Histopathological and Antioxidant Effects of Bromelain on Kidney Tissue of Tyloxapol-Induced Hyperlipidemic Rats
Yıl 2024,
Cilt: 29 Sayı: 2, 413 - 422, 31.08.2024
Ayşe Nurseli Sulumer
,
Esra Palabıyık
,
Bahri Avcı
,
Handan Uğuz
,
Hakan Aşkın
Öz
This study was designed to investigate the nephroprotective effect of Bromelain against oxidative stress induced by Tyloxopol-induced hyperlipidemia in rats. Rats (n=6) were divided into three groups. I: Control (C) Group: No treatment was given and only distilled water was given; II: Tyloxapol (TX) Group: Group receiving Tyloxapol (400 mg/kg, i.p); III: Tyloxapol + Bromelain (TX+BR) Group: Group receiving Tyloxapol (400 mg/kg, i.p.) and group receiving Bromelain (250 mg/kg, o.d.) for 18 days. As a result of Tyloxapol administration, oxidative stress parameters SOD and CAT levels decreased, while MDA levels increased. In addition, histopathologic variations were detected in kidney sections. On the other hand, lipid peroxidation decreased and most of the studied parameters improved with combined administration (TX+BR group). According to the results obtained, bromelain may be a potent and alternative agent with protective effect for further studies.
Etik Beyan
Ethics committee approval was received for this study from Atatürk University Medical Experimental Application and Research Center (ATADEM) (dated 15.11.2021 and E-55885869-900-2100312890).
Teşekkür
We would like to thank Atatürk University Faculty of Science Molecular Biology/Genetics Departments for their support of our experimental study.
Kaynakça
- Akaras, N., Toktay, E., Celep, N. A., Yüce, N., Şimşek, H., & Özkan, H. İ. (2023). Antioxidant effects of bromelain on paracetamol-induced renal injury in rats. Archives of Basic Clinical Research, 5, 364-371. https://doi.org/10.5152/ABCR.2023.22123
- Akinmoladun, A. C., Adegbamigbe, A. D., Okafor, N. R., Josiah, S. S., & Olaleye, M. T. (2021). Toxicological and pharmacological assessment of a multi herbal phytopharmaceutical on Triton X-1339-induced hyperlipidemia and allied biochemical dysfunctions. Journal of Food Biochemistry, 45(3), e13238. https://doi.org/10.1111/jfbc.13238
- Alissa, E. M., & Ferns, G. A. (2017). Dietary fruits and vegetables and cardiovascular diseases risk. Critical Reviews in Food Science and Nutrition, 57(9), 1950-1962. https://doi.org/10.1080/10408398.2015.1040487
- Allawadhi, P., Khurana, A., Sayed, N., Kumari, P., & Godugu, C. (2018). Isoproterenol‐induced cardiac ischemia and fibrosis: Plant‐based approaches for intervention. Phytotherapy Research, 32(10), 1908-1932. https://doi.org/10.1002/ptr.6152
- Baldissera, M. D., Souza, C. F., Grando, T. H., Doleski, P. H., Boligon, A. A., Stefani, L. M., & Monteiro, S. G. (2017). Hypolipidemic effect of β-caryophyllene to treat hyperlipidemicrats. Naunyn-Schmiedeberg's Archives of Pharmacology, 390(2), 215-223. https://doi.org/10.1007/s00210-016-1326-3
- Chukwuebuka, N. B., Elias, D. T. M., Ijego, A. E., Peggy, O. E., Ejime, A. C., & Omeru, O. (2021). Changes in antioxidant enzymes activities and lipid peroxidase level in tissues of stress-induced rats. Biomedical and Pharmacology Journal, 14(2), 583-596. https://dx.doi.org/10.13005/bpj/2161
- Colletti, A., Li, S., Marengo, M., Adinolfi, S., & Cravotto, G. (2021). Recent advances and insights into bromelain processing, pharmacokinetics and therapeutic uses. Applied Sciences, 11(18), 8428. https://doi.org/10.3390/app11188428
- Çakmak, Ö. (2020). The effects of boric acid on renal ischemia/reperfusion injury in rat. (MSc), Atatürk Üniversitesi, Fen Bilimleri Enstitüsü, Erzurum, Türkiye.
