The protective effect of Morin against ifosfamide-induced acute liver injury in rats associated with the inhibition of DNA damage and apoptosis

Özdemir S., Küçükler S., Çomaklı S., Kandemir F. M.

DRUG AND CHEMICAL TOXICOLOGY, cilt.45, sa.3, ss.1308-1317, 2022 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 45 Sayı: 3
  • Basım Tarihi: 2022
  • Doi Numarası: 10.1080/01480545.2020.1822390
  • Dergi Adı: DRUG AND CHEMICAL TOXICOLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, EMBASE, Environment Index, Food Science & Technology Abstracts, International Pharmaceutical Abstracts, MEDLINE, Veterinary Science Database
  • Sayfa Sayıları: ss.1308-1317
  • Anahtar Kelimeler: Ifosfamide, Morin, liver injury, oxidative stress, inflammation, apoptosis, NF-KAPPA-B, GENE-EXPRESSION, RISK-FACTORS, ENCEPHALOPATHY, HEPATOTOXICITY, INFLAMMATION, ACTIVATION, TOXICATION, PRODUCT, CANCER
  • Atatürk Üniversitesi Adresli: Evet

Özet

Morin is a flavonoid and broadly found in white berry and cranberry branch. Ifosfamide (IFOS) is known as an anticancer and cytotoxic drug especially on the liver. This study aimed to explore the potential protective effects of Morin against IFOS-induced liver toxicity in rats. The model group of rats received a single injection of IFOS (500 mg/kg; i.p.) at day 2, whereas the protective groups of rats were given two different doses of Morin (100 and 200 mg/kg; given by gavage) at days 1 and 2. All animals were then culled 24 h post-IFOS injection. We observed that IFOS caused liver injury, oxidative stress, inflammation, DNA damage, and apoptosis. However, Morin decreased the levels of aspartate aminotransferase (AST), alkaline phosphatase (ALP), alanine aminotransferase (ALT) (p < 0.05). While Morin contributed to the recovery of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione (GSH) levels, Morin decreased the levels of malondialdehyde (MDA) induced by IFOS in the liver (p < 0.05). Besides, the levels of nuclear factor kappa B (NF-kappa B), tumor necrosis factor-alpha (TNF-alpha), and P53 measured by ELISA test were reducedviaMorin administration (p < 0.05). Lastly, the mRNA transcript levels ofBax,Apaf-1,Bcl-2,Bcl-xL, and inducible nitric oxide synthase (iNOS) determined by RT-PCR were down-regulated in the Morin groups (p < 0.05). These results indicate that Morin plays a protective role by reducing oxidative stress, inflammation, and apoptosis in the IFOS-induced liver injury in rats.