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Year 2025, Volume: 38 Issue: 2, 167 - 178, 30.05.2025

Fatma Kanpalta Mustafaoğlu , Büşra Ertaş , Göksel Şener , Feriha Ercan

https://doi.org/10.5472/marumj.1706664

Abstract

References

  • Bin-Meferij MM, El-Kott AF, Shati AA, Eid RA. Ginger extract ameliorates renal damage in high fat diet-ınduced obesity in rats: Biochemical and ultrastructural study. Int J Morphol 2019; 37: 438-47. doi: 10.4067/S0717.950.2201900.020.0438.
  • Acikel-Elmas M, Cakıcı SE, Dur IR, et al. Protective effects of exercise on heart and aorta in high-fat diet-induced obese rats. Tissue Cell 2019; 57: 57-65. doi: 10.1016/j.tice.2019.01.005.
  • Adedeji TG, Fasanmade AA, Olapade-Olaopa EO. Dietary macronutrients modulate hypertrophy and contractility of the detrusor in an experimental model of bladder obstruction. Pathophysiology 2019; 26: 11-20. doi: 10.1016/j. pathophys.2018.12.003.
  • Avestaei AH, Yaghchiyan M, Ali-Hemmati A, Farhangi MA, Mesgari-Abbasi M, Shahabi P. Histological, metabolic, and inflammatory changes in the renal tissues of high-fat dietinduced obese rats after vitamin D supplementation. Nutr Food Sci 2020; 50: 1135-49. doi: 10.1108/NFS-01-2020-0009.
  • Lakkis JI, Weir MR. Obesity and kidney disease. Prog Cardiovasc Dis 2018; 61: 157-67. doi: 10.1016/j. pcad.2018.07.005.
  • Powers SA, Ryan TE, Pak ES, Fraser MO, McClung JM, Hannan JL. A chronic high-fat diet decreased detrusor mitochondrial respiration and increased nerve-mediated contractions. Neurourol Urodyn 2019; 38: 1524-32. doi: 10.1002/nau.24015.
  • Alhasson F, Seth RK, Sarkar S, et al. High circulatory leptinmediated NOX-2-peroxynitrite-miR21 axis activates mesangial cells and promotes renal inflammatory pathology in nonalcoholic fatty liver disease. Redox Biol 2018; 17: 1-15. doi: 10.1016/j.redox.2018.04.002.
  • Bedard K, Krause KH. The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev 2007; 87: 245-313. doi: 10.1152/physrev.00044.2005.
  • Suzuki S, Arnold LL, Pennington KL, Kakiuchi-Kiyota S, Cohen SM. Effects of coadministration of dietary sodium arsenite and an NADPH oxidase inhibitor on the rat bladder epithelium. Toxicology 2009; 261: 41-6. doi: 10.1016/j. tox.2009.04.042.
  • Meng R, Zhu DL, Bi Y, Yang DH, Wang YP. Apocynin improves insulin resistance through suppressing inflammation in high-fat diet-induced obese mice. Mediators Inflamm 2010; 2010:858735. doi: 10.1155/2010/858735.
  • Fayed MR, El-Naga RN, Akool ES, El-Demerdash E. The potential antifibrotic impact of apocynin and alpha-lipoic acid in concanavalin A-induced liver fibrosis in rats: Role of NADPH oxidases 1 and 4. Drug Discov Ther 2018; 12: 58-67. doi: 10.5582/ddt.2017.01065.
  • Ximenes, VF, Kanegae, MP, Rissato, SR, Galhiane, MS. The oxidation of apocynin catalyzed by myeloperoxidase: Proposal for NADPH oxidase inhibition. Arch Biochem Biophys 2007; 457: 134-41. doi: 10.1016/j.abb.2006.11.010
  • Şener TE, Yüksel M, Özyılmaz-Yay N, et al. Apocynin attenuates testicular ischemia-reperfusion injury in rats. J Pediatr Surg 2015; 50: 1382-7. doi: 10.1016/j.jpedsurg.2014.11.033.
  • Hersek İ, Köroğlu MK, Coşkunlu B, Ertaş B, Şener G, Ercan F. Apocynin ameliorates testicular toxicity in high-fat diet-fed rats by regulating oxidative stress. Clin Exp Health Sci 2023; 13: 75-83. doi: 10.33808/clinexphealthsci.1035133.