- deSousa, J. A., Pereira, P., Allgayer, M. D. C., Marroni, N. P., de Barros Falcão Ferraz, A., & Picada, J. N. (2017). Evaluation of DNA damage in Wistar rat tissues with hyperlipidemia induced by tyloxapol. Experimental and Molecular Pathology, 103(1), 51–55. https://doi.org/10.1016/j.yexmp.2017.06.009
- Dudhipala, N. R., Ettireddy, S. R., & Puchakayala, G. R. (2021). Attenuation of lipid levels in triton induced hyperlipidemia rats through rosuvastatin calcium nanoparticles: Pharmacokinetic and pharmacodynamic studies. Chemistry and Physics of Lipids, 237, 105081. https://doi.org/10.1016/j.chemphyslip.2021.105081
- El-Demerdash, F. M., Baghdadi, H. H., Ghanem, N. F., & Al Mhanna, A. B. (2020). Nephroprotective role of bromelain against oxidative injury induced by aluminum in rats. Environmental Toxicologyand Pharmacology, 80, 103509. https://doi.org/10.1016/j.etap.2020.103509
- Feng, Y., Gao, S., Zhu, T., Sun, G., Zhang, P., Huang, Y., Qu, S., Du, X., & Mou, D. (2022). Hawthorn fruit acid consumption attenuate shyperlipidemia-associated oxidative damage in rats. Frontiers in Nutrition, 9, 936229. https://doi.org/10.3389/fnut.2022.936229
- Fidèle, N., Joseph, B., Emmanuel, T., & Théophile, D. (2017). Hypolipidemic, antioxidantand anti-atherosclerogenic effect of aqueous extract leaves of Cassia. Occidentalis Linn (Caesalpiniaceae) in diet-induced hypercholesterolemic rats. BMC Complementary and Alternative Medicine, 17(1), 76. https://doi.org/10.1186/s12906-017-1566-x
- Gai, Z., Wang, T., Visentin, M., Kullak-Ublick, G. A., Fu, X., & Wang, Z. (2019). Lipid accumulation and chronic kidney disease. Nutrients, 11(4), 722. https://doi.org/10.3390/nu11040722
- Gara, A. B., Kolsi, R. B. A., Chaaben, R., Hammami, N., Kammoun, M., Patti, F. P., ... & Belghith, K. (2017). Inhibition of key digestive enzymes related to hyperlipidemia and protection of liver-kidney functions by Cystoseira crinita sulphated polysaccharide in high-fat diet-fed rats. Biomedicine & Pharmacotherapy, 85, 517-526. https://doi.org/10.1016/j.biopha.2016.11.059
- Gaschler, M. M., & Stockwell, B. R. (2017). Lipid peroxidation in celldeath. Biochemical and Biophysical Research Communications, 482(3), 419-425. https://doi.org/10.1016/j.bbrc.2016.10.086
- Gürel, A., & Kaya, K. (2022). Bromelain has antioxidant effect on methotrexate hepatotoxicity and nephrotoxicity. Van Sağlık Bilimleri Dergisi, 15(1), 37-42. https://doi.org/10.52976/vansaglik.982411
- Hikisz, P., & Bernasinska-Slomczewska, J. (2021). Beneficial properties of Bromelain. Nutrients, 13(12), 4313. https://doi.org/10.3390/nu13124313
- Husain, M. J., Spencer, G., Nugent, R., Kostova, D., & Richter, P. (2022). The cost-effectiveness of hyperlipidemia medication in low- and middle-income countries: a review. Global Heart, 17(1), 18. https://doi.org/10.5334/gh.1097
- Iyer, D., & Patil, U. K. (2019). Assessment of Antihyperlipidemic and Antitumor effect of isolated active Phytoconstituents from Apium graveolens L. through Bioassay-Guided procedures. Journal of Dietary Supplements, 16(2), 193-206. https://doi.org/10.1080/19390211.2018.1448921
- Kalaiselvi, M., Gomathi, D., Ravikumar, G., Devaki, K., & Uma, C. (2013). Ameliorative effect of Ananus comosus peel on 7, 12 dimethylbenz (α) anthracene induced mammary carcinogenesis with reference tooxidative stress. Journal of Acute Disease, 2(1), 22-28. https://doi.org/10.1016/S2221-6189(13)60089-X
