Azadirachta excelsa Improves Renal Morphology and Function in Streptozotocin Induced-Diabetic Sprague Dawley Rats

Authors

  • Nur Syimal Aain AZMI Faculty of Applied Sciences, Universiti Teknologi MARA, Selangor, Malaysia
  • Nooraain HASHIM Faculty of Applied Sciences, Universiti Teknologi MARA, Selangor, Malaysia
  • Nurdiana SAMSULRIZAL Faculty of Applied Sciences, Universiti Teknologi MARA, Selangor, Malaysia
  • Noor Syaffinaz NOOR Faculty of Applied Sciences, Universiti Teknologi MARA, Selangor, Malaysia
  • Mohamad ZIN Faculty of Applied Sciences, Universiti Teknologi MARA, Selangor, Malaysia

DOI:

https://doi.org/10.48048/wjst.2021.6238

Keywords:

Nephropathy, Streptozotocin, MDA, GPx, SOD, Kidney function parameters

Abstract

Long term diabetes mellitus (DM) is associated with serious complications such as nephropathy. Previous studies revealed the ability of A. excelsa leaf extract treatment to reduce fasting blood glucose (FBG) in streptozotocin (STZ)-induced diabetic rats. The aim of this study was to determine the effect of A. excelsa extract in delaying the progression of diabetic nephropathy by evaluating the kidney structure and function. The effects were compared with 2 positive controls, which were metformin (standard drug) and quercetin (plant active compound). Induction of diabetic conditions was conducted by the intraperitoneal (IP) injection of STZ (60 mg/kg bwt) in male Sprague Dawley rats. The experimental animals were grouped into: 1) normal control (NC, saline); 2) diabetic control (DC, saline); 3) metformin-treated diabetic rats (DMET, 1000 mg/kg bwt); 4) quercetin-treated diabetic rats (DQ, 40 mg/kg bwt), and 5) A. excelsa-treated diabetic rats (DAE, 250 mg/kg bwt). All treatments were given once daily for 8 weeks through oral gavage. The inter-relation between the changes in the fasting blood glucose and kidney oxidative stress, structure, and function was evaluated. The results showed a significant increase (p < 0.05) of MDA and SOD level and a decrease (p < 0.05) of GPx levels, plus distortion of renal morphology among the DC and DMET groups. Meanwhile, both DQ and DAE groups showed significant reduction (p < 0.05) of MDA levels and elevation (p < 0.05) of SOD and GPx levels. The quercetin and A. excelsa treatments also improved the kidney function parameters and morphological changes of the diabetic rats. These findings indicate that quercetin and A. excelsa possess renal therapeutic effects.

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Author Biography

Nur Syimal Aain AZMI, Faculty of Applied Sciences, Universiti Teknologi MARA, Selangor, Malaysia

School of Biology

References

ID Federation. IDF Diabetes Atlas. 6th ed. International Diabetes Federation, Brussels, 2013.

ME Molitch, RA DeFronzo, MJ Franz, WF Keane, CE Mogensen, HH Parving, MW Steffes and American Diabetes Association. Nephropathy in Diabetes. Diabetes Care. 2004; 27, S79-83.

AC Webster, EV Nagler, RL Morton and P Masson. Chronic kidney disease. Lancet 2017; 389, 1238-52.

D Intiso. The rehabilitation role in chronic kidney and end stage renal disease. Kidney Blood Pres. Res. 2014; 39, 180-8.

LS Hooi, LM Ong, G Ahmad, S Bavanandan, NA Ahmad, BM Naidu and MFM Yusoff. A population-based study measuring the prevalence of chronic kidney disease among adults in West Malaysia. Kidney Int. 2013; 84, 1034-40.

S Aronoff, K Berkowitz, B Shreiner and L Want. Glucose metabolism and regulation: Beyond insulin and glucagon. Diabetes Spectrum 2004; 17, 183-90.

