Sub-lethal concentration of arsenic interferes with the proliferation of hepatocytes and induces in vivo apoptosis in Clarias batrachus L.
We studied the hepatocellular alterations induced by sub-lethal concentrations (0.50 muM) of arsenic in Indian catfish Clarias batrachus L. Sub-lethal arsenic exposure altered serum aspartate aminotransferase and alkaline phosphatase levels and brought about significant changes in different serum biochemical parameters. Arsenic exposure reduced total hepatocyte protein content and suppressed the proliferation of hepatocytes in a time-dependent manner. Routine histological studies on liver documented arsenic-induced changes characterized by dilated sinusoids, formation of intracellular edema, megalocytosis, vacuolation and appearance of hepatic cells with distorted nuclei. Transmission electron microscopy of hepatocytes further revealed hyperplasia and hypertrophy of mitochondria, development of dilated rough endoplasmic reticulum and changes in peroxisome size with duration of arsenic exposure. Degeneration of mitochondrial cristae and condensation of chromatin was also evident in arsenic-exposed hepatocytes. A significant number of hepatocytes isolated from arsenic-exposed fish stained with annexin V and demonstrated DNA ladder characteristic of apoptosis. Single-cell gel electrophoresis of exposed hepatocytes also revealed the development of comets usually seen in apoptotic cells. Using specific inhibitors it was determined that the arsenic-induced apoptosis of hepatocytes was caspase-mediated, involving the caspase 3 pathway.
Datta
Soma
S
Immunobiology Laboratory, School of Life Sciences, Visva-Bharati University, Santiniketan 731 235, India.
Saha
Dhira Rani
DR
Ghosh
Debabrata
D
Majumdar
Tanmay
T
Bhattacharya
Shelley
S
Mazumder
Shibnath
S
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017304:Annexin A5 / Q000032:analysis; D017209:Apoptosis / Q000187:drug effects*; D001151:Arsenic / Q000633:toxicity*; D001219:Aspartate Aminotransferases / Q000097:blood; D053148:Caspase 3 / Q000502:physiology; D002397:Catfishes; D049109:Cell Proliferation; D053938:DNA Fragmentation / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects* / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000648:ultrastructure
D017304:Annexin A5; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D053148:Caspase 3; D001151:Arsenic