- Karale, P., Dhawale, S., & Karale, M. (2022). HR-LCMS analysis and Antihyperlipidemic effect of Ethanolic Leaf extract of Momordica charantia L. Hacettepe University Journal of the Faculty of Pharmacy, 42(2), 93-104. https://doi.org/10.52794/hujpharm.1063583
- Li, Y., Gong, W., Liu, J., Chen, X., Suo, Y., Yang, H., & Gao, X. (2022). Angiopoietin-like protein 4 promotes hyperlipidemia-induced renal injurybydown-regulatingtheexpression of ACTN4. Biochemical and Biophysical Research Communications, 595, 69-75. https://doi.org/10.1016/j.bbrc.2022.01.061
- Liu, Y., Sun, Y., Xue, B. H., Wang, X. D., & Yu, W. L. (2021). Negative regulation of SIRT1 by IRF9 ınvolved in Hyperlipidemia acute Pancreatitis associated with Kidney ınjury. Digestive Diseases and Sciences, 66(4), 1063-1071. https://doi.org/10.1007/s10620-020-06331-1
- Manzoni, A. G., Passos, D. F., Leitemperger, J. W., Storck, T. R., Doleski, P. H., Jantsch, M. H., ... & Leal, D. B. (2020). Hyperlipidemia-induced lipotoxicity and immune activation in rats are prevented by curcumin and rutin. International Immunopharmacology, 81, 106217. https://doi.org/10.1016/j.intimp.2020.106217
- Nwozo, S. O., Lewis, Y. T., & Oyinloye, B. E. (2017). The effects of Piper Guineense versus Sesamum Indicum Aqueous extracts on Lipid metabolism and antioxidants in hypercholesterolemic rats. Iranian Journal of Medical Sciences, 42(5), 449-456.
- Palabiyik, E., Sulumer, A. N., Uguz, H., Avci, B., Askin, S., & Askin, H. (2023). Walnut fruit diaphragm ethanol extract ameliorates damage due to Triton WR‐1339‐induced hyperlipidemia in rats. European Journal of Lipid Science and Technology, 2300105. https://doi.org/10.1002/ejlt.202300105
- Parwin, A., Najmi, A. K., Ismail, M. V., Kaundal, M., & Akhtar, M. (2019). Protective effects of alendronate in Triton X-100-induced hyperlipidemia in rats. The Turkish Journal of Gastroenterology, 30(6), 557-564. https://doi.org/10.5152/tjg.2019.18076
- Singh, R. P., & Pattnaik, A. K. (2024). Scientific insights into Hyperlipidemia Mitigation: a profound examination of ısolated bioactive fractions of Kalanchoe pinnata (Lam.) leaves and their therapeutic implications using In Vitro, In Vivo, and In Silico study from the characterized compounds using HPTLC MS/MSn analysis. Pharmacognosy Magazine, (online first). https://doi.org/10.1177/09731296241228925
- Sulumer, A. N., Palabıyık, E., Avcı, B., Uguz, H., Demir, Y., Serhat Özaslan, M., & Aşkın, H. (2023). Protective effect of bromelain on some metabolic enzyme activities in tyloxapol‐induced hyperlipidemic rats. Biotechnology and Applied Biochemistry. https://doi.org/10.1002/bab.2517
- Toth, P. P., & Banach, M. (2019). Statins: then and now. Methodist DeBakey cardiovascular journal, 15(1), 23-31. https://doi.org/10.14797/mdcj-15-1-23
Tyloxapol ile İndüklenmiş Hiperlipidemik Sıçanların Böbrek Dokusu Üzerinde Bromelainin Histopatolojik ve Antioksidan Etkileri
Yıl 2024,
Cilt: 29 Sayı: 2, 413 - 422, 31.08.2024
Ayşe Nurseli Sulumer
,
Esra Palabıyık
,
Bahri Avcı
,
Handan Uğuz
,
Hakan Aşkın
Öz
