Protective Effects of Humulus lupulus L. Extract on CCl₄-Induced Nephrotoxicity in Rats
DOI:
https://doi.org/10.61882/ijkd.20.02.8560Keywords:
Acute kidney injury, Carbon tetrachloride, Humulus lupulus, Nephrotoxicity, Oxidative stressAbstract
Introduction. Oxidative stress is a key contributor to acute kidney injury (AKI), a condition exacerbated by nephrotoxic agents like carbon tetrachloride (CCl₄). Humulus lupulus L. (hops), which is rich in polyphenols, exhibits potent antioxidant properties. This study evaluated the nephroprotective effects of Humulus lupulus L. extract on CCl₄-induced AKI in rats.
Methods. Twenty-four male Wistar rats were divided into four groups (n = 6): normal control, CCl₄ control, and two treatment groups receiving Humulus lupulus extract (100 or 200 mg/kg/day, intraperitoneally) for 14 days. On day 14, all groups except the normal control received CCl₄ (1 mL/kg, 1:1 v/v in olive oil, intraperitoneally). Forty-eight hours post-CCl₄ administration, serum and renal tissue samples were collected to assess biochemical markers (urea, creatinine, uric acid), oxidative stress parameters (malondialdehyde [MDA], total antioxidant capacity [TAC], catalase [CAT], superoxide dismutase [SOD], glutathione peroxidase [GPx]), and histopathological changes.
Results. CCl₄ significantly increased serum urea, creatinine, uric acid, and renal MDA levels while decreasing TAC, CAT, SOD, and GPx activities. Pretreatment with Humulus lupulus extract significantly attenuated these alterations, with the 200 mg/kg dose demonstrating superior efficacy. Histopathological analysis revealed reduced tubular and glomerular damage in treated groups.
Conclusion. Humulus lupulus extract attenuated CCl4-induced nephrotoxicity in rats by enhancing antioxidant defenses. These preclinical findings suggest that hops extract warrants further investigation as a potential candidate for mitigating oxidative stress in AKI.
Downloads
References
1. Pizzino G, Irrera N, Cucinotta M, Pallio G, Mannino F, Arcoraci V, et al. Oxidative Stress: Harms and Benefits for Human Health. Oxid Med Cell Longev. 2017;2017:8416763.
2. Dounousi E, Papavasiliou E, Makedou A, Ioannou K, Katopodis KP, Tselepis A, et al. Oxidative stress is progressively enhanced with advancing stages of CKD. Am J Kidney Dis. 2006;48(5):752-60.
3. Ishizaka Y, Yamakado M, Toda A, Tani M, Ishizaka N.Relationship between estimated glomerular filtration rate, albuminuria, and oxidant status in the Japanese population. BMC nephrology. 2013;14:191.
4. Ejaz AA, Kambhampati G, Ejaz NI, Dass B, Lapsia V, Arif AA, et al. Post-operative serum uric acid and acute kidney injury. J Nephrol. 2012;25(4):497-505.
5. Lameire NH, Bagga A, Cruz D, De Maeseneer J, Endre Z, Kellum JA, et al. Acute kidney injury: an increasing global concern. Lancet. 2013;382(9887):170-9.
6. Khwaja A. KDIGO clinical practice guidelines for acute kidney injury. Nephron Clinical practice. 2012;120(4):c179-84.
7. Zugravu CA, Bohiltea RE, Salmen T, Pogurschi E, Otelea MR. Antioxidants in Hops: Bioavailability, Health Effects and Perspectives for New Products. Antioxidants (Basel). 2022;11(2).
8. Hurth Z, Faber ML, Gendrisch F, Holzer M, Haarhaus B, Cawelius A, et al. The Anti-Inflammatory Effect of Humulus lupulus Extract In Vivo Depends on the Galenic System of the Topical Formulation. Pharmaceuticals (Basel, Switzerland). 2022;15(3).
9. Lin M, Xiang D, Chen X, Huo H. Role of Characteristic Components of Humulus lupulus in Promoting Human Health. Journal of agricultural and food chemistry.
2019;67(30):8291-302.
10. Karabín M, Hudcová T, Jelínek L, Dostálek P. Biologically Active Compounds from Hops and Prospects for Their Use. Comprehensive reviews in food science and food safety. 2016;15(3):542-67.
11. Bland JS, Minich D, Lerman R, Darland G, Lamb J, Tripp M, et al. Isohumulones from hops (Humulus lupulus) and their potential role in medical nutrition therapy. PharmaNutrition. 2015;3(2):46-52.
12. Abram V, Čeh B, Vidmar M, Hercezi M, Lazić N, Bucik V, et al. A comparison of antioxidant and antimicrobial activity between hop leaves and hop cones. Industrial Crops and Products. 2015;64:124-34.
13. Li Y, Yao J, Han C, Yang J, Chaudhry MT, Wang S, et al. Quercetin, Inflammation and Immunity. Nutrients. 2016;8(3):167.
14. Darband SG, Kaviani M, Yousefi B, Sadighparvar S, Pakdel FG, Attari JA, et al. Quercetin: A functional dietary flavonoid with potential chemo-preventive properties
in colorectal cancer. Journal of cellular physiology. 2018;233(9):6544-60.