  • Koyuncuoğlu T, Yıldırım A, Dertsiz EK, Yüksel M, Ercan F, Yeğen BÇ. Estrogen receptor agonists protect against acetaminophen-induced hepatorenal toxicity in rats. Life Sci 2020; 263: 118561. doi: 10.1016/j.lfs.2020.118561.
  • Koca O, Gokce AM, Akyuz M, Ercan F, Yurdakul N, Karaman MI. A new problem in inflammatory bladder diseases: use of mobile phones! Braz J Urol 2014; 40: 520-5. doi: 10.1590/ S1677-5538.IBJU.2014.04.11.
  • de Souza AC, Gallo CBM, Passos MCDF, et al. Effect of a high-fat diet on the rat bladder wall and bioactive action of Brazil nut oil. Int Braz J Urol 2019; 45(1): 161-68. doi: 10.1590/ S1677-5538.IBJU.2018.0547.
  • Kanpalta Mustafaoglu F, Ertas B, Sen A, Akakin D, Sener G, Ercan F. Myrtus communis l. extract ameliorates high-fat dietinduced kidney and bladder damage by ınhibiting oxidative stress and ınflammation. Eur J Biol 2022; 81: 217-230. doi: 10.26650/EurJBiol.2022.111.1191.
  • de Vries AP, Ruggenenti P, Ruan XZ, et al. Fatty kidney: emerging role of ectopic lipid in obesity-related renal disease. Lancet Diabetes Endocrinol 2014; 2: 417-26. doi: 10.1016/ S2213-8587(14)70065-8.
  • Kashiwagi E, Abe T, Kinoshita F, et al. The role of adipocytokines and their receptors in bladder cancer: expression of adiponectin or leptin is an independent prognosticator. Am J Transl Res 2020; 12: 3033-45.
  • Acikel Elmas M, Ozakpınar OB, Kolgazi M, Sener G, Ercan F. Morphological and biochemical investigation of the healing effects of exercise on high-fat diet-induced kidney and bladder damage. Clin Exp Health Sci 2022; 12: 817-23. doi: 10.33808/ clinexphealthsci.1027516.
  • Acikel Elmas M, Ozgun G, Bingol Ozakpinar O, Guleken Z, Arbak S. Effects of apocynin against monosodium glutamateınduced oxidative damage in rat kidney. Eur J Biol 2022; 81: 231-39. doi: 10.26650/EurJBiol.2022.114.8934.
  • Wu LL, Chiou CC, Chang PY, Wu JT. Urinary 8-OHdG: a marker of oxidative stress to DNA and a risk factor for cancer, atherosclerosis, and diabetics. Clin Chim Acta 2004; 339: 1-9. doi: 10.1016/j.cccn.2003.09.010.
  • Lee M, Zhao H, Liu Xet al. Protective effect of hydroxysafflor yellow a on nephropathy by attenuating oxidative stress and inhibiting apoptosis in induced type 2 diabetes in rat. Oxid Med Cell Longev 2020; 7805393. doi: 10.1155/2020/7805393.
  • Cheng SF, Jiang YH, Kuo HC. Urothelial dysfunction and chronic ınflammation are associated with increased bladder sensation in patients with chronic renal insufficiency. Int Neurourol J. 2018; 22 (Suppl 1): S46-54. doi: 10.5213/ inj.1832814.407.
  • Lai J, Ge M, Shen S, et al. Activation of NFKB-JMJD3 signaling promotes bladder fibrosis via boosting bladder smooth muscle cell proliferation and collagen accumulation. Biochim Biophys Acta Mol Basis Dis 2019; 1865: 2403-10. doi: 10.1016/j.bbadis.2019.05.008.
  • Wang Q, Xie Z, Zhang W, et al. Myeloperoxidase deletion prevents high-fat diet-induced obesity and insulin resistance. Diabetes 2014; 63:4172-85. doi: 10.2337/db14-0026.
  • Kim A, Yu HY, Heo J, et al. Mesenchymal stem cells protect against the tissue fibrosis of ketamine-induced cystitis in rat bladder. Sci Rep 2016; 6: 30881. doi: 10.1038/srep30881.
  • Bondi CD, Manickam N, Lee DY, et al. NAD(P)H oxidase mediates TGF-beta1-induced activation of kidney myofibroblasts. J Am Soc Nephrol 2010; 21: 93-102. doi: 10.1681/ASN.200.902.0146.
  • Junqueira LC, Bignolas G, Brentani RR. Picrosirius staining plus polarization microscopy, a specific method for collagen detection in tissue sections. Histochem J 1979; 11: 447-55. doi: 10.1007/BF01002772.