Bu çalışma, ratlarda Tyloxopol ile indüklenen hiperlipidemi neticesinde oluşan oksidatif strese karşı Bromelain’in nefroprotektif etkisinin incelenmesi için tasarlandı. Ratlar (n=6) üç grup altında sınıflandırıldı. I: Kontrol (C) Grubu: Herhangi bir uygulama yapılmayan ve sadece distile su verilen grup; II: Tyloxapol (TX) Grup: Tylaxopol (400 mg/kg, i.p) alan grup; III: Tyloxapol + Bromelain (TX+BR) Grup: Tylaxopol (400 mg/kg, i.p) alan ve 18 gün Bromelain (250 mg/kg, o.d.) alan grup. Tyloxapol uygulaması neticesinde oksidatif stres parametrelerinden SOD ve CAT seviyelerinde azalma meydana gelirken MDA seviyelerinde artış görüldü. Buna ek olarak böbrek kesitlerinde histopatolojik varyasyonlar tespit edildi. Bunun aksine çalışmada, kombine uygulama ile (TX+BR grubu) lipid peroksidasyonu azaldı ve çalışılan parametrelerin çoğunda iyileşme görüldü. Elde edilen sonuçlara göre bromelain’in daha sonraki çalışmalar için koruyucu etkiye sahip güçlü ve alternatif bir ajan olabileceği düşünülmektedir.
Etik Beyan
Bu çalışma için Atatürk Üniversitesi Tıbbi Deneysel Uygulama ve Araştırma Merkezi'nden (ATADEM) (15.11.2021 tarih ve E-55885869-900-2100312890) etik kurul onayı alındı.
Teşekkür
Deneysel çalışmamıza desteklerinden dolayı Atatürk Üniversitesi Fen Fakültesi Moleküler Biyoloji/Genetik Bölümlerine teşekkür ederiz.
Kaynakça
- Akaras, N., Toktay, E., Celep, N. A., Yüce, N., Şimşek, H., & Özkan, H. İ. (2023). Antioxidant effects of bromelain on paracetamol-induced renal injury in rats. Archives of Basic Clinical Research, 5, 364-371. https://doi.org/10.5152/ABCR.2023.22123
- Akinmoladun, A. C., Adegbamigbe, A. D., Okafor, N. R., Josiah, S. S., & Olaleye, M. T. (2021). Toxicological and pharmacological assessment of a multi herbal phytopharmaceutical on Triton X-1339-induced hyperlipidemia and allied biochemical dysfunctions. Journal of Food Biochemistry, 45(3), e13238. https://doi.org/10.1111/jfbc.13238
- Alissa, E. M., & Ferns, G. A. (2017). Dietary fruits and vegetables and cardiovascular diseases risk. Critical Reviews in Food Science and Nutrition, 57(9), 1950-1962. https://doi.org/10.1080/10408398.2015.1040487
- Allawadhi, P., Khurana, A., Sayed, N., Kumari, P., & Godugu, C. (2018). Isoproterenol‐induced cardiac ischemia and fibrosis: Plant‐based approaches for intervention. Phytotherapy Research, 32(10), 1908-1932. https://doi.org/10.1002/ptr.6152
- Baldissera, M. D., Souza, C. F., Grando, T. H., Doleski, P. H., Boligon, A. A., Stefani, L. M., & Monteiro, S. G. (2017). Hypolipidemic effect of β-caryophyllene to treat hyperlipidemicrats. Naunyn-Schmiedeberg's Archives of Pharmacology, 390(2), 215-223. https://doi.org/10.1007/s00210-016-1326-3
- Chukwuebuka, N. B., Elias, D. T. M., Ijego, A. E., Peggy, O. E., Ejime, A. C., & Omeru, O. (2021). Changes in antioxidant enzymes activities and lipid peroxidase level in tissues of stress-induced rats. Biomedical and Pharmacology Journal, 14(2), 583-596. https://dx.doi.org/10.13005/bpj/2161
- Colletti, A., Li, S., Marengo, M., Adinolfi, S., & Cravotto, G. (2021). Recent advances and insights into bromelain processing, pharmacokinetics and therapeutic uses. Applied Sciences, 11(18), 8428. https://doi.org/10.3390/app11188428
- Çakmak, Ö. (2020). The effects of boric acid on renal ischemia/reperfusion injury in rat. (MSc), Atatürk Üniversitesi, Fen Bilimleri Enstitüsü, Erzurum, Türkiye.
