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Olea europaea leaf extract up-regulates Nrf2/ARE/HO-1 signaling and attenuates cyclophosphamide-induced oxidative stress, inflammation and apoptosis in rat kidney.
Biomed Pharmacother. 2019 Mar; 111:676-685.BP

Abstract

Olive leaf extract (OLE) has potential health benefits and protects against cytotoxicity in different organs. However, nothing has yet been reported on its potential to prevent cyclophosphamide (CP)-induced nephrotoxicity. This study investigated the possible protective effect of OLE on CP-induced kidney injury in rats, focusing on oxidative stress, inflammation, apoptosis and Nrf2/ARE/HO-1 signaling. Rats received 100 or 200 mg/kg body weight OLE for 15 days and a single injection of 150 mg/kg CP at day 16. CP induced kidney injury evidenced by the significantly increased serum creatinine and urea, and histopathological alterations, including glomerular atrophy, interstitial hemorrhage, dilated urinary space and necrosis. CP-induced rats exhibited increased kidney lipid peroxidation, protein carbonyl, nitric oxide (NO) and pro-inflammatory cytokines, and up-regulated NF-κB, Bax, cytochrome c and caspase-3. OLE ameliorated kidney function markers and prevented CP-induced tissue damage. In addition, OLE significantly prevented oxidative stress, inflammation and apoptosis by enhancing the antioxidant defenses and Bcl-2 expression, and suppressing the pro-inflammatory and pro-apoptotic markers NF-κB, Bax, cytochrome c and caspase-3. OLE up-regulated Nrf2, HO-1 and NQO-1 expression in the kidney of CP-induced rats. In conclusion, OLE has a substantial protective role against CP-induced nephrotoxicity in rats by up-regulating the Nrf2/ARE/HO-1 signaling, enhancing the antioxidant activity and attenuating inflammation and apoptosis.

Authors+Show Affiliations

Biology Department, College of Science, Jouf University, Saudi Arabia.Physiology Department, College of Medicine, King Saud University, Saudi Arabia.Department of Biology, College of Science, Princess Nourah bint Abdulrahman University, Saudi Arabia.Biology Department, College of Science, Jouf University, Saudi Arabia.Physiology Division, Zoology Department, Faculty of Science, Beni-Suef University, Egypt. Electronic address: ayman.mahmoud@science.bsu.edu.eg.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30611992

Citation

ALHaithloul, Haifa A S., et al. "Olea Europaea Leaf Extract Up-regulates Nrf2/ARE/HO-1 Signaling and Attenuates Cyclophosphamide-induced Oxidative Stress, Inflammation and Apoptosis in Rat Kidney." Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, vol. 111, 2019, pp. 676-685.
ALHaithloul HAS, Alotaibi MF, Bin-Jumah M, et al. Olea europaea leaf extract up-regulates Nrf2/ARE/HO-1 signaling and attenuates cyclophosphamide-induced oxidative stress, inflammation and apoptosis in rat kidney. Biomed Pharmacother. 2019;111:676-685.
ALHaithloul, H. A. S., Alotaibi, M. F., Bin-Jumah, M., Elgebaly, H., & Mahmoud, A. M. (2019). Olea europaea leaf extract up-regulates Nrf2/ARE/HO-1 signaling and attenuates cyclophosphamide-induced oxidative stress, inflammation and apoptosis in rat kidney. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 111, 676-685. https://doi.org/10.1016/j.biopha.2018.12.112
ALHaithloul HAS, et al. Olea Europaea Leaf Extract Up-regulates Nrf2/ARE/HO-1 Signaling and Attenuates Cyclophosphamide-induced Oxidative Stress, Inflammation and Apoptosis in Rat Kidney. Biomed Pharmacother. 2019;111:676-685. PubMed PMID: 30611992.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Olea europaea leaf extract up-regulates Nrf2/ARE/HO-1 signaling and attenuates cyclophosphamide-induced oxidative stress, inflammation and apoptosis in rat kidney. AU - ALHaithloul,Haifa A S, AU - Alotaibi,Mohammed F, AU - Bin-Jumah,May, AU - Elgebaly,Hassan, AU - Mahmoud,Ayman M, Y1 - 2019/01/03/ PY - 2018/10/13/received PY - 2018/12/15/revised PY - 2018/12/29/accepted PY - 2019/1/7/pubmed PY - 2019/6/14/medline PY - 2019/1/7/entrez KW - Acrolein KW - Apoptosis KW - Cyclophosphamide KW - Nephrotoxicity KW - Olive leaf KW - Oxidative stress SP - 676 EP - 685 JF - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JO - Biomed Pharmacother VL - 111 N2 - Olive leaf extract (OLE) has potential health benefits and protects against cytotoxicity in different organs. However, nothing has yet been reported on its potential to prevent cyclophosphamide (CP)-induced nephrotoxicity. This study investigated the possible protective effect of OLE on CP-induced kidney injury in rats, focusing on oxidative stress, inflammation, apoptosis and Nrf2/ARE/HO-1 signaling. Rats received 100 or 200 mg/kg body weight OLE for 15 days and a single injection of 150 mg/kg CP at day 16. CP induced kidney injury evidenced by the significantly increased serum creatinine and urea, and histopathological alterations, including glomerular atrophy, interstitial hemorrhage, dilated urinary space and necrosis. CP-induced rats exhibited increased kidney lipid peroxidation, protein carbonyl, nitric oxide (NO) and pro-inflammatory cytokines, and up-regulated NF-κB, Bax, cytochrome c and caspase-3. OLE ameliorated kidney function markers and prevented CP-induced tissue damage. In addition, OLE significantly prevented oxidative stress, inflammation and apoptosis by enhancing the antioxidant defenses and Bcl-2 expression, and suppressing the pro-inflammatory and pro-apoptotic markers NF-κB, Bax, cytochrome c and caspase-3. OLE up-regulated Nrf2, HO-1 and NQO-1 expression in the kidney of CP-induced rats. In conclusion, OLE has a substantial protective role against CP-induced nephrotoxicity in rats by up-regulating the Nrf2/ARE/HO-1 signaling, enhancing the antioxidant activity and attenuating inflammation and apoptosis. SN - 1950-6007 UR - https://www.unboundmedicine.com/medline/citation/30611992/Olea_europaea_leaf_extract_up_regulates_Nrf2/ARE/HO_1_signaling_and_attenuates_cyclophosphamide_induced_oxidative_stress_inflammation_and_apoptosis_in_rat_kidney_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0753-3322(18)37290-1 DB - PRIME DP - Unbound Medicine ER -