LC Plantinga, DC Crews, J Coresh, ER Miller, R Saran, J Yee, E Hedgeman, M Pavkov, MS Eberhard, DE Williams and NR Powe. Prevalence of chronic kidney disease in US adults with undiagnosed diabetes or prediabetes. Clin. J. Am. Soc. Nephrol. 2010; 5, 673-82.

MY Donath, SE and Shoelson. Type 2 diabetes as an inflammatory disease. Nat. Rev. Immunol. 2011; 11, 98-107.

NR Hill, ST Fatoba, JL Oke, JA Hirst, CA O’Callaghan, DS Lasserson and FR Hobbs. Global prevalence of chronic kidney disease–a systematic review and meta-analysis. PloS One 2016; 11, e0158765.

G Vessal, M Akmali, P Najafi, MR Moein and MM Sagheb. Silymarin and milk thistle extract may prevent the progression of diabetic nephropathy in streptozotocin-induced diabetic rats. Ren. Fail. 2010; 32, 733-9.

V Lobo, A Patil, A Phatak and N Chandra. Free radicals, antioxidants and functional foods: Impact on human health. Pharmacogn. Rev. 2010; 4, 118-26.

S Fakhruddin, W Alanazi and KE Jackson. Diabetes-induced reactive oxygen species: Mechanism of their generation and role in renal injury. J. Diabetes Res. 2017; 2017, 8379327.

K Das and A Roychoudhury. Reactive oxygen species (ROS) and response of antioxidants as ROS-scavengers during environmental stress in plants. Front. Environ. Sci. 2014; 2, 53.

BK Tiwari, KB Pandey, AB Abidi and SI Rizvi. Markers of oxidative stress during diabetes mellitus. J. Biomarkers 2013, 2013.

J Dennis and P Witting. Protective role for antioxidants in acute kidney disease. Nutrients 2017; 9, 718.

S Chirumbol. The role of quercetin, flavonols and flavones in modulating inflammatory cell function. Inflammat. Allergy-Drug Targets 2010; 9, 263-85.

Y Li, J Yao, C Han, J Yang, M Chaudhry, S Wang and Y Yin. Quercetin, inflammation and immunity. Nutrients 2016; 8, 167.

RA Rifaai, NF El-Tahawy, EA Saber and R Ahmed. Effect of quercetin on the endocrine pancreas of the experimentally induced diabetes in male albino rats: A histological and immunohistochemical study. J. Diabetes Metabol. 2012; 3, 2.

M Edremıtlıoğlu, MF Andıç, DB Sayin, O Korkut and U Kisa. Quercetin, a powerful antioxidant bioflavonoid, attenuates renal dysfunction in long-term experimental diabetes mellitus. Marmara Med. J. 2011; 24, 88-99.

NSNM Zin, N Hashim, N Samsulrizal and NS Azmi. The protective effect of Azadirachta excelsa leaves extract and quercetin treatment on the learning and memory impairments in relation with insulin and amylin levels in the brain of streptozotocin-induced diabetic rats. J. King Saud Univ. Sci. 2019; 31, 299-307.

S Nurdiana, MK Shukri, EJ Jega and NS Izzati. Antidiabetic activity of Azadirachta excelsa extract on alloxan induced diabetic rats. Open Conf. Proc. J. 2013; 4, 49-52.

B Cui, H Chai, HL Constant, T Santisuk, V Reutrakul, CW Beecher, NR Farnsworth, GA Cordell, JM Pezzuto and AD Kinghorn. Limonoids from Azadirachta excelsa. Phytochemistry 1998; 47, 1283-7.

NI Shafie, N Samsulrizal, NA Sopian, MA Rajion, GY Meng, MM Ajat and H Ahmad. Qualitative phytochemical screening and GC-MS profiling of Azadirachta excelsa leaf extract. Malays. Appl. Biol. 2015; 44, 87-92.

S Nurdiana, AN Haziqah, MNE Khairunnisa, SN Izzati, Y Norashirene and IN Hilwani. Attenuation of pancreatic histology, hematology and biochemical parameters in Type 2 diabetic rats treated with Azadirachta excelsa. Int. J. Agr. Biosystems Eng. 2014; 8, 613-6.

