Effects of total parenteral nutrition on drug metabolism gene expression in mice
ACTA PHARMACEUTICA SINICA B
Authors: Ferrucci-Da Silva, Christina; Zhan, Le; Shen, Jianliang; Kong, Bo; Campbell, Michael J.; Memon, Naureen; Hegyi, Thomas; Lu, Lucy; Guo, Grace L.
Abstract
Parenteral nutrition-associated liver disease (PNALD) is a liver dysfunction caused by various risk factors presented in patients receiving total parenteral nutrition (TPN). Omega-6 rich Intralipid (R) and omega-3 rich Omegaven (R) are two intravenous lipid emulsions used in TPN. TPN could affect the hepatic expression of genes in anti-oxidative stress, but it's unknown whether TPN affects genes in drug metabolism. In this study, either Intralipid (R) - or Omegaven (R)-based TPN was administered to mice and the expression of a cohort of genes involved in anti-oxidative stress or drug metabolism was analyzed, glutathione (GSH) levels were measured, and protein levels for two key drug metabolism genes were determined. Overall, the expression of most genes was downregulated by Intralipid (R)-based TPN (Gstp1, Gstm1, 3, 6, Nqo1, Ho-1, Mt-1, Gclc, Gclm, Cyp2d9, 2f2, 2b10, and 3a11). Omegaven (R) showed similar results as Intralipid (R) except for preserving the expression of Gstm1 and Cyp3a11, and increasing Ho-1. Total GSH levels were decreased by Intralipid (R), but increased by Omegaven (R). CYP3A11 protein levels were increased by Omegaven (R). In conclusion, TPN reduced the expression of many genes involved in anti-oxidative stress and drug metabolism in mice. However, Omegaven (R) preserved expression of Cyp3a11, suggesting another beneficial effect of Omegaven (R) in protecting liver functions. (C) 2020 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.
Glutathione S-Transferase Theta 1/Mu 1 Null Genotype and Risk of Development of Actinic Keratosis in Pakistani Population
JCPSP-JOURNAL OF THE COLLEGE OF PHYSICIANS AND SURGEONS PAKISTAN
Authors: Bajwa, Muhammad Imran; Rahim, Amena; Afzal, Muhammad; Mahmood, Amna
Abstract
Objective: To assess the frequency and association of Glutathione S-Transferase Theta 1 and Glutathione S-Transferase Mu 1 null genotypes in development of actinic keratosis (AK) in a group of Pakistani population. Study Design: Case-control analytical study. Place and Duration of Study: Department of Biochemistry, Islamic International Medical College, Rawalpindi in collaboration with Department of Dermatology, Railway Hospital and Rural Health Center, District Health Office, Rawalpindi from September 2018 to September 2019. Methodology: A total of 86 participants were included in this study with 27 biopsy proven cases of AK and 59 matched controls. Blood samples were collected after obtaining written informed consent; and DNA was extracted by Chelex (TM) method. Multiplex PCR (M-PCR) was done to find respective allelic frequencies of GSTM1 and GSTT1 genes in both cases and controls. Results: Mean age of participants in cases and controls was 62.93 +/- 10.29 years and was 61.42 +/- 9.96 years, respectively. There were 18 males (66.7%) and 9 females (33.3%); and 43 males (72.9%) and 16 females (27.1%) in cases and controls, respectively. There was a significant association of GSTT1 null genotype with AK (OR: 2.72, 95% CI: 1.05-7.05, p = 0.037). There was a positive correlation between GSTT1 null genotype and AK (r = 0.225, p = 0.037). Conclusion: GSTT1 null genotype has a significant association for AK development in the studied Pakistani population.