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ALIPHATIC ALCOHOLS PROPAGATE OXIDATIVE STRESS‐RESPONSIVE CELL DEATH SIGNALS IN THE MOUSE LIVER AND KIDNEYS BY PERTURBING EXPRESSION OF PRO‐ AND ANTIAPOPTOTIC GENES
Author(s) -
Lawana Vivek,
Patel Ami,
Ray Sid D
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1050.11
Subject(s) - oxidative stress , apoptosis , programmed cell death , cyp2e1 , nephrotoxicity , chemistry , kidney , liver injury , glutathione , toxicity , pharmacology , alcohol , biochemistry , medicine , metabolism , cytochrome p450 , enzyme
Toxic effects of aliphatic alcohols [methanol (ME), ethanol (ET), isopropyl alcohol (ISO) and tertiary‐butanol (tBut)] remains an important focus of mechanistic investigations; however, their mechanisms of actions at the genetic level and relative potential to induce apoptotic and necrotic cell deaths remains unclear. The main study objectives were to compare: i) hepato‐ and nephrotoxic potentials, ii) abilities to produce oxidative stress (OS), and iii) impact on the expression of proapoptotic (bax, APAF‐1, Cyt c & caspase 3) and antiapoptotic (bcl‐2, bcl‐xL) genes in the liver and kidneys by various alcohols. A single LD40 dose of ME, ET, ISO & tBut were orally gavaged to 4 groups of female ICR mice (12–15 wks old). Control group received only water, and all animals were sacrificed at 24hrs. Blood was collected for serum chemistry and organs were collected (frozen at −70 °C) for westerns and tissue biochemistry. Compared to control (100%), several organ injury biomarkers considerably increased [serum ALT (388%); BUN (462%); liver MDA (215%); kidney MDA (206%)], whereas, reduced glutathione content significantly decreased in the liver (24%) and kidneys (39%) by t‐Butanol. Pro‐apoptogenic genes showed increased expression, whereas, antiapoptotic group showed a dramatic decrease. ME, ET and ISO also showed similar trends. These results suggest a clear‐cut mediation of various alcohol‐induced oxidative stress in inducing cell injury and cell death via cell death signaling pathways, and it was observed that higher the number of carbon atoms, the greater was the toxicity (tBut>ISO>ET>ME). Suppo. By AMS Coll of Pharm & HScs.