diabetes Care, 37(8), 2218-2224. http://dx.doi.org/
10.2337/dc13-3023
Forbes, J. M., Cooper, M. E., Oldfield, M. D., & Thomas, M. C. (2003). Role of advanced glycation end products in diabetic nephropathy. Journal of the American Society of Nephrology, 14(8 Suppl 3), S254-258. http://dx.doi.org/10.1097/01.asn.0000077413.41276.17
Ganogpichayagrai, A., Palanuvej, C., & Ruangrungsi, N. (2017). Antidiabetic and anticancer activities of Mangifera indica cv. Okrong leaves. Journal of Advanced Pharmaceutical Technology & Research, 8(1), 19-24. http://dx.doi.org/10.4103/2231-4040.197371
Hara, H., Ise, Y., Morimoto, N., Shimazawa, M., Ichihashi, K., Ohyama, M., & Iinuma, M. (2008). Laxative effect of agarwood leaves and its mechanism. Bioscience, Biotechnology, and Biochemistry, 72(2), 335-345. http://dx.doi.org/10.1271/bbb.70361
Hardie, D. G. (2008). Role of AMP-activated protein kinase in the metabolic syndrome and in heart disease. Federation of European Biochemical Societies Letters, 582(1), 81-89. http://dx.doi.org/10.1016/j.
febslet.2007.11.018
Hasanvand, A., Amini-Khoei, H., Hadian, M. R., Abdollahi, A., Tavangar, S. M., Dehpour, A. R., . . . Mehr, S. E. (2016). Anti-inflammatory effect of AMPK signaling pathway in rat model of diabetic neuropathy. Inflammopharmacology, 24(5), 207-219. http://dx.doi.org/10.1007/s10787-016-0275-2
Ichiki, H., Miura, T., Kubo, M., Ishihara, E., Komatsu, Y., Tanigawa, K., & Okada, M. (1998). New antidiabetic compounds, mangiferin and its glucoside. The Biological and Pharmaceutical Bulletin, 21(12), 1389-1390. http://dx.doi.org/10.1248/bpb.21.1389
Inzucchi, S. E., Bergenstal, R. M., Buse, J. B., Diamant, M., Ferrannini, E., Nauck, M., . . . European Association for the Study of, Diabetes. (2012). Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care, 35(6), 1364-1379. http://dx.
doi.org/10.2337/dc12-0413
Ishizaki, M., Masuda, Y., Fukuda, Y., Yamanaka, N., Masugi, Y., Shichinohe, K., & Nakama, K. (1987). Renal lesions in a strain of spontaneously diabetic WBN/Kob rats. Acta Diabetologica Latina, 24(1), 27-35. http://dx.doi.org/10.1007/BF02732050
Ito, Tetsuro, Kakino, Mamoru, Tazawa, Shigemi, Oyama, Masayoshi, Maruyama, Hiroe, Araki, Yoko, . . . Iinuma, Munekazu. (2012). Identification of Phenolic Compounds in Aquilaria crassna Leaves Via Liquid Chromatography-Electrospray Ionization Mass Spectroscopy. Food Science and Technology Research, 18(2), 259-262. http://dx.doi.org/10.3136/fstr.18.259
Kang, J., Dai, X. S., Yu, T. B., Wen, B., & Yang, Z. W. (2005). Glycogen accumulation in renal tubules, a key morphological change in the diabetic rat kidney. Acta Diabetologica, 42(2), 110-116. http://dx.doi.org/10.1007/s00592-005-0188-9
Kashihara, N., Haruna, Y., Kondeti, V. K., & Kanwar, Y. S. (2010). Oxidative stress in diabetic nephropathy. Current Medicinal Chemistry, 17(34), 4256-4269. http://dx.doi.org/10.2174/09298671079
3348581
Kawashima, I., & Kirito, K. (2016). Metformin inhibits JAK2V617F activity in MPN cells by activating AMPK and PP2A complexes containing the B56alpha subunit. Experimental Hematology, 44(12), 1156-1165 e1154. http://dx.doi.org/10.1016/j.exphem.2016.08.005
Kock, K. F., & Vestergaard, V. (1994). Armanni-Ebstein lesions of the kidney: diagnostic of death in diabetic coma? Forensic Science International, 67(3), 169-174. http://dx.doi.org/10.1016/0379-0738(94)90087-6
Nielsen, H., Thomsen, J. L., Kristensen, I. B., & Ottosen, P. D. (2003). Accumulation of triglycerides in the proximal tubule of the kidney in diabetic coma. Pathology, 35(4), 305-310. http://dx.doi.org/10.
1080/0031302031000150551
Pal, P. B., Sinha, K., & Sil, P. C. (2014). Mangiferin attenuates diabetic nephropathy by inhibiting oxidative stress mediated signaling cascade, TNFalpha related and mitochondrial dependent apoptotic pathways in streptozotocin-induced diabetic rats. PLoS One, 9(9), e107220. http://dx.doi.org/10.1371/
journal.pone.0107220
Pranakhon, R., Aromdee, C., & Pannangpetch, P. (2015). Effects of iriflophenone 3-C-beta-glucoside on fasting blood glucose level and glucose uptake. Pharmacognosy Magazine, 11(41), 82-89. http://dx.doi.org/10.4103/0973-1296.149711
Pranakhon, R., Pannangpetch, P., & Aromdee, C. (2011). Antihyperglycemic activity of agarwood leaf extracts in STZ-induced diabetic rats and glucose uptake enhancement activity in rat adipocytes. Songklanakarin Journal of Science and Technology, 33(4), 405-410.
