Effects of fructose-induced hypertriglyceridemia on hepatorenal toxicity of acetaminophen in rats

Diabetes and hypertriglyceridemia modify the mode of acetaminophen-induced hepatotoxicity and nephrotoxicity in rats and mice

“…They also suggested that the involvement of high-dose sucrose is at a step(s) occurring after the metabolic activation of APAP and that fructose has a primary role in the sucrose enhancement of APAP-toxicity in rats. This contradiction with the abovementioned results reported by Ishida et al (1995) (reduction of APAP hpatotoxicity by fructose) may be due to differences in treatment regimens between those two studies. In the study conducted by Hojo et al (2000), rats received a single oral administration of extremely high doses of sucrose (1.8 to 3.4 g/kg) concomitant with oral APAP.…”

“…In contrast, as mentioned later, fructose-induced hypertriglyceridemic rats showed only an increase in plasma triglyceride level, and they are considered to be of great benefit in the examination of the effects of hypertriglyceridemia on the mode of toxicity of various chemicals including APAP (Ishida et al, 1995).…”

“…Diabetes is associated with hyperlipidemia, an elevation of triglyceride and cholesterol levels that is one of the primary causes of a majority of diabetic complications (Saad and Naijar, 2005). Hypertriglyceridemic rats showed enhanced APAP-induced nephrotoxicity (Ishida et al, 1995) and a greater sensitivity to the nephrotoxic effect of cyclosporine A (Bohdancecká et al, 1999), suggesting that diabetes might have similar effects. Diabetes is also associated with increased blood glucose which leads to systemic oxidative stress in diabetes (Hunt and Wolff, 1991).…”

“…The contrast in triglyceride production between fructose and glulipogenic substrates available in the liver (Herzberg and Rogerson, 1982;Spence and Pitot, 1982). Neither hyperglycemia nor hyperinsulimemia can account for changes in APAP-toxicity in diabetic animal models since both fructose and glucose pretreatments produce both conditions (Kazumi et al, 1986), but only fructose pretreatment produces hypertriglyceridemia and changes in APAP-toxicity (Ishida et al, 1995). -cient in preventing hypoxic and APAP-induced damage to hepatocytes, and that its protective effect was related to its ability to provide glycolytic ATP (Annundi and DeGroot, 1989; Mourelle et al, 1991).…”

“…In the study conducted by Hojo et al (2000), rats received a single oral administration of extremely high doses of sucrose (1.8 to 3.4 g/kg) concomitant with oral APAP. In contrast, rats received a single ip injection of APAP after 3 or 5 weeks of pretreatment with fructose in drinking water ad libitum in the studies reported by Ishida et al (1995Ishida et al ( , 1997a. Ishida et al (1997d) also reported that renal APAPconcentrations during the early phase (15 and 30 min fructose-pretreated rats than those in normal ones and plasma and hepatic APAP concentrations in fructose-pretreated rats were greater than those in normal ones only at the later phase (plasma: 6 hr; liver: 6 and 12 hr after APAP-administration).…”