NADPH oxidase-2 inhibitor apocynin attenuates high-fat diet-induced kidney and bladder injury

Year 2025, Volume: 38 Issue: 2, 167 - 178, 30.05.2025

Fatma Kanpalta Mustafaoğlu , Büşra Ertaş , Göksel Şener , Feriha Ercan

https://doi.org/10.5472/marumj.1706664

Abstract

Objective: This study aimed to evaluate the effects of NADPH oxidase-2 (NOX-2) inhibitor apocynin (APC) on high-fat diet (HFD)-
induced renal and bladder injury.
Materials and Methods: Wistar albino rats were divided into 4 groups: Control, HFD, HFD+dimetyl sulfoxide (DMSO), and HFD+APC.
Rats in HFD, HFD+DMSO, and HFD+APC groups were fed with HFD for sixteen weeks. In the last 4 weeks of the experiment, either
DMSO or APC (25 mg/kg, dissolved in DMSO) was applied to the HFD+DMSO or HFD+APC groups. Lipid profiles and leptin
values were measured in blood serum. Renal and bladder oxidant/antioxidant parameters, histological changes in the tissues, NOX-2-,
nuclear factor kappa B (NF-ĸB)-immunopositive and apoptotic cells were evaluated.
Results: At the end of the experiment, leptin, cholesterol, and triglyceride levels were higher and high-density lipoprotein levels were
lower in the HFD and HFD+DMSO groups compared to controls. In these experimental groups, an increase in malondialdehyde,
8-hydroxy-deoxyguanosine and myeloperoxidase levels and a decrease in glutathione levels, as well as an increase in collagen, NOX-2
– and NFĸ-B-immunopositive and apoptotic cells were found. Also, a deterioration in kidney and bladder morphology was observed.
All these biochemical and histopathological findings improved in the HFD+APC group.
Conclusion: High-fed diet causes renal and bladder injury by increasing NOX-2 activity and inflammation via oxidative stress. APC
might alleviate tissue injury by inhibiting oxidative stress.