SN Izzati, S Nurdiana, A Hafandi, AHM Zakihalani, MJ Norashirene and MHS Khairiyah. Antioxidant and hypoglycemic activities of Azadirachta excelsa in diabetic rats. In: Proceedings of the IEEE Symposium on Business, Engineering and Industrial Applications 2013. Kuching, 2013, p. 63.

MA Fortes, CH Pinheiro, L Guimarães‐Ferreira, KF Vitzel, DA Vasconcelos and R Curi. Overload‐induced skeletal muscle hypertrophy is not impaired in STZ‐diabetic rats. Physiol. Rep. 2015; 3, e12457.

M Gurukar, S Mahadevamma and ND Chilkunda. Renoprotective effect of Cocciniaindica fruits and leaves in experimentally induced diabetic rats. J. Med. Food. 2013; 16, 839-46.

Y Dong, T Jing, Q Meng, C Liu, S Hu, Y Ma, Y Liu, J Lu, Y Cheng, D Wang and L Teng. Studies on the antidiabetic activities of Cordycepsmilitaris extract in diet-streptozotocin-induced diabetic Sprague-Dawley rats. BioMed Res. Int. 2014; 2014, 160980.

SN Mestry, JB Dhodi, SB Kumbhar and AR Juvekar. Attenuation of diabetic nephropathy in streptozotocin-induced diabetic rats by Punicagranatum Linn. leaves extract. J. Tradit. Complement. Med. 2017; 7, 273-80.

RA Rifaai, NF El-Tahawy, EA Saber and R Ahmed. Effect of quercetin on the endocrine pancreas of the experimentally induced diabetes in male albino rats: a histological and immunohistochemical study. J. Diabetes Metab. 2012; 3, 1000182.

PH Miranda-Osorio, AE Castell-Rodríguez, J Vargas-Mancilla, CA Tovilla-Zárate, JL Ble-Castillo, DE Aguilar-Domínguez, IE Juárez-Rojop and JC Díaz-Zagoya. Protective action of Carica papaya on β-cells in streptozotocin-induced diabetic rats. Int. J. Environ. Res. Public Health 2016; 13, 446.

R Premanath, N Lakshmidevi, K Jayashree and RN Suresh. Evaluation of anti-diabetic effect of Trigonella foenumgraecum Linn. Leaf extract in streptozotocin induced diabetic rats. Int. J. Diabetes Develop. Countries 2012; 32, 138-44.

NA Qinna and AA Badwan. Impact of streptozotocin on altering normal glucose homeostasis during insulin testing in diabetic rats compared to normoglycemic rats. Drug Des. Dev. Ther. 2016; 9, 2515.

A Tahara, A Matsuyama‐Yokono, R Nakano, Y Someya and M Shibasaki. Hypoglycaemic effects of antidiabetic drugs in streptozotocin‐nicotinamide‐induced mildly diabetic and streptozotocin‐induced severely diabetic rats. Basic Clin. Pharmacol. Toxicol. 2008; 103, 560-8.

AD Kandhare, KS Raygude, VS Kumar, AR Rajmane, A Visnagri, AE Ghule, P Ghosh, SL Badole and SL Bodhankar. Ameliorative effects quercetin against impaired motor nerve function, inflammatory mediators and apoptosis in neonatal streptozotocin-induced diabetic neuropathy in rats. Biomed. Aging Pathol. 2012; 2, 173-86.

S Kimura, T Inoguchi, H Yokomizo, Y Maeda, N Sonoda and R Takayanagi. Randomized comparison of pitavastatin and pravastatin treatment on the reduction of urinary albumin in patients with type 2 diabetic nephropathy. Diabetes Obes. Metab. 2012; 14, 666-9.

RN Hardwick, CD Fisher, MJ Canet, AD Lake and NJ Cherrington. Diversity in antioxidant response enzymes in progressive stages of human non-alcoholic fatty liver disease. Drug Metab. Dispos. 2010; 38, 2293-301.

