Published 2022-04-28
Safendra Siregar Max Stevanus Bambang Sasongko Nugroho


Objective: To determine the effects breadfruit leaf extract (Artocaptus altilis)in Wistar rats, which had induced renal ischemic-reperfusion injury, with evaluation of serum cystatin C level and kidney histopatologic findings. Material & Methods: A total of 30 Wistar rats, three groups of ten, were included in the study and were performed in Bandung Eijkman Animal Laboratory. In group I (sham group), a right nephrectomy was done. In group II (control), a right nephrectomy was also done and the left renal pedicles were occluded for 60 minutes and reperfused for 60 minutes. In group III (treatment), the treatment was equal with group II, and breadfruit leaf extract (4.75%) was administered intraperitoneally. At the end of the study, a left nephrectomy was performed on all groups. Afterward, serum cystatin C levels and kidney histopathological findings of all rats were examined. Data were analyzed by an unpaired numerically comparative analysis with SPSS 20.0 software. Results: The mean of serum Cystatin C in group I was 3183.2 ± 680.9 pg/dL, group II  was 3776.4 ± 326.7pg/dL, and group III was 3492.7 ± 1.326.7pg/dL. The mean of histopathology renal score was also assessed, group I was 4.4 ± 0.52, group II was 8.6 ± 0.84, and group III was6.3 ± 1.70. Comparative test of serum cystatin C level, using ANOVA test and Benferroni post hoc test, in the treatment group has a p-value of > 0.05, it showed that there were no significant differences on the value of cystatin C level on the treatment group. In correlation test of renal histopathology score, suing Kruskal-Wallis test and Mann-Whitney post hoc test has a p-value of < 0.05, therefore there were significant differences on the mean value of renal histopathology score in the treatment group, with Eta correlation coefficient 0.847. Conclusion: The beneficial effects of breadfruit leaf extract can be attributed to its protective effects on renal cells damage. This treatment has an important role in reducing renal injury resulting from renal ischemia-reperfusion. However, breadfruit leaf extract did not significantly improve renal function based on serum cystatin C level.  



Artocaptus altilis, Renal ischemia-reperfusion injury, Cystatin C, histopathology, kidney


Prodjosudjadi, Wiguno, dan Suhardjono A. End-stage renal disease in Indonesia: treatment development. Ethnicity & Disease. 2009; 19: 33–6.

Bonventre, Joseph V, and Yang Li. Cellular pathophysiology of ischemic acute kidney injury. Journal of Clinical Investigation. 2011; 121(11): 4210–4221

Carden, Donna L, and Granger, D Neil. Pathophysiology of ischemia-reperfusion injury. The Journal of Pathology. 2000; 190(3): 255–266.

Riera M, Torras J, Herrero I, Valles J, et al. Neutrophils accentuate renal cold ischemia-reperfusion injury. Dose-dependent protective effect of a platelet-activating factor receptor antagonist. The Journal of Pharmacology and Experimental Therapeutics. 1997; 280(2): 786–794.

LC Racusen and Nast CC. Renal Histopathology, Urine Culture, in Atlas of diseases of the kidney 2. Oxford. 2004.

Tighe JR. The pathology of renal ischemia. J. Clin. Path. 1997.

SVR Ganeson, IR Husen and Siregar, Safendra. Protective Effect of Sukun Leaf Infusion on Gentamicin Induced Acute Kidney Injury. 2012.

Huk I, Brovkovych V, Nanobash Vili J, Weigel G, et al. Bioflavonoid quercetin scavenges superoxide and increases nitric oxide concentration in ischemia-reperfusion injury: an experimental study. The British Journal of Surgery. 1998; 85(8): 1080–1085.

Küçük A, Yucel M, Erkasap N, Tosun M, et al. The effects of PDE5 inhibitory drugs on renal ischemia/reperfusion injury in rats. Molecular Biology Reports. 2012; 39(10): 9775–9782.

Singh, Amrit Pal, Junemann, Anselm, Muthuraman, Arunachalam, Jaggi, Amteshwar Singh, et al. Animal models of acute renal failure. Pharmacological reports: PR. 2012; 64(1): 31–44.

Wei Q, and Dong Z. Mouse model of ischemic acute kidney injury: technical notes and tricks. AJP: Renal Physiology. 2012; 303(11): F1487–F1494.

Zaher Armaly, Zaid Abassi. Phosphodiesterase-5 Inhibitors: Potential Nephroprotective Agents. Clinical & Experimental Pharmacology. 2014; 4(3).

Mares, Jan, Stejskal, David, Vavrousková, Jitka, Urbánek, Karel, et al. Use of cystatin C determination in clinical diagnostics. Biomedical Papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia. 2003; 147(2): 177–180.

Sohotnik R, Nativ O, Abbasi A, Awad H, et al. Phosphodiesterase-5 inhibition attenuates early renal ischemia-reperfusion-induced acute kidney injury: assessment by quantitative measurement of urinary NGAL and KIM-1. AJP: Renal Physiology. 2013; 304(8): F1099–F1104.

Guzeloglu, Mehmet, Yalcinkaya, Fatih, Atmaca, Soner, Bagriyanik, Alper, et al. The Beneficial Effects of Tadalafil on Renal Ischemia-Reperfusion Injury in Rats’. Urologia Internationalis. 2011; 86(2): 197–203.

Oruc, Ozgur, Inci, Kubilay, Aki, Fazil Tuncay, Zeybek, Dilara, et al. Sildenafil attenuates renal ischemia-reperfusion injury by decreasing leukocyte infiltration. Acta Histochemica. 2010; 112(4): 337–344.

Ozbek, Kerem, Ceyhan, Koksal, Koc, Fatih, Sogut, Erkan, et al. The protective effect of single dose tadalafil in contrast-induced nephropathy: An experimental study. Anadolu Kardiyoloji Dergisi/The Anatolian Journal of Cardiology. 2015; 15(4): 306–310.

Malek, Maryam. Renal ischemia/reperfusion injury; from pathophysiology to treatment. 2017.

Copyright Information
Department of Urology, Faculty of Medicine/Airlangga University