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New insights into the protection of growth hormone in cisplatin-induced nephrotoxicity: The impact of IGF-1 on the Keap1-Nrf2/HO-1 signaling.
Life Sci. 2020 Jul 15; 253:117581.LS

Abstract

AIMS

Cisplatin (CDDP) is an effective antineoplastic agent, however, its serious nephrotoxicity limits therapeutic use. Human growth hormone (hGH) has proved antioxidant and anti-inflammatory activities. The present study aimed to investigate the nephroprotective effects of hGH against CDDP-induced nephrotoxicity and the mechanisms underlying this nephroprotection.

MAIN METHODS

Male albino rats injected with CDDP (7 mg/kg) and nephrotoxicity indices, oxidative stress and inflammatory biomarkers (high mobility group box protein-1 (HMGB-1), soluble epoxide hydrolase (sEH), and nuclear factor-kappa B (NF-κB)) were assessed. Also, insulin-like growth factor-1 (IGF-1) and Nuclear factor-erythroid-2 (Nrf2)/heme oxygenase-1 (HO-1) pathway were assessed.

KEY FINDINGS

hGH (1 mg/kg) improved kidney function and antioxidant systems and showed intact renal tubular epithelium. Cisplatin upregulated the HMGB-1/NF-κB and downregulated Nrf2/HO-1 pathways which were reversed by hGH and aligned with increased renal IGF-1 expression. Also, IGF-1/sEH crosstalk might be involved in hGH nephroprotection. Moreover, hGH downregulated HSP70 and caspase-3 expressions.

SIGNIFICANCE

these results concluded that hGH can attenuate the inflammation and oxidative stress attained by CDDP probably through inhibition of Nrf2/HO-1 pathway. We also suggested that Keap1/Nrf2-mediated upregulation of the antioxidant HO-1 might inhibit HMGB-1/NF-κB signaling and thus provide the principal protection mechanism offered by hGH against CDDP-induced kidney injury.

Authors+Show Affiliations

Department of Pharmaceutical Sciences, Faculty of Pharmacy, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia; Department of Pharmacology & Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.. Electronic address: Jassie_81@hotmail.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32209424

Citation

Mahran, Yasmen F.. "New Insights Into the Protection of Growth Hormone in Cisplatin-induced Nephrotoxicity: the Impact of IGF-1 On the Keap1-Nrf2/HO-1 Signaling." Life Sciences, vol. 253, 2020, p. 117581.
Mahran YF. New insights into the protection of growth hormone in cisplatin-induced nephrotoxicity: The impact of IGF-1 on the Keap1-Nrf2/HO-1 signaling. Life Sci. 2020;253:117581.
Mahran, Y. F. (2020). New insights into the protection of growth hormone in cisplatin-induced nephrotoxicity: The impact of IGF-1 on the Keap1-Nrf2/HO-1 signaling. Life Sciences, 253, 117581. https://doi.org/10.1016/j.lfs.2020.117581
Mahran YF. New Insights Into the Protection of Growth Hormone in Cisplatin-induced Nephrotoxicity: the Impact of IGF-1 On the Keap1-Nrf2/HO-1 Signaling. Life Sci. 2020 Jul 15;253:117581. PubMed PMID: 32209424.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - New insights into the protection of growth hormone in cisplatin-induced nephrotoxicity: The impact of IGF-1 on the Keap1-Nrf2/HO-1 signaling. A1 - Mahran,Yasmen F, Y1 - 2020/03/21/ PY - 2020/02/16/received PY - 2020/03/17/revised PY - 2020/03/19/accepted PY - 2020/3/27/pubmed PY - 2020/6/17/medline PY - 2020/3/27/entrez KW - Cisplatin KW - Growth hormone KW - HMGB-1 KW - HO-1 KW - IGF-1 KW - Keap1 KW - Nephrotoxicity KW - Nrf2 SP - 117581 EP - 117581 JF - Life sciences JO - Life Sci VL - 253 N2 - AIMS: Cisplatin (CDDP) is an effective antineoplastic agent, however, its serious nephrotoxicity limits therapeutic use. Human growth hormone (hGH) has proved antioxidant and anti-inflammatory activities. The present study aimed to investigate the nephroprotective effects of hGH against CDDP-induced nephrotoxicity and the mechanisms underlying this nephroprotection. MAIN METHODS: Male albino rats injected with CDDP (7 mg/kg) and nephrotoxicity indices, oxidative stress and inflammatory biomarkers (high mobility group box protein-1 (HMGB-1), soluble epoxide hydrolase (sEH), and nuclear factor-kappa B (NF-κB)) were assessed. Also, insulin-like growth factor-1 (IGF-1) and Nuclear factor-erythroid-2 (Nrf2)/heme oxygenase-1 (HO-1) pathway were assessed. KEY FINDINGS: hGH (1 mg/kg) improved kidney function and antioxidant systems and showed intact renal tubular epithelium. Cisplatin upregulated the HMGB-1/NF-κB and downregulated Nrf2/HO-1 pathways which were reversed by hGH and aligned with increased renal IGF-1 expression. Also, IGF-1/sEH crosstalk might be involved in hGH nephroprotection. Moreover, hGH downregulated HSP70 and caspase-3 expressions. SIGNIFICANCE: these results concluded that hGH can attenuate the inflammation and oxidative stress attained by CDDP probably through inhibition of Nrf2/HO-1 pathway. We also suggested that Keap1/Nrf2-mediated upregulation of the antioxidant HO-1 might inhibit HMGB-1/NF-κB signaling and thus provide the principal protection mechanism offered by hGH against CDDP-induced kidney injury. SN - 1879-0631 UR - https://www.unboundmedicine.com/medline/citation/32209424/New_insights_into_the_protection_of_growth_hormone_in_cisplatin_induced_nephrotoxicity:_The_impact_of_IGF_1_on_the_Keap1_Nrf2/HO_1_signaling_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0024-3205(20)30329-5 DB - PRIME DP - Unbound Medicine ER -