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Journals / Osmangazi Tıp Dergisi / 2026 / Cilt: 48 Sayı: 4

Biochemical and Histological Evaluation of The Impacts of Conivaptan and Boric Acid on Ischemia-induced Tissue Injury

Konivaptan ve Borik Asidin İskemi Kaynaklı Doku Hasarı Üzerindeki Etkilerinin Biyokimyasal ve Histolojik Açıdan Değerlendirilmesi

Betül Can(ESKİŞEHİR OSMANGAZİ ÜNİVERSİTESİ, TIP FAKÜLTESİ)0000-0001-8430-5298
Fatih Kar(KÜTAHYA SAĞLIK BİLİMLERİ ÜNİVERSİTESİ, TIP FAKÜLTESİ, TEMEL TIP BİLİMLERİ BÖLÜMÜ, BİYOKİMYA ANABİLİM DALI)0000-0001-8356-9806
Ezgi Kar(KÜTAHYA SAĞLIK BİLİMLERİ ÜNİVERSİTESİ, SAĞLIK BİLİMLERİ FAKÜLTESİ, BESLENME VE DİYETETİK BÖLÜMÜ)0000-0003-2134-4067
Mete Özkoç(GİRNE ÜNİVERSİTESİ, TIP FAKÜLTESİ, TEMEL TIP BİLİMLERİ BÖLÜMÜ, TIBBİ BİYOKİMYA ANABİLİM DALI)0000-0003-3557-4349
Hakan Şentürk(ESKİŞEHİR OSMANGAZİ ÜNİVERSİTESİ, FEN-EDEBİYAT FAKÜLTESİ, BİYOLOJİ BÖLÜMÜ, GENEL BİYOLOJİ ANABİLİM DALI)0000-0002-6199-8594
Dilek Burukoğlu Dönmez(ESKİŞEHİR OSMANGAZİ ÜNİVERSİTESİ, TIP FAKÜLTESİ, TEMEL TIP BİLİMLERİ BÖLÜMÜ, HİSTOLOJİ VE EMBRİYOLOJİ ANABİLİM DALI)0000-0002-6454-4424
Güngör Kanbak(ESKİŞEHİR OSMANGAZİ ÜNİVERSİTESİ, TIP FAKÜLTESİ, TEMEL TIP BİLİMLERİ BÖLÜMÜ, BİYOKİMYA ANABİLİM DALI)0000-0001-7984-3649
İ. Özkan Alataş(ESKİŞEHİR OSMANGAZİ ÜNİVERSİTESİ, TIP FAKÜLTESİ, TEMEL TIP BİLİMLERİ BÖLÜMÜ, BİYOKİMYA ANABİLİM DALI)0000-0002-1753-8873
Pages
590–607
Publication Date
2026-06-09
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AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

Our findings suggest that CON and BA exhibit anti-inflammatory and antioxidant properties in the early phase of postischemic injury process and may be effective in attenuating distant organ damage following renal I/R injury.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:Ischemia-reperfusion (I/R) injury, which is a major cause of acute kidney injury (AKI), involves complicated pathophysiological process triggered by oxidative and inflammatory mechanisms.
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Key Findings & Data:Accordingly, rats were divided into the groups: Control (sham-operated), Ischemia–reperfusion (I/R), I/R + Dimethyl sulfoxide (I/R + DMSO) I/R + Conivaptan (I/R + CON), and I/R + Conivaptan + Boric acid (I/R + CON + BA).
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Conclusion & Impact:Our findings suggest that CON and BA exhibit anti-inflammatory and antioxidant properties in the early phase of postischemic injury process and may be effective in attenuating distant organ damage following renal I/R injury.
🔬Design:Modeling & Simulation
📍Scope:Comprehensive Sample
⚙️Variables:Borik asit · Konivaptan · İnflamasyon