H Eslami, RA Batavani, S Asri-Rezaei and R Hobbenaghi. Changes of stress oxidative enzymes in rat mammary tissue, blood and milk after experimental mastitis induced by E. coli lipopolysaccharide. Vet. Res. Forum 2015; 6, 131-6.

KK Mali, RJ Dias, VD Havaldar and SJ Yadav. Antidiabetic effect of garcinol on streptozotocin-induced diabetic rats. Indian J. Pharmaceut. Sci. 2017; 79, 463-8.

HS Alnahdi, NO Ayaz, AM Mohamed, IA Sharaf and NM Alshehri. Modulating impacts of quercetin and/or lactoferrin on diabetic nephropathy and cardiomyopathy induced rats. Int. J. Pharmaceut. Res. Allied Sci. 2017; 6, 128-37.

SH Jo, EH Ka, HS Lee, E Apostolidis, HD Jang and YI Kwon. Comparison of antioxidant potential and rat intestinal a-glucosidases inhibitory activities of quercetin, rutin, and isoquercetin. Int. J. Appl. Res. Nat. Prod. 2009; 2, 52-60.

JH Kim, JM Kang, HN Choi, SM Jeong, YM Lee and JI Kim. Quercetin attenuates fasting and postprandial hyperglycemia in animal models of diabetes mellitus. Nut. Res. Pract. 2011; 5, 107-11.

EA Mohamed, M., Ahmad, LF Ang, M Asmawi and MF Yam. Evaluation of α-glucosidase inhibitory effect of 50% ethanolic standardized extract of Orthosiphonstamineusbenth in normal and streptozotocin-induced diabetic rats. Evid. Based Complement. Alternat. Med. 2015; 2015, 754931.

C Serra-Barcellona, NC Habib, SM Honoré, SS Sánchez and SB Genta. Enhydrin regulates postprandial hyperglycemia in diabetic rats by inhibition of α-glucosidase activity. Plant Foods Hum. Nutr. 2017; 72, 156-60.

S Nurdiana, KM Shukri, JE Jega and SN Izzati. Lowering blood glucose effect of Azadirachta excelsa leaves extract. Nat. Prod. Indian J. 2013; 9, 363-6.

PS Sellamuthu, P Arulselvan, S Kamalraj, S Fakurazi and M Kandasamy. Protective nature of mangiferin on oxidative stress and antioxidant status in tissues of streptozotocin-induced diabetic rats. ISRN Pharmacol. 2013; 2013, 750109.

A Aboonabi, A Rahmat and F Othman. Antioxidant effect of pomegranate against streptozotocin-nicotinamide generated oxidative stress induced diabetic rats. Toxicol. Rep. 2014; 1, 915-22.

JC Jha, C Banal, BS Chow, ME Cooper and K Jandeleit-Dahm. Diabetes and kidney disease: Role of oxidative stress. Antioxidants Redox Signal. 2016; 25, 657-84.

A Zarei, S Changizi-Ashtiyani, S Taheri and M Ramezani. A quick overview on some aspects of endocrinological and therapeutic effects of Berberis vulgaris L. Avicenna J. Phytomed. 2015; 5, 485-97.

N Karim, N Jeenduang and J Tangpong. Renoprotective effects of xanthone derivatives from garcinia mangostana against high fat diet and streptozotocin-induced type II diabetes in mice. Walailak J. Sci. & Tech. 2016; 15, 107-16.

S Chaudhary, P Ganjoo, S Raiusddin and S Parvez. Nephroprotective activities of quercetin with potential relevance to oxidative stress induced by valproic acid. Protoplasma 2015; 252, 209-17.

J Santos and LS Martins. Estimating glomerular filtration rate in kidney transplantation: Still searching for the best marker. World J. Nephrol. 2015; 4, 345-53.