Keywords

Apocynin Bladder High-fat diet Kidney Oxidative stress

References

  • Bin-Meferij MM, El-Kott AF, Shati AA, Eid RA. Ginger extract ameliorates renal damage in high fat diet-ınduced obesity in rats: Biochemical and ultrastructural study. Int J Morphol 2019; 37: 438-47. doi: 10.4067/S0717.950.2201900.020.0438.
  • Acikel-Elmas M, Cakıcı SE, Dur IR, et al. Protective effects of exercise on heart and aorta in high-fat diet-induced obese rats. Tissue Cell 2019; 57: 57-65. doi: 10.1016/j.tice.2019.01.005.
  • Adedeji TG, Fasanmade AA, Olapade-Olaopa EO. Dietary macronutrients modulate hypertrophy and contractility of the detrusor in an experimental model of bladder obstruction. Pathophysiology 2019; 26: 11-20. doi: 10.1016/j. pathophys.2018.12.003.
  • Avestaei AH, Yaghchiyan M, Ali-Hemmati A, Farhangi MA, Mesgari-Abbasi M, Shahabi P. Histological, metabolic, and inflammatory changes in the renal tissues of high-fat dietinduced obese rats after vitamin D supplementation. Nutr Food Sci 2020; 50: 1135-49. doi: 10.1108/NFS-01-2020-0009.
  • Lakkis JI, Weir MR. Obesity and kidney disease. Prog Cardiovasc Dis 2018; 61: 157-67. doi: 10.1016/j. pcad.2018.07.005.
  • Powers SA, Ryan TE, Pak ES, Fraser MO, McClung JM, Hannan JL. A chronic high-fat diet decreased detrusor mitochondrial respiration and increased nerve-mediated contractions. Neurourol Urodyn 2019; 38: 1524-32. doi: 10.1002/nau.24015.
  • Alhasson F, Seth RK, Sarkar S, et al. High circulatory leptinmediated NOX-2-peroxynitrite-miR21 axis activates mesangial cells and promotes renal inflammatory pathology in nonalcoholic fatty liver disease. Redox Biol 2018; 17: 1-15. doi: 10.1016/j.redox.2018.04.002.
  • Bedard K, Krause KH. The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev 2007; 87: 245-313. doi: 10.1152/physrev.00044.2005.
  • Suzuki S, Arnold LL, Pennington KL, Kakiuchi-Kiyota S, Cohen SM. Effects of coadministration of dietary sodium arsenite and an NADPH oxidase inhibitor on the rat bladder epithelium. Toxicology 2009; 261: 41-6. doi: 10.1016/j. tox.2009.04.042.
  • Meng R, Zhu DL, Bi Y, Yang DH, Wang YP. Apocynin improves insulin resistance through suppressing inflammation in high-fat diet-induced obese mice. Mediators Inflamm 2010; 2010:858735. doi: 10.1155/2010/858735.
  • Fayed MR, El-Naga RN, Akool ES, El-Demerdash E. The potential antifibrotic impact of apocynin and alpha-lipoic acid in concanavalin A-induced liver fibrosis in rats: Role of NADPH oxidases 1 and 4. Drug Discov Ther 2018; 12: 58-67. doi: 10.5582/ddt.2017.01065.
  • Ximenes, VF, Kanegae, MP, Rissato, SR, Galhiane, MS. The oxidation of apocynin catalyzed by myeloperoxidase: Proposal for NADPH oxidase inhibition. Arch Biochem Biophys 2007; 457: 134-41. doi: 10.1016/j.abb.2006.11.010
  • Şener TE, Yüksel M, Özyılmaz-Yay N, et al. Apocynin attenuates testicular ischemia-reperfusion injury in rats. J Pediatr Surg 2015; 50: 1382-7. doi: 10.1016/j.jpedsurg.2014.11.033.
  • Hersek İ, Köroğlu MK, Coşkunlu B, Ertaş B, Şener G, Ercan F. Apocynin ameliorates testicular toxicity in high-fat diet-fed rats by regulating oxidative stress. Clin Exp Health Sci 2023; 13: 75-83. doi: 10.33808/clinexphealthsci.1035133.
  • Koyuncuoğlu T, Yıldırım A, Dertsiz EK, Yüksel M, Ercan F, Yeğen BÇ. Estrogen receptor agonists protect against acetaminophen-induced hepatorenal toxicity in rats. Life Sci 2020; 263: 118561. doi: 10.1016/j.lfs.2020.118561.
  • Koca O, Gokce AM, Akyuz M, Ercan F, Yurdakul N, Karaman MI. A new problem in inflammatory bladder diseases: use of mobile phones! Braz J Urol 2014; 40: 520-5. doi: 10.1590/ S1677-5538.IBJU.2014.04.11.
  • de Souza AC, Gallo CBM, Passos MCDF, et al. Effect of a high-fat diet on the rat bladder wall and bioactive action of Brazil nut oil. Int Braz J Urol 2019; 45(1): 161-68. doi: 10.1590/ S1677-5538.IBJU.2018.0547.
  • Kanpalta Mustafaoglu F, Ertas B, Sen A, Akakin D, Sener G, Ercan F. Myrtus communis l. extract ameliorates high-fat dietinduced kidney and bladder damage by ınhibiting oxidative stress and ınflammation. Eur J Biol 2022; 81: 217-230. doi: 10.26650/EurJBiol.2022.111.1191.
  • de Vries AP, Ruggenenti P, Ruan XZ, et al. Fatty kidney: emerging role of ectopic lipid in obesity-related renal disease. Lancet Diabetes Endocrinol 2014; 2: 417-26. doi: 10.1016/ S2213-8587(14)70065-8.
  • Kashiwagi E, Abe T, Kinoshita F, et al. The role of adipocytokines and their receptors in bladder cancer: expression of adiponectin or leptin is an independent prognosticator. Am J Transl Res 2020; 12: 3033-45.
  • Acikel Elmas M, Ozakpınar OB, Kolgazi M, Sener G, Ercan F. Morphological and biochemical investigation of the healing effects of exercise on high-fat diet-induced kidney and bladder damage. Clin Exp Health Sci 2022; 12: 817-23. doi: 10.33808/ clinexphealthsci.1027516.
  • Acikel Elmas M, Ozgun G, Bingol Ozakpinar O, Guleken Z, Arbak S. Effects of apocynin against monosodium glutamateınduced oxidative damage in rat kidney. Eur J Biol 2022; 81: 231-39. doi: 10.26650/EurJBiol.2022.114.8934.
  • Wu LL, Chiou CC, Chang PY, Wu JT. Urinary 8-OHdG: a marker of oxidative stress to DNA and a risk factor for cancer, atherosclerosis, and diabetics. Clin Chim Acta 2004; 339: 1-9. doi: 10.1016/j.cccn.2003.09.010.
  • Lee M, Zhao H, Liu Xet al. Protective effect of hydroxysafflor yellow a on nephropathy by attenuating oxidative stress and inhibiting apoptosis in induced type 2 diabetes in rat. Oxid Med Cell Longev 2020; 7805393. doi: 10.1155/2020/7805393.
  • Cheng SF, Jiang YH, Kuo HC. Urothelial dysfunction and chronic ınflammation are associated with increased bladder sensation in patients with chronic renal insufficiency. Int Neurourol J. 2018; 22 (Suppl 1): S46-54. doi: 10.5213/ inj.1832814.407.
  • Lai J, Ge M, Shen S, et al. Activation of NFKB-JMJD3 signaling promotes bladder fibrosis via boosting bladder smooth muscle cell proliferation and collagen accumulation. Biochim Biophys Acta Mol Basis Dis 2019; 1865: 2403-10. doi: 10.1016/j.bbadis.2019.05.008.
  • Wang Q, Xie Z, Zhang W, et al. Myeloperoxidase deletion prevents high-fat diet-induced obesity and insulin resistance. Diabetes 2014; 63:4172-85. doi: 10.2337/db14-0026.
  • Kim A, Yu HY, Heo J, et al. Mesenchymal stem cells protect against the tissue fibrosis of ketamine-induced cystitis in rat bladder. Sci Rep 2016; 6: 30881. doi: 10.1038/srep30881.
  • Bondi CD, Manickam N, Lee DY, et al. NAD(P)H oxidase mediates TGF-beta1-induced activation of kidney myofibroblasts. J Am Soc Nephrol 2010; 21: 93-102. doi: 10.1681/ASN.200.902.0146.
  • Junqueira LC, Bignolas G, Brentani RR. Picrosirius staining plus polarization microscopy, a specific method for collagen detection in tissue sections. Histochem J 1979; 11: 447-55. doi: 10.1007/BF01002772.
There are 30 citations in total.