Abstract

Ischemia-reperfusion (I/R) injury, which is a major cause of acute kidney injury (AKI), involves complicated pathophysiological process triggered by oxidative and inflammatory mechanisms. This process adversely affects kidneys and distant organs/systems, potentially leading to multiple organ failure. Therefore, experimental studies targeting renal I/R injury mechanisms are needed to mitigate local and distant organ damage. We established an experimental renal I/R rat model to mimic the clinical presentation of AKI and evaluated the potential damage-preventive effects of conivaptan (CON) and boric acid (BA) on kidneys and distant tissues (liver, brain, heart, pancreas, testis, spleen). Accordingly, rats were divided into the groups: Control (sham-operated), Ischemia–reperfusion (I/R), I/R + Dimethyl sulfoxide (I/R + DMSO) I/R + Conivaptan (I/R + CON), and I/R + Conivaptan + Boric acid (I/R + CON + BA). TAS, TOS, and total thiol levels, which indicated oxidant and antioxidant redox status, were measured in blood samples, and the oxidative stress index was calculated. Inflammation-related cytokines (TNF-α, interleukin (IL)-6, IL-10, IL-35, and chemerin) were analysed through ELISA and/or RT-PCR. Furthermore, serum enzyme activities, lipid-profile, and albumin levels were determined. Tissue samples were examined histologically using Hematoxylin-Eosin staining. Renal I/R injury significantly increased systemic oxidative stress, exacerbated renal inflammation, and induced distant organ damage. Treatment with CON and BA demonstrated protective effects by reducing oxidative stress and modulating inflammatory responses without inducing toxicity in the postischemic period. Our findings suggest that CON and BA exhibit anti-inflammatory and antioxidant properties in the early phase of postischemic injury process and may be effective in attenuating distant organ damage following renal I/R injury.

Özet

Akut böbrek hasarının (ABH) başlıca nedenlerinden biri olan iskemi-reperfüzyon (İ/R) hasarı, oksidatif ve inflamatuar mekanizmaların tetiklendiği kompleks patofizyolojik süreçleri içermektedir. Bu süreçler, böbrek ve uzak organ/sistemleri olumsuz etkileyerek çoklu organ yetmezliğine yol açabilmektedir. Bu nedenle, lokal ve uzak organ hasarını azaltmaya yönelik, böbrek İ/R hasarı mekanizmalarını hedef alan deneysel çalışmaların planlanması önemli bir ihtiyaçtır. Bu çalışmada, ABH kliniğini yansıtmak için deneysel bir böbrek İ/R sıçan modeli oluşturulmuştur; konivaptan (CON) ve borik asidin (BA) böbrekler ve uzak dokular (karaciğer, beyin, kalp, pankreas, testis, dalak) üzerindeki potansiyel hasar önleyici etkileri araştırılmıştır. Buna göre, sıçanlar Kontrol (sham-opere), İskemi-reperfüzyon (I/R), I/R + Dimetilsülfoksit (I/R + DMSO), I/R + Konivaptan (I/R + CON) ve I/R + Konivaptan + Borik asit (I/R + CON + BA) olmak üzere gruplara ayrılmıştır. Oksidan ve antioksidan redoks durumunu gösteren TAS, TOS ve total tiyol düzeyleri kan örneklerinde ölçülmüştür ve oksidatif stres indeksi hesaplanmıştır. İnflamasyonla ilişkili sitokinler (TNF-α, interlökin (IL)-6, IL-10, IL-35 ve kemerin) ELISA ve/veya RT-PCR ile analiz edilmiştir. Ayrıca, serum enzim aktiviteleri, lipit profili ve albümin düzeyleri belirlenmiştir. Doku örnekleri Hematoksilen-Eozin boyama kullanılarak histolojik olarak incelenmiştir. Çalışmamızda böbrek I/R hasarının sistemik oksidatif stresi önemli ölçüde artırdığı, böbrek inflamasyonunu şiddetlendirdiği ve uzak organ hasarını indüklediği gözlenmiştir. CON ve BA tedavisi, iskemi sonrası dönemde toksisiteye neden olmadan oksidatif stresi azaltarak ve inflamasyon yanıtlarını düzenleyerek koruyucu etki göstermiştir. Bulgularımız, CON ve BA'nın iskemi sonrası hasar sürecinin erken evresinde anti-inflamatuar ve antioksidan özellikler gösterdiğini ve böbrek I/R hasarını takiben uzak organ hasarını hafifletmede etkili olabileceğini destekler niteliktedir.