SC Thomson, A Kashkouli and P Singh. Glucagon-like peptide-1 receptor stimulation increases GFR and suppresses proximal reabsorption in the rat. Am. J. Physiol. Renal Physiol. 2013; 304, F137-F144.

P Palatini, F Dorigatti, F Saladini, E Benetti, L Mos, A Mazzer, G Zanata, G Garavelli and E Casiglia. Factors associated with glomerular hyperfiltration in the early stage of hypertension. Am. J. Hypertens. 2012; 25, 1011-6.

EL Schiffrin, ML Lipman and JF Mann. Chronic kidney disease: Effects on the cardiovascular system. Circulation 2007; 116, 85-97.

S Gowda, PB Desai, SS Kulkarni, VV Hull, AA Math and SN Vernekar. Markers of renal function tests. N. Am. J. Med. Sci. 2010; 2, 170-3.

E Tynkevich, M Flamant, JP Haymann, M Metzger, E Thervet, F Vrtovsnik, P Houillier, M Froissart, B Stengel and JJ Boffa. Decrease in urinary creatinine excretion in early stage chronic kidney disease. PloS One 2014; 9, e111949.

B Zhu, X Wu, Y Bi and Y Yang. Effect of bilirubin concentration on the risk of diabetic complications: A meta-analysis of epidemiologic studies. Sci. Rep. 2017; 7, 41681.

AC Boon, AK Lam, V Gopalan, IF Benzie, D Briskey, JS Coombes, RG Fassett and AC Bulmer. Endogenously elevated bilirubin modulates kidney function and protects from circulating oxidative stress in a rat model of adenine-induced kidney failure. Sci. Rep. 2015; 5, 15482.

B Alvarez-Lario and J Macarron-Vicente. Is there anything good in uric acid? QJM: Int. J. Med. 2011; 104, 1015-24.

G Ragab, M Elshahaly and T Bardin. Gout: An old disease in new perspective - A review. J. Adv. Res. 2017; 8, 495-511.

CW Tsai, SY Lin, CC Kuo and CC Huang. Serum uric acid and progression of kidney disease: A longitudinal analysis and mini-review. PloS One 2017; 12, e0170393.

A Arya, MM Al-Obaidi, N Shahid, MI Noordin, CY Looi, WF Wong and MR Mustafa. Synergistic effect of quercetin and quinic acid by alleviating structural degeneration in the liver, kidney and pancreas tissues of STZ-induced diabetic rats: A mechanistic study. Food Chem. Toxicol. 2014; 71, 183-96.

DE Odiase and FA Ominiabohs. Protective effects of aqueous extract of cinnamon on diabetes-induced nephrotoxicity in wistar rats. J. Appl. Sci. Environ. Manag. 2017; 21, 504-8.

M Pourghasem, H Shafi and Z Babazadeh. Histological changes of kidney in diabetic nephropathy. Caspian J. Intern Med. 2015; 6, 120-7.

SO Bashir. Hepatoprotective role for quercetin in diabetic rats: Hypolipidemic and antioxidant effects. Med. J. Cairo. Univ. 2014; 82, 169-78.

Y Ishikawa and M Kitamura. Bioflavonoid quercetin inhibits mitosis and apoptosis of glomerular cells in vitro and in vivo. Biochem. Biophy. Res. Comm. 2000; 279, 629-34.

M Erboga, C Aktas, ZF Erboga, YB Donmez and A Gurel. Quercetin ameliorates methotrexate-induced renal damage, apoptosis and oxidative stress in rats. Ren. Fail. 2015; 37, 1492-7.

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Published

2020-12-01

How to Cite

AZMI, N. S. A. ., HASHIM, N. ., SAMSULRIZAL, N. ., NOOR, N. S. ., & ZIN, M. . (2020). Azadirachta excelsa Improves Renal Morphology and Function in Streptozotocin Induced-Diabetic Sprague Dawley Rats. Walailak Journal of Science and Technology (WJST), 17(12), 1307–1320. https://doi.org/10.48048/wjst.2021.6238