IS ACTIVATION OF LYSOSOMAL-ENZYMES RESPONSIBLE FOR PARACETAMOL-INDUCED HEPATOTOXICITY AND NEPHROTOXICITY

Paracetamol overdose (300 mg kg(-1)) in mice resulted in a time-depend ent increase in the liver weight; no change was seen for the kidney. T he total acid phosphatase activities in the two tissues increased sign ificantly 0.5h after paracetamol overdose and remained elevated up to 3h. Free as well as total cathepsin D activities increased significant ly in both the tissues within 2-2.5 h of paracetamol treatment. Simult aneously tyrosine positive materials in the two tissues increased. RNA se II and DNAse II activities were low in liver and kidneys of the con trols. Paracetamol treatment elevated both free and total RNAse II act ivity 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 res ults suggest that concerted action of cathepsin D, RNAse II and DNAse II may be responsible for paracetamol-induced hepatotoxicity and nephr otoxicity.