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Cite This Article

Can, B., Kar, F., Kar, E., Özkoç, M., Şentürk, H., Dönmez, D. B., Kanbak, G., Alataş, İ. Ö., *, B. C. (2026). Biochemical and Histological Evaluation of The Impacts of Conivaptan and Boric Acid on Ischemia-induced Tissue Injury. Osmangazi Tıp Dergisi, Cilt: 48 Sayı: 4, 590–607. https://doi.org/10.20515/otd.1772344

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References (57)

  1. KDIGO clinical practice guideline for acute kidney injury. Chapter 21: definition and classification of AKI. Kidney Int, 2012; 2(Suppl 1): p. 19–22.
  2. Hoste, E.A.J., Kellum, J.A., Selby, N.M., Zarbock, A., Palevsky, P.M., Bagshaw, S.M., Goldstein, S.L., Cerdá, J., Chawla, L.S. Global epidemiology and outcomes of acute kidney injury. Nat Rev Nephrol, 2018. 14(10): p. 607–625.
  3. Ronco, C., Bellomo, R., Kellum, J.A. Acute kidney injury. Lancet, 2019. 394(10212): p. 1949–1964.
  4. Hoste, E.A., Bagshaw, S.M., Bellomo, R., Cely, C.M., Colman, R., Cruz, D.N., Edipidis, K., Forni L.G., Gomersall, C.D., Govil, D., Honoré, P.M., Joannes-Boyau, O., Joannidis, M., Korhonen, A.M., Lavrentieva, A., Mehta, R.L., Palevsky P., Roessler, E., Ronco, C., Uchino, S., Vazquez, J.A., Vidal Andrade, E., Webb, S., Kellum, J.A. Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study. Intensive Care Med, 2015. 41(8): p. 1411–1423.
  5. Li, N., Wang, Y., Wang, X., Sun, N., Gong, Y.H. Pathway network of pyroptosis and its potential inhibitors in acute kidney injury. Pharmacol Res, 2022. 175:106033.
  6. White, L.E., Hassoun, H.T. Inflammatory mechanisms of organ crosstalk during ischemic acute kidney injury. Int J Nephrol, 2012. 505197.
  7. Abogresha, N.M., Greish, S.M., Abdelaziz, E.Z., Khalil, W.F. Remote effect of kidney ischemia-reperfusion injury on pancreas: role of oxidative stress and mitochondrial apoptosis. Arch Med Sci, 2016. 12(2): p. 252–262.
  8. Jang, H.R., Rabb, H. Immune cells in experimental acute kidney injury. Nat Rev Nephrol, 2015. 11(2): p. 88–101.
  9. Yang, L., Besschetnova, T.Y., Brooks, C.R., Shah, J.V., Bonventre, J.V. Epithelial cell cycle arrest in G2/M mediates kidney fibrosis after injury. Nat Med, 2010. 16(5): p. 535–543.
  10. Fu, Y., Tang, C., Cai, J., Chen, G., Zhang, D., Dong, Z. Rodent models of AKI-CKD transition. Am J Physiol Renal Physiol, 2018. 315(4): F1098–F1106.
  11. Finn, W.F., Fernandez-Repollet, E., Goldfarb, D., Iaina, A., Eliahou, H.E. Attenuation of injury due to unilateral renal ischemia: delayed effects of contralateral nephrectomy. J Lab Clin Med, 1984. 103(2): p. 193–203.
  12. Owji, S.M., Nikeghbal, E., Moosavi, S.M. Comparison of ischaemia-reperfusion-induced acute kidney injury by clamping renal arteries, veins or pedicles in anaesthetized rats. Exp Physiol, 2018. 103(10): p. 1390–1402.
  13. Shiva, N., Sharma, N., Kulkarni, Y.A., Mulay, S.R., Gaikwad, A.B. Renal ischemia/reperfusion injury: an insight on in vitro and in vivo models. Life Sci, 2020; 256: 117860.
  14. Senturk, H., Kabay, S., Bayramoglu, G., Ozden, H., Yaylak, F., Yucel, M., Olgun, E.G., Kutlu, A. Silymarin attenuates the renal ischemia/reperfusion injury-induced morphological changes in the rat kidney. World J Urol, 2008. 26(4): p. 401–407.