Details

Primary Language English
Subjects Surgery (Other)
Journal Section Original Research
Authors

Fatma Kanpalta Mustafaoğlu 0000-0001-9832-6938

Büşra Ertaş 0000-0001-8374-1098

Göksel Şener 0000-0001-7444-6193

Feriha Ercan 0000-0003-2339-5669

Publication Date May 30, 2025
Submission Date August 8, 2024
Acceptance Date February 7, 2025
Published in Issue Year 2025 Volume: 38 Issue: 2

Cite

APA Kanpalta Mustafaoğlu, F., Ertaş, B., Şener, G., Ercan, F. (2025). NADPH oxidase-2 inhibitor apocynin attenuates high-fat diet-induced kidney and bladder injury. Marmara Medical Journal, 38(2), 167-178. https://doi.org/10.5472/marumj.1706664
AMA Kanpalta Mustafaoğlu F, Ertaş B, Şener G, Ercan F. NADPH oxidase-2 inhibitor apocynin attenuates high-fat diet-induced kidney and bladder injury. Marmara Med J. May 2025;38(2):167-178. doi:10.5472/marumj.1706664
Chicago Kanpalta Mustafaoğlu, Fatma, Büşra Ertaş, Göksel Şener, and Feriha Ercan. “NADPH Oxidase-2 Inhibitor Apocynin Attenuates High-Fat Diet-Induced Kidney and Bladder Injury”. Marmara Medical Journal 38, no. 2 (May 2025): 167-78. https://doi.org/10.5472/marumj.1706664.
EndNote Kanpalta Mustafaoğlu F, Ertaş B, Şener G, Ercan F (May 1, 2025) NADPH oxidase-2 inhibitor apocynin attenuates high-fat diet-induced kidney and bladder injury. Marmara Medical Journal 38 2 167–178.
IEEE F. Kanpalta Mustafaoğlu, B. Ertaş, G. Şener, and F. Ercan, “NADPH oxidase-2 inhibitor apocynin attenuates high-fat diet-induced kidney and bladder injury”, Marmara Med J, vol. 38, no. 2, pp. 167–178, 2025, doi: 10.5472/marumj.1706664.
ISNAD Kanpalta Mustafaoğlu, Fatma et al. “NADPH Oxidase-2 Inhibitor Apocynin Attenuates High-Fat Diet-Induced Kidney and Bladder Injury”. Marmara Medical Journal 38/2 (May 2025), 167-178. https://doi.org/10.5472/marumj.1706664.
JAMA Kanpalta Mustafaoğlu F, Ertaş B, Şener G, Ercan F. NADPH oxidase-2 inhibitor apocynin attenuates high-fat diet-induced kidney and bladder injury. Marmara Med J. 2025;38:167–178.
MLA Kanpalta Mustafaoğlu, Fatma et al. “NADPH Oxidase-2 Inhibitor Apocynin Attenuates High-Fat Diet-Induced Kidney and Bladder Injury”. Marmara Medical Journal, vol. 38, no. 2, 2025, pp. 167-78, doi:10.5472/marumj.1706664.
Vancouver Kanpalta Mustafaoğlu F, Ertaş B, Şener G, Ercan F. NADPH oxidase-2 inhibitor apocynin attenuates high-fat diet-induced kidney and bladder injury. Marmara Med J. 2025;38(2):167-78.
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