Vitamin K protects against 7,12‐dimethylbenz(A)anthracene induced hepatotoxicity in Wistar rats

Abstract

Humans are daily exposed to 7,12‐dimethylbenz(a)anthracene (DMBA), a well known polycyclic aromatic hydrocarbons (PAH). This study investigated the role of dietary intake of Vitamin K (VK), a polyphenolic compound, with potential antioxidative properties, against DMBA‐induced hepatotoxicity. Sixty experimental animals (120‐150 g) were divided into six groups (A‐F): Control, DMBA (80 mg/kg bw) only, VK (0.00 g/10 kg) diet only, VK (7.5 g/10 kg) diet only, DMBA + VK (0.0 g/10 kg) diet and DMBA + VK (7.5 g/10 kg) diet. Single oral administration of DMBA (80 mg/kg body weight) to Wistar rats resulted in hepatic damage after 16 weeks. DMBA significantly (P < .05) decreased the activities of catalase (CAT), superoxide dismutase (SOD), glutathione‐S‐transferase (GST) and glutathione peroxidase (GPx). Levels of reduced glutathione (GSH) and Vitamin C were significantly decreased with increase in malondialdehyde (MDA) and nitric oxide (NO) levels in serum and liver. Aspartate aminotransaminase (AST), alanine aminotransaminase (ALT), γ‐glutamyltransferase (GGT), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) activities were significantly (P < .05) elevated in the serum but reduced in the liver of DMBA‐administered group. Ingestion of 7.5 g/10 kg VK diet prevented the up regulations in inflammatory biomarkers (granulocyte macrophage colony stimulating factor (GM‐CSF) and interleukin 17A (IL‐17A)) which elicited liver damaged in the DMBA‐treated group. DMBA induced hepatic alterations in DMBA‐treated group but was restored to near normal in VK (7.5 g/10 kg) diet group. These findings suggest the protective potential of increased dietary intake of vitamin K against DMBA‐induced hepatic dysfunction.

Transaminase Enzyme Activity and Histopathology Evaluation of Rat’s Liver Induced by DMBA with Temulawak Extract (Curcuma xanthorrhiza)

“…The AST enzyme activity values in the treatment group and DMBA group had values that were above the normal group values. This is due to the DMBA induction reported by Dosumu et al [25] can increase AST levels. Researchers [26] also reported that the AST enzyme will be more produced when breast tumor growth occurs.…”

“…These metabolites can then move to the mammary glands and form DNA adducts (DNA that binds to carcinogenic compounds). DMBA metabolism in the liver involves several stages involving phase I and II enzymes [25].…”

Rutin Suppresses DMBA Carcinogenesis in the Breast Through Modulating IL-6/NF-κB, SRC1/HSP90 and ER-α

“…Upregulation of iNOS expression produces NOs, which promote cancer formation and progression. 60,61 Rutin is a potent antioxidant polyphenol that reduces inducible nitric oxide synthase (iNOS) activity; attenuates mitochondrial damage; increases the glutathione (GSH)/GSSG ratio; enhances the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx); and modulates the production of pro-inflammatory cytokines by decreasing TNF-α and IL-1β generation in microglia. 35 Src kinase is activated by nitric oxide generation, but this activation could be abolished with a nitric oxide scavenger.…”

Dysbiosis in Patients with Chronic Kidney Disease: Let Us Talk About Vitamin K

“…Oxidative stress, resulting from the imbalance between the production of reactive oxygen species (ROS) and antioxidant activity, leads to macromolecular damage and subsequently chronic inflammation [48,49]. Both these features have deleterious effects on cell function, contributing to aging and the development of non-communicable chronic diseases, such as diabetes mellitus, hypertension, CVD, and CKD [4,50,51].…”

“…Studies (both in vitro and in vivo) have shown that vitamin K decreases the levels of IL-2, IL-6, IL-17A, IFN-γ, nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) expression through the inhibition of phosphor extracellular signal-regulated kinase (p-ERK) phosphorylation. This results in downregulation of NF-κB and p38 mitogen-activated protein kinase (MAPK) through the suppression of transcription factor AP-1, which leads to blocking of inflammatory pathways [50,57,60].…”