  15. Can, B., Kar, F., Kar, E., Özkoç, M., Şentürk, H., Dönmez, D.B., Kanbak, G., Alataş, İ.Ö. Conivaptan and boric acid treatments in acute kidney injury: is this combination effective and safe?. Biol Trace Elem Res, 2022. 200(8): p. 3723–3737.
  16. Meijer, E., Boertien, W.E., Zietse, R., Gansevoort, R.T. Potential deleterious effects of vasopressin in chronic kidney disease and particularly autosomal dominant polycystic kidney disease. Kidney Blood Press Res, 2011. 34(4): p. 235–244.
  17. Moen, M.D., Keating, G.M. Intravenous conivaptan. Am J Cardiovasc Drugs, 2008. 8(5): p. 341–348.
  18. Palmer, B.F. Vasopressin receptor antagonists. Curr Hypertens Rep, 2015. 17(1): p. 510.
  19. Ferguson-Myrthil, N. Novel agents for the treatment of hyponatremia: a review of conivaptan and tolvaptan. Cardiol Rev, 2010. 18(6): p. 313–321.
  20. García-Arroyo, F.E., Tapia, E., Blas-Marron, M.G., Gonzaga, G., Silverio, O., Cristóbal, M., Osorio, H., Arellano-Buendía, A.S., Zazueta, C., Aparicio-Trejo, O.E., Reyes-García, J.G., Pedraza-Chaverri, J., Soto, V., Roncal-Jiménez, C., Johnson, R.J., Sánchez-Lozada, L.G. Vasopressin mediates the renal damage induced by limited fructose rehydration in recurrently dehydrated rats. Int J Biol Sci, 2017. 13(8): p. 961–975.
  21. Cabus, U., Secme, M., Kabukcu, C., Cil, N., Dodurga, Y., Mete, G., Fenkci, I.V. Boric acid as a promising agent in the treatment of ovarian cancer: molecular mechanisms. Gene, 2021. 796–797: 145799.
  22. Union of Turkish chambers of mechanical engineers and architects (UCTEA). (TMMOB in Turkish). The Boron Report. May, 2016. (http://www.tmmob.org.tr). ISBN: 978-605-01-0883-5.
  23. Colak, S., Geyikoglu, F., Keles, O.N., Türkez, H., Topal, A., Unal B. The neuroprotective role of boric acid on aluminum chloride-induced neurotoxicity. Toxicol Ind Health, 2011. 27(8): p. 700–710.
  24. Ince, S., Keles, H., Erdogan, M., Hazman, O., Kucukkurt, I. Protective effect of boric acid against carbon tetrachloride-induced hepatotoxicity in mice. Drug Chem Toxicol, 2012. 35(3): p. 285–292.
  25. Scorei, R., Ciubar, R., Ciofrangeanu, C.M., Mitran, V., Cimpean, A., Iordachescu, D. Comparative effects of boric acid and calcium fructoborate on breast cancer cells. Biol Trace Elem Res, 2008. 122(3): p. 197–205.
  26. Rajendran, K.G., Chen, S.Y., Sood, A., Spielvogel, B.F., Hall, I.H. The anti-osteoporotic activity of amine-carboxyboranes in rodents. Biomed Pharmacother, 1995. 49(3): p. 131–140.
  27. Chen, Z., Wu, H., Wang, H., Zaldivar-Silva, D., Agüero, L., Liu, Y., Zhang, Z., Yin, Y., Qiu, B., Zhao, J., Lu, X., Wang, S. An injectable anti-microbial and adhesive hydrogel for the effective noncompressible visceral hemostasis and wound repair. Mater Sci Eng C Mater Biol Appl, 2021. 129: 112422.
  28. Cetiner, E., Sayin, K., Tuzun, B., Ataseven, H. Could boron-containing compounds (BCCs) be effective against SARS-CoV-2 as anti-viral agent? Bratisl Lek Listy, 2021. 122(4): p. 263–269.
  29. Sogut, I., Oglakci, A., Kartkaya, K., Ol, K.K., Sogut, M.S., Kanbak, G., Inal, M.E. Effect of boric acid on oxidative stress in rats with fetal alcohol syndrome. Exp Ther Med, 2015. 9(3): p. 1023–1027.
