Is activation of lysosomal enzymes responsible for paracetamol-induced hepatotoxicity and nephrotoxicity?
Paracetamol overdose (300 mg kg(-1)) in mice resulted in a time-dependent increase in the liver weight; no change was seen for the kidney. The total acid phosphatase activities in the two tissues increased significantly 0.5 h after paracetamol overdose and remained elevated up to 3 h. Free as well as total cathepsin D activities increased significantly in both the tissues within 2-2.5 h of paracetamol treatment. Simultaneously tyrosine positive materials in the two tissues increased. RNAse II and DNAse II activities were low in liver and kidneys of the controls. Paracetamol treatment elevated both free and total RNAse II activity in the two tissues by 0.5 h. Maximum activity of DNAse II (free and total) was seen at 2.5 h after paracetamol administration. The results suggest that concerted action of cathepsin D, RNAse II and DNAse II may be responsible for paracetamol-induced hepatotoxicity and nephrotoxicity.
Khandkar
M A
MA
Department of Biochemistry, M.S. University of Baroda, India.
Parmar
D V
DV
Das
M
M
Katyare
S S
SS
D009597:4-Nitrophenylphosphatase / Q000378:metabolism; D000082:Acetaminophen / Q000633:toxicity*; D000596:Amino Acids / Q000378:metabolism; D018712:Analgesics, Non-Narcotic / Q000633:toxicity*; D000818:Animals; D002402:Cathepsin D / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology* / Q000378:metabolism; D003851:Deoxyribonucleases / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced / Q000201:enzymology* / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008247:Lysosomes / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D012260:Ribonucleases / Q000378:metabolism
D000596:Amino Acids; D018712:Analgesics, Non-Narcotic; D000082:Acetaminophen; D003851:Deoxyribonucleases; D012260:Ribonucleases; C020674:glycerol-2-phosphatase; D010744:Phosphoric Monoester Hydrolases; D009597:4-Nitrophenylphosphatase; D002402:Cathepsin D