title: Low Plasma Zinc Is Associated with Higher Mitochondrial Oxidative Stress and Faster Liver Fibrosis Development in the Miami Adult Studies in HIV Cohort.
abstract: Background:Oxidative stress and reduced antioxidants may be a trigger for liver fibrogenesis. Reducing oxidative stress through higher antioxidant concentration may be a potential antifibrotic target.Objective:We aimed to investigate longitudinally whether plasma zinc, an antioxidant, is related to mitochondrial oxidative stress and the progression of liver fibrosis in the Miami Adult Studies in HIV (MASH) cohort.Methods:A prospective observational cohort study was conducted in 487 predominantly African American HIV-monoinfected and HIV/hepatitis C virus (HCV)-coinfected adults with a mean ± SD age of 47.08 ± 7.67 y from the MASH cohort and followed for a median of 34 mo. Blood was collected for plasma zinc and measures were used to calculate the fibrosis-4 (FIB-4) score (aspartate amino transferase, alanine aminotransferase, and platelets). Plasma zinc deficiency was defined as <0.75 mg/L. Total DNA was extracted from peripheral blood mononuclear cells and mitochondrial DNA (mtDNA) 8-hydroxyguanosine (8-oxo-dG) was determined. Adjusted mixed models were used to assess the relations between zinc, stage of liver disease, and oxidative stress over time and compared between HIV and HIV/HCV groups.Results:Zinc concentrations (β: -0.368, SE = 0.172;P= 0.033) and deficiency were associated with lower FIB-4 scores over time (β: 0.381, SE = 0.118;P= 0.001). Compared with those who were not zinc deficient, zinc-deficient participants had an increased risk of having more-progressed liver disease (OR: 1.91; 95% CI: 1.15, 3.16;P= 0.012). Higher mtDNA 8-oxo-dG was associated with zinc deficiency (β: 0.049, SE = 0.024;P= 0.044) and higher FIB-4 scores over time (β: 0.597, SE = 0.168,P< 0.001).Conclusions:Lower plasma zinc concentrations were associated with liver fibrosis progression and mitochondrial oxidative stress in the HIV and HIV/HCV groups. Zinc may play a role in the impact of liver disease outcomes.
authors.affiliation: Robert Stempel College of Public Health and Social Work, Florida International University, Miami, FL.
authors.forename: Sabrina S
authors.initials: SS
authors.lastname: Martinez
authors.affiliation: Robert Stempel College of Public Health and Social Work, Florida International University, Miami, FL.
authors.forename: Adriana
authors.initials: A
authors.lastname: Campa
authors.affiliation: Robert Stempel College of Public Health and Social Work, Florida International University, Miami, FL.
authors.forename: Yinghui
authors.initials: Y
authors.lastname: Li
authors.affiliation: Louis A Johnson Veterans Affairs Medical Center, Clarksburg, WV.
authors.forename: Christina
authors.initials: C
authors.lastname: Fleetwood
authors.affiliation: Center for Nanoscience and Technology, University of Notre Dame, Notre Dame, IN; and.
authors.forename: Tiffanie
authors.initials: T
authors.lastname: Stewart
authors.affiliation: Department of Nutrition and Kinesiology, University of Central Missouri, Warrensburg, MO.
authors.forename: Venkataraghavan
authors.initials: V
authors.lastname: Ramamoorthy
authors.affiliation: Robert Stempel College of Public Health and Social Work, Florida International University, Miami, FL; baumm@fiu.edu.
authors.forename: Marianna K
authors.initials: MK
authors.lastname: Baum
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D015331:Cohort Studies; D003677:Deficiency Diseases / Q000097:blood / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D005260:Female; D005431:Florida / Q000453:epidemiology; D015658:HIV Infections / Q000097:blood / Q000150:complications*; D006526:Hepatitis C / Q000097:blood / Q000150:complications*; D006801:Humans; D008103:Liver Cirrhosis / Q000209:etiology*; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology*; D015032:Zinc / Q000097:blood*
chemical_list: D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D015032:Zinc
keywords: HIV; HIV/HCV coinfection; mtDNA 8-oxo-dG; oxidative stress; zinc