  30. Ataizi, Z.S., Ozkoc, M., Kanbak, G., Karimkhani, H., Burukoglu Donmez, D., Ustunisik, N., Ozturk, B. Evaluation of the Neuroprotective Role of Boric Acid in Preventing Traumatic Brain Injury-Mediated Oxidative Stress. Turk Neurosurg, 2021. 31(4): p. 493-499.
  31. Hacioglu, C., Kar, F., Kacar, S., Sahinturk, V., Kanbak, G. High concentrations of boric acid trigger concentration-dependent oxidative stress, apoptotic pathways and morphological alterations in DU-145 human prostate cancer cell line. Biol Trace Elem Res, 2020. 193(2): p. 400–409.
  32. Karimkhani, H., Özkoç, M., Shojaolsadati, P., Uzuner, K., Donmez, D.B., Kanbak, G. Protective effect of boric acid and omega-3 on myocardial ınfarction in an experimental rat model. Biol Trace Elem Res, 2021. 199(7): p. 2612–2620.
  33. Özkoç, M., Can, B., Şentürk, H., Burukoğlu Dönmez, D., Kanbak, G. Possible curative effects of boric acid and bacillus clausii treatments on TNBS-ınduced ulcerative colitis in rats. Biol Trace Elem Res, 2023. 201(3): p. 1237–1251.
  34. İlhan, A.O, Can, B., Kar, F., Gündoğdu, A.Ç., Söğüt, İ., Kanbak, G. An investigation into the protective effects of various doses of boric acid on liver, kidney, and brain tissue damage caused by high levels of acute alcohol consumption Biol Trace Elem Res, 2023. 201(11): p. 5346–5357.
  35. Lopalco, A., Lopedota, A.A., Laquintana, V., Denora, N., Stella, V.J. Boric acid, a lewis acid with unique and unusual properties: formulation ımplications. J Pharm Sci, 2020. 109(8): p. 2375–2386.
  36. Karim, M., Boikess, R.S., Schwartz, R.A., Cohen, P.J. Dimethyl sulfoxide (DMSO): a solvent that may solve selected cutaneous clinical challenges. Arch Dermatol Res., 2023. 315(6): p. 1465-1472.
  37. Roldán-Fidalgo, A., Trinidad, A., Rodríguez-Valiente, A., García-Berrocal, J.R., Millán, I., Coronado, M.J., Ramírez-Camacho, R. Effect of intratympanic dimethyl sulphoxide (DMSO) in an in vivo model of cisplatin-related ototoxicity. Eur Arch Otorhinolaryngol, 2014. 271(12): p. 3121-6.
  38. Can, B., Oz, S., Sahinturk, V., Musmul, A., Alatas, İ.O. Effects of conivaptan versus mannitol on post-ischemic brain injury and edema. Eurasian J Med, 2019. 51(1): p. 42–48.
  39. Kar, F., Hacioglu, C., Senturk, H., Donmez, D.B., Kanbak G. The role of oxidative stress, renal ınflammation, and apoptosis in post ıschemic reperfusion ınjury of kidney tissue: the protective effect of dose-dependent boric acid administration. Biol Trace Elem Res, 2020. 195(1): p. 150–158.
  40. Bolukbas, C., Bolukbas, F.F., Horoz, M., Aslan, M., Celik, H., Erel, O. Increased oxidative stress associated with the severity of the liver disease in various forms of hepatitis B virus infection. BMC Infect Dis, 2005. 5:95.
  41. Azouz, A. A., Hersi, F., Ali, F. E. M., Hussein Elkelawy, A. M. M., Omar, H. A. Renoprotective effect of vinpocetine against ischemia/reperfusion injury: Modulation of NADPH oxidase/Nrf2, IKKβ/NF-κB p65, and cleaved caspase-3 expressions. Journal of biochemical and molecular toxicology, 2022. 36(7): e23046.
  42. Zhang, C., Sun, B., Wang, L., Korla, P. K., Liu, C. Micheliolide mitigates diabetic nephropathy by modulating oxidative stress and inflammation in rats. Phytomedicine: international journal of phytotherapy and phytopharmacology, 2025. 145: 157025.
