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Naringin protects against cyclophosphamide-induced hepatotoxicity and nephrotoxicity through modulation of oxidative stress, inflammation, apoptosis, autophagy, and DNA damage.
Environ Sci Pollut Res Int. 2018 Jul; 25(21):20968-20984.ES

Abstract

Cyclophosphamide (CP) is a common chemotherapeutic agent that is effective against a wide variety of tumors. The associated hepatotoxicity and nephrotoxicity, however, limit its therapeutic use. Naringin (NG) is a natural flavanone glycoside that has pharmacological and therapeutic activities, such as anti-inflammation, anti-apoptotic, and antioxidant properties. Therefore, the present study was undertaken to evaluate the protective effect of NG against CP-induced hepatotoxicity and nephrotoxicity in rats. Rats were pre-treated with NG (50 and 100 mg/kg b.w.) for 7 days before administering a single dose of CP (200 mg/kg b.w.) on the seventh day. CP-induced hepatotoxicity and nephrotoxicity were associated with an increase in serum toxicity markers and a decrease in antioxidant enzyme activities. CP also induced inflammatory responses by increasing the levels of tumor necrosis factor-α (TNF-α), nuclear factor kappa B (NF-κB), interleukin-6 (IL-6), and interleukin-1β (IL-1β), and activities of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Moreover, it activated the apoptotic and autophagic pathway by increasing cysteine aspartate-specific protease-3 (caspase-3) expression and light chain 3B (LC3B) level and also increased the expression of 8-hydroxy-2'-deoxyguanosine (8-OHdG), which is the marker of oxidative DNA damage. Pre-treatment with NG (50 and 100 mg/kg), however, significantly decreased serum toxicity markers, increased antioxidant enzyme activities, and regulated inflammation, apoptosis, autophagy, and oxidative DNA damage in hepatic and renal tissues. These results indicated that NG was an effective protectant against CP-induced hepatotoxicity and nephrotoxicity.

Authors+Show Affiliations

Department of Biochemistry, Faculty of Veterinary Medicine, Bingol University, Bingol, Turkey.Department of Solhan School of Health Services, Bingol University, Bingol, Turkey.Department of Biochemistry, Faculty of Veterinary Medicine, Ataturk University, 25240, Erzurum, Turkey. fkandemir03@gmail.com.Department of Pathology, Faculty of Veterinary Medicine, Ataturk University, Erzurum, Turkey.Department of Biochemistry, Faculty of Veterinary Medicine, Ataturk University, 25240, Erzurum, Turkey.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29766429

Citation

Caglayan, Cuneyt, et al. "Naringin Protects Against Cyclophosphamide-induced Hepatotoxicity and Nephrotoxicity Through Modulation of Oxidative Stress, Inflammation, Apoptosis, Autophagy, and DNA Damage." Environmental Science and Pollution Research International, vol. 25, no. 21, 2018, pp. 20968-20984.
Caglayan C, Temel Y, Kandemir FM, et al. Naringin protects against cyclophosphamide-induced hepatotoxicity and nephrotoxicity through modulation of oxidative stress, inflammation, apoptosis, autophagy, and DNA damage. Environ Sci Pollut Res Int. 2018;25(21):20968-20984.
Caglayan, C., Temel, Y., Kandemir, F. M., Yildirim, S., & Kucukler, S. (2018). Naringin protects against cyclophosphamide-induced hepatotoxicity and nephrotoxicity through modulation of oxidative stress, inflammation, apoptosis, autophagy, and DNA damage. Environmental Science and Pollution Research International, 25(21), 20968-20984. https://doi.org/10.1007/s11356-018-2242-5
Caglayan C, et al. Naringin Protects Against Cyclophosphamide-induced Hepatotoxicity and Nephrotoxicity Through Modulation of Oxidative Stress, Inflammation, Apoptosis, Autophagy, and DNA Damage. Environ Sci Pollut Res Int. 2018;25(21):20968-20984. PubMed PMID: 29766429.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Naringin protects against cyclophosphamide-induced hepatotoxicity and nephrotoxicity through modulation of oxidative stress, inflammation, apoptosis, autophagy, and DNA damage. AU - Caglayan,Cuneyt, AU - Temel,Yusuf, AU - Kandemir,Fatih Mehmet, AU - Yildirim,Serkan, AU - Kucukler,Sefa, Y1 - 2018/05/15/ PY - 2017/11/06/received PY - 2018/05/06/accepted PY - 2018/5/17/pubmed PY - 2019/3/23/medline PY - 2018/5/17/entrez KW - Apoptosis KW - Autophagy KW - Cyclophosphamide KW - Hepatotoxicity KW - Inflammation KW - Naringin KW - Nephrotoxicity SP - 20968 EP - 20984 JF - Environmental science and pollution research international JO - Environ Sci Pollut Res Int VL - 25 IS - 21 N2 - Cyclophosphamide (CP) is a common chemotherapeutic agent that is effective against a wide variety of tumors. The associated hepatotoxicity and nephrotoxicity, however, limit its therapeutic use. Naringin (NG) is a natural flavanone glycoside that has pharmacological and therapeutic activities, such as anti-inflammation, anti-apoptotic, and antioxidant properties. Therefore, the present study was undertaken to evaluate the protective effect of NG against CP-induced hepatotoxicity and nephrotoxicity in rats. Rats were pre-treated with NG (50 and 100 mg/kg b.w.) for 7 days before administering a single dose of CP (200 mg/kg b.w.) on the seventh day. CP-induced hepatotoxicity and nephrotoxicity were associated with an increase in serum toxicity markers and a decrease in antioxidant enzyme activities. CP also induced inflammatory responses by increasing the levels of tumor necrosis factor-α (TNF-α), nuclear factor kappa B (NF-κB), interleukin-6 (IL-6), and interleukin-1β (IL-1β), and activities of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Moreover, it activated the apoptotic and autophagic pathway by increasing cysteine aspartate-specific protease-3 (caspase-3) expression and light chain 3B (LC3B) level and also increased the expression of 8-hydroxy-2'-deoxyguanosine (8-OHdG), which is the marker of oxidative DNA damage. Pre-treatment with NG (50 and 100 mg/kg), however, significantly decreased serum toxicity markers, increased antioxidant enzyme activities, and regulated inflammation, apoptosis, autophagy, and oxidative DNA damage in hepatic and renal tissues. These results indicated that NG was an effective protectant against CP-induced hepatotoxicity and nephrotoxicity. SN - 1614-7499 UR - https://www.unboundmedicine.com/medline/citation/29766429/Naringin_protects_against_cyclophosphamide_induced_hepatotoxicity_and_nephrotoxicity_through_modulation_of_oxidative_stress_inflammation_apoptosis_autophagy_and_DNA_damage_ L2 - https://dx.doi.org/10.1007/s11356-018-2242-5 DB - PRIME DP - Unbound Medicine ER -