Ray, G., Leelamanit, W., Sithisarn, P., & Jiratchariyakul, W. (2014). Antioxidative Compounds from Aquilaria crassna Leaf. Mahidol University Journal of Pharmaceutical Sciences, 41(4), 54-58.
Richy, F. F., Sabido-Espin, M., Guedes, S., Corvino, F. A., & Gottwald-Hostalek, U. (2014). Incidence of lactic acidosis in patients with type 2 diabetes with and without renal impairment treated with metformin: a retrospective cohort study. Diabetes Care, 37(8), 2291-2295. http://dx.doi.org/10.2337/dc14-0464
Ritchie, S., & Waugh, D. (1957). The pathology of Armanni-Ebstein diabetic nephropathy. The American Journal of Pathology, 33(6), 1035-1057.
Saravi, S. S. S., Hasanvand, A., Shahkarami, K., & Dehpour, A. R. (2016). The protective potential of metformin against acetaminophen-induced hepatotoxicity in BALB/C mice. Pharmaceutical Biology, 54(12), 2830-2837. http://dx.doi.org/10.1080/13880209.2016.1185633
Schwetz, V., Eisner, F., Schilcher, G., Eller, K., Plank, J., Lind, A., . . . Eller, P. (2017). Combined metformin-associated lactic acidosis and euglycemic ketoacidosis. Wien Klin Wochenschr, 129(17-18), 646-649. http://dx.doi.org/10.1007/s00508-017-1251-6
Soetikno, V., Watanabe, K., Sari, F. R., Harima, M., Thandavarayan, R. A., Veeraveedu, P. T., . . . Suzuki, K. (2011). Curcumin attenuates diabetic nephropathy by inhibiting PKC-alpha and PKC-beta1 activity in streptozotocin-induced type I diabetic rats. Molecular Nutrition & Food Research, 55(11), 1655-1665. http://dx.doi.org/10.1002/mnfr.201100080
Szkudelski, T. (2001). The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas. Physiological Research, 50(6), 537-546.
Tessari, P., & Tiengo, A. (2008). Metformin treatment of rats with diet-induced overweight and hypertriglyceridemia decreases plasma triglyceride concentrations, while decreasing triglyceride and increasing ketone body output by the isolated perfused liver. Acta Diabetologica, 45(3), 143-145. http://dx.doi.org/10.1007/s00592-008-0032-0
Vinod, P. B. (2012). Pathophysiology of diabetic nephropathy. Clinical Queries: Nephrology, 1(2), 121-126. http://dx.doi.org/10.1016/S2211-9477(12)70005-5
Wisutthathum, S., Kamkaew, N., Inchan, A., Chatturong, U., Paracha, T. U., Ingkaninan, K., . . . Chootip, K. (2019). Extract of Aquilaria crassna leaves and mangiferin are vasodilators while showing no cytotoxicity. Journal of Traditional and Complementary Medicine, 9(4), 237-242. http://dx.doi.
org/10.1016/j.jtcme.2018.09.002
Wongwad, Eakkaluk, Pingyod, Chitaporn, Saesong, Tongchai, Waranuch, Neti, Wisuitiprot, Wudtichai, Sritularak, Boonchoo, . . . Ingkaninan, Kornkanok. (2019). Assessment of the bioactive components, antioxidant, antiglycation and anti-inflammatory properties of Aquilaria crassna Pierre ex Lecomte leaves. Industrial Crops and Products, 138, 111448. http://dx.doi.org/10.1016/j.indcrop.2019.06.011
Zelmanovitz, T., Gerchman, F., Balthazar, A. P., Thomazelli, F. C., Matos, J. D., & Canani, L. H. (2009). Diabetic nephropathy. Diabetology & Metabolic Syndrome, 1(1), 10. http://dx.doi.org/10.1186/
1758-5996-1-10
Zhang, S., Xu, H., Yu, X., Wu, Y., & Sui, D. (2017). Metformin ameliorates diabetic nephropathy in a rat model of low-dose streptozotocin-induced diabetes. Experimental and Therapeutic Medicine, 14(1), 383-390. http://dx.doi.org/10.3892/etm.2017.4475
Zhou, C., Yool, A. J., Nolan, J., & Byard, R. W. (2013). Armanni-Ebstein lesions: a need for clarification. The Journal of Forensic Sciences, 58 Suppl 1, S94-98. http://dx.doi.org/10.1111/j.1556-4029.2012.02274.x
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How to Cite
KHUNCHAI, Sasiprapa et al.
Histopathological Changes of Renal Tubules in Metformin and A. Crassna Leaf Extract treated STZ-induced Diabetic Rats.
Naresuan University Journal: Science and Technology (NUJST), [S.l.], v. 31, n. 1, p. 82-92, dec. 2022.
ISSN 2539-553X.
Available at: <https://www.journal.nu.ac.th/NUJST/article/view/Vol-31-No-1-2023-82-92>. Date accessed: 27 apr. 2024.
doi: https://doi.org/10.14456/nujst.2023.9.