  43. Raza, S. M., Mehmood, M. H., Mehdi, S., Saadullah, M., Faisal, M. N. Distachionate and Its Nanocomposites Modulate Oxidative Stress, Inflammation, and Diabetes-Related Genes in High-Fructose/Streptozotocin Model. ACS omega, 2025. 10(30): p. 33353–33370.
  44. Livak, K. J., Schmittgen, T. D. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods (San Diego, Calif.), 2001. 25(4): p. 402–408.
  45. Sahin, S., Burukoglu Donmez, D. Effects of Carnosine (Beta-Alanyl-L-Histidine) in an Experimental Rat Model of Acute Kidney Injury Due to Septic Shock. Medical science monitor: international medical journal of experimental and clinical research, 2018. 24: p. 305–316.
  46. Varga, G., Ghanem, S., Szabo, B., Nagy, K., Pal, N., Tanczos, B., Somogyi, V., Barath, B., Deak, A., Peto, K., Nemeth, N. Renal ischemia-reperfusion-induced metabolic and micro-rheological alterations and their modulation by remote organ ischemic preconditioning protocols in the rat. Clin Hemorheol Microcirc, 2019. 71(2): p. 225-236.
  47. Acar, M., Sayhan Kaplan, H., Erdem, A.F., Tomak, Y., Turan, G., Özdin, M. Effects of dexmedetomidine on new oxidative stress markers on renal ischaemia-reperfusion injury in rats: thiol/disulphide homeostasis and the ischaemia-modified albumin. Arch Physiol Biochem, 2022. 128(4): p. 1115–1120.
  48. Farrar, A. Acute kidney injury. The Nursing clinics of North America, 2018. 53(4): p. 499–510.
  49. Sluman, C., Gudka, P.M., McCormick, K. Acute kidney injury: pre-renal, intra-renal and post-renal. In: Braund R. editor. Renal medicine and clinical pharmacy. Advanced clinical pharmacy-research, development and practical applications, 2020. Vol. 1. Springer, Cham.
  50. Zuk, A., Bonventre, J.V. Acute kidney injury. Annu Rev Med, 2016. 67: p. 293–307.
  51. Domínguez Fernández, E., Siemers, F., Flohé, S., Nau, M., Schade, F.U. Effects of endotoxin tolerance on liver function after hepatic ischemia/reperfusion injury in the rat. Crit Care Med, 2002. 30(1): p. 165–170.
  52. Godet, C., Goujon J.M., Petit I., Lecron J.C., Hauet T., Mauco G., Carretier M., Robert, R. Endotoxin tolerance enhances interleukin-10 renal expression and decreases ischemia-reperfusion renal injury in rats. Shock (Augusta, Ga.), 2006. 25(4): p. 384–388.
  53. Kayama, F., Yoshida, T., Kodama, Y., Matsui, T., Matheson, J.M., Luster, M.I. Pro-inflammatory cytokines and interleukin 6 in the renal response to bacterial endotoxin. Cytokine, 1997. 9(9): p. 688–695.
  54. Deng, J., Kohda, Y., Chiao, H., Wang, Y., Hu, X., Hewitt, S.M., Miyaji, T., McLeroy, P., Nibhanupudy, B., Li, S., Star, R.A. Interleukin-10 inhibits ischemic and cisplatin-induced acute renal injury. Kidney Int, 2001. 60(6): p. 2118–2128.
  55. Nagpal, S., Patel, S., Jacobe, H., DiSepio, D., Ghosn, C., Malhotra, M., Teng, M., Duvic, M., Chandraratna, R.A. Tazarotene-induced gene 2 (TIG2), a novel retinoid-responsive gene in skin. J Invest Dermatol, 1997. 109(1): p. 91–95.
  56. Goralski, K.B., McCarthy, T.C., Hanniman, E.A., Zabel, B.A., Butcher, E.C., Parlee, S.D., Muruganandan, S., Sinal, C.J. Chemerin, a novel adipokine that regulates adipogenesis and adipocyte metabolism. J Biol Chem, 2007. 282(38): p. 28175–28188.
  57. Bonomini, M., Pandolfi, A. Chemerin in renal dysfunction and cardiovascular disease. Vascul Pharmacol, 2016. 77: p. 28–34.