15. Liu M, Hansen PE, Wang G, Qiu L, Dong J, Yin H, et al. Pharmacological profile of xanthohumol, a prenylated flavonoid from hops (Humulus lupulus). Molecules (Basel, Switzerland). 2015;20(1):754-79.
16. Jaramillo-Juarez F, Rodriguez-Vazquez ML, Rincon-Sanchez AR, Consolacion Martinez M, Ortiz GG, Llamas J, et al. Acute renal failure induced by carbon tetrachloride in rats with hepatic cirrhosis. Ann Hepatol. 2008;7(4):331-8.
17. Fouladi H, Rezagholizadeh L, Ojarudi M, Khalafi A, Mazani M, • Mahdavifard S. The Effect of Humulus lupulus Extract on Serum Biochemical Parameters in Carbon Tetrachloride-induced Hepatotoxicity in Rats. Journal of Ardabil University of Medical Sciences.
2020;20(3):352-60.
18. Ojarudi M, Golchin A, Karamdel HR, Valilo M, Ranjbarvan P. Protective effects of Elaeagnus angustifolia L. fruit extract on CCl4-induced oxidative stress and inflammation in rats liver. Avicenna Journal of Phytomedicine. 2025.
19. Rezagholizadeh L, Ojarudi M, Moradi A, Salimnejad
R, Khonakdar-Tarsi A, Matin S, et al. Protective effects of Cinnamomum zeylanicum and Zingiber officinale extract against CCl4-induced acute kidney injury in rats. Physiology and Pharmacology. 2022;26(2):158-67.
20. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976;72:248-54.
21. Benzie IF, Strain JJ. The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power”: the FRAP assay. Anal Biochem. 1996;239(1):70-6.
22. Mihara M, Uchiyama M. Determination of malonaldehyde precursor in tissues by thiobarbituric acid test. Anal Biochem. 1978;86(1):271-8.
23. Aebi H. Catalase in vitro. Methods Enzymol.
1984;105:121-6.
24. Ramesh G, Reeves WB. TNF-α mediates chemokine and cytokine expression and renal injury in cisplatin nephrotoxicity. The Journal of Clinical Investigation. 2002;110(6):835-42.
25. Makris D, Mertens PR, Dounousi E, Giamouzis G, Nseir
S. Editorial: Oxidative Stress in the Critically Ill Patients: Pathophysiology and Potential Interventions. Oxid Med Cell Longev. 2018;2018:2353128.
26. Sahreen S, Khan MR, Khan RA, Alkreathy HM. Protective effects of Carissa opaca fruits against CCl4-induced oxidative kidney lipid peroxidation and trauma in rat. Food Nutr Res. 2015;59:28438.
27. Ekpo GI. Quercetin and hesperidin protection against hepato-renal damage occasioned by carbon tetrachloride (CCL4) in a rat model. Pharmacological Research -Modern Chinese Medicine. 2024.
28. El-Haskoury R, Al-Waili N, Kamoun Z, Makni M, Al-Waili H, Lyoussi B. Antioxidant Activity and Protective Effect of Carob Honey in CCl(4)-induced Kidney and Liver Injury. Arch Med Res. 2018;49(5):306-13.
29. Radulovic NS, Randjelovic PJ, Stojanovic NM, Ilic IR, Miltojevic AB, Stojkovic MB, et al. Effect of two esters of N-methylanthranilic acid from Rutaceae species on impaired kidney morphology and function in rats caused by CCl4. Life Sci. 2015;135:110-7.
30. El-Haskoury R, Al-Waili N, Kamoun Z, Makni M, Al-Waili A, Lyoussi B. Antioxidant activity and protective effect of propolis against carbon tetrachloride-induced liver and kidney injury by modulation of oxidative parameters. Vet World. 2021;14(12):3076-83.
31. Elsawy H, Badr GM, Sedky A, Abdallah BM, Alzahrani AM, Abdel-Moneim AM. Rutin ameliorates carbon tetrachloride (CCl(4))-induced hepatorenal toxicity and hypogonadism in male rats. PeerJ. 2019;7:e7011.
32. Bartosz G. Total antioxidant capacity. Adv Clin Chem. 2003;37:219-92.
33. Bahamonde S, Dialektopoulos K, Escamilla-Rivera
C, Farrugia G, Gakis V, Hendry M, et al. Teleparallel gravity: from theory to cosmology. Reports on Progress in Physics. 2022.
34. Mazani M, Rezagholizadeh L, Shamsi S, Mahdavifard S, Ojarudi M, Salimnejad R, et al. Protection of CCl(4)-induced hepatic and renal damage by linalool. Drug Chem Toxicol. 2022;45(3):963-71.
35. Rezagholizadeh L. Protective effects of Cinnamomum zeylanicum and Zingiber officinale extract against CCl4-induced acute kidney injury in rats. Physiology and Pharmacology. 2022.
36. Sun S, Wang X, Yuan A, Liu J, Li Z, Xie D, et al. Chemical constituents and bioactivities of hops (Humulus lupulus L.) and their effects on beer-related microorganisms. Food and Energy Security. 2022;11(2):e367.
Downloads
Published
Data Availability Statement
The data used in this study are not publicly available. However, the data are available from the corresponding author, Aliakbar Fazaeli, upon reasonable request.