- deSousa, J. A., Pereira, P., Allgayer, M. D. C., Marroni, N. P., de Barros Falcão Ferraz, A., & Picada, J. N. (2017). Evaluation of DNA damage in Wistar rat tissues with hyperlipidemia induced by tyloxapol. Experimental and Molecular Pathology, 103(1), 51–55. https://doi.org/10.1016/j.yexmp.2017.06.009
- Dudhipala, N. R., Ettireddy, S. R., & Puchakayala, G. R. (2021). Attenuation of lipid levels in triton induced hyperlipidemia rats through rosuvastatin calcium nanoparticles: Pharmacokinetic and pharmacodynamic studies. Chemistry and Physics of Lipids, 237, 105081. https://doi.org/10.1016/j.chemphyslip.2021.105081
- El-Demerdash, F. M., Baghdadi, H. H., Ghanem, N. F., & Al Mhanna, A. B. (2020). Nephroprotective role of bromelain against oxidative injury induced by aluminum in rats. Environmental Toxicologyand Pharmacology, 80, 103509. https://doi.org/10.1016/j.etap.2020.103509
- Feng, Y., Gao, S., Zhu, T., Sun, G., Zhang, P., Huang, Y., Qu, S., Du, X., & Mou, D. (2022). Hawthorn fruit acid consumption attenuate shyperlipidemia-associated oxidative damage in rats. Frontiers in Nutrition, 9, 936229. https://doi.org/10.3389/fnut.2022.936229
- Fidèle, N., Joseph, B., Emmanuel, T., & Théophile, D. (2017). Hypolipidemic, antioxidantand anti-atherosclerogenic effect of aqueous extract leaves of Cassia. Occidentalis Linn (Caesalpiniaceae) in diet-induced hypercholesterolemic rats. BMC Complementary and Alternative Medicine, 17(1), 76. https://doi.org/10.1186/s12906-017-1566-x
- Gai, Z., Wang, T., Visentin, M., Kullak-Ublick, G. A., Fu, X., & Wang, Z. (2019). Lipid accumulation and chronic kidney disease. Nutrients, 11(4), 722. https://doi.org/10.3390/nu11040722
- Gara, A. B., Kolsi, R. B. A., Chaaben, R., Hammami, N., Kammoun, M., Patti, F. P., ... & Belghith, K. (2017). Inhibition of key digestive enzymes related to hyperlipidemia and protection of liver-kidney functions by Cystoseira crinita sulphated polysaccharide in high-fat diet-fed rats. Biomedicine & Pharmacotherapy, 85, 517-526. https://doi.org/10.1016/j.biopha.2016.11.059
- Gaschler, M. M., & Stockwell, B. R. (2017). Lipid peroxidation in celldeath. Biochemical and Biophysical Research Communications, 482(3), 419-425. https://doi.org/10.1016/j.bbrc.2016.10.086
- Gürel, A., & Kaya, K. (2022). Bromelain has antioxidant effect on methotrexate hepatotoxicity and nephrotoxicity. Van Sağlık Bilimleri Dergisi, 15(1), 37-42. https://doi.org/10.52976/vansaglik.982411
- Hikisz, P., & Bernasinska-Slomczewska, J. (2021). Beneficial properties of Bromelain. Nutrients, 13(12), 4313. https://doi.org/10.3390/nu13124313
- Husain, M. J., Spencer, G., Nugent, R., Kostova, D., & Richter, P. (2022). The cost-effectiveness of hyperlipidemia medication in low- and middle-income countries: a review. Global Heart, 17(1), 18. https://doi.org/10.5334/gh.1097
- Iyer, D., & Patil, U. K. (2019). Assessment of Antihyperlipidemic and Antitumor effect of isolated active Phytoconstituents from Apium graveolens L. through Bioassay-Guided procedures. Journal of Dietary Supplements, 16(2), 193-206. https://doi.org/10.1080/19390211.2018.1448921
- Kalaiselvi, M., Gomathi, D., Ravikumar, G., Devaki, K., & Uma, C. (2013). Ameliorative effect of Ananus comosus peel on 7, 12 dimethylbenz (α) anthracene induced mammary carcinogenesis with reference tooxidative stress. Journal of Acute Disease, 2(1), 22-28. https://doi.org/10.1016/S2221-6189(13)60089-X
- Karale, P., Dhawale, S., & Karale, M. (2022). HR-LCMS analysis and Antihyperlipidemic effect of Ethanolic Leaf extract of Momordica charantia L. Hacettepe University Journal of the Faculty of Pharmacy, 42(2), 93-104. https://doi.org/10.52794/hujpharm.1063583
- Li, Y., Gong, W., Liu, J., Chen, X., Suo, Y., Yang, H., & Gao, X. (2022). Angiopoietin-like protein 4 promotes hyperlipidemia-induced renal injurybydown-regulatingtheexpression of ACTN4. Biochemical and Biophysical Research Communications, 595, 69-75. https://doi.org/10.1016/j.bbrc.2022.01.061
- Liu, Y., Sun, Y., Xue, B. H., Wang, X. D., & Yu, W. L. (2021). Negative regulation of SIRT1 by IRF9 ınvolved in Hyperlipidemia acute Pancreatitis associated with Kidney ınjury. Digestive Diseases and Sciences, 66(4), 1063-1071. https://doi.org/10.1007/s10620-020-06331-1
- Manzoni, A. G., Passos, D. F., Leitemperger, J. W., Storck, T. R., Doleski, P. H., Jantsch, M. H., ... & Leal, D. B. (2020). Hyperlipidemia-induced lipotoxicity and immune activation in rats are prevented by curcumin and rutin. International Immunopharmacology, 81, 106217. https://doi.org/10.1016/j.intimp.2020.106217
- Nwozo, S. O., Lewis, Y. T., & Oyinloye, B. E. (2017). The effects of Piper Guineense versus Sesamum Indicum Aqueous extracts on Lipid metabolism and antioxidants in hypercholesterolemic rats. Iranian Journal of Medical Sciences, 42(5), 449-456.
- Palabiyik, E., Sulumer, A. N., Uguz, H., Avci, B., Askin, S., & Askin, H. (2023). Walnut fruit diaphragm ethanol extract ameliorates damage due to Triton WR‐1339‐induced hyperlipidemia in rats. European Journal of Lipid Science and Technology, 2300105. https://doi.org/10.1002/ejlt.202300105
- Parwin, A., Najmi, A. K., Ismail, M. V., Kaundal, M., & Akhtar, M. (2019). Protective effects of alendronate in Triton X-100-induced hyperlipidemia in rats. The Turkish Journal of Gastroenterology, 30(6), 557-564. https://doi.org/10.5152/tjg.2019.18076
- Singh, R. P., & Pattnaik, A. K. (2024). Scientific insights into Hyperlipidemia Mitigation: a profound examination of ısolated bioactive fractions of Kalanchoe pinnata (Lam.) leaves and their therapeutic implications using In Vitro, In Vivo, and In Silico study from the characterized compounds using HPTLC MS/MSn analysis. Pharmacognosy Magazine, (online first). https://doi.org/10.1177/09731296241228925
- Sulumer, A. N., Palabıyık, E., Avcı, B., Uguz, H., Demir, Y., Serhat Özaslan, M., & Aşkın, H. (2023). Protective effect of bromelain on some metabolic enzyme activities in tyloxapol‐induced hyperlipidemic rats. Biotechnology and Applied Biochemistry. https://doi.org/10.1002/bab.2517
- Toth, P. P., & Banach, M. (2019). Statins: then and now. Methodist DeBakey cardiovascular journal, 15(1), 23-31. https://doi.org/10.14797/mdcj-15-1-23