[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to determine the effect of herbicide fluazifop, on the early occurring changes in rat liver regarded as hepatic markers of peroxisome proliferators (PPs). Fluazifop was administered orally to male Wistar rats at increasing doses from 5.6 to 891 mg/kg body weight per day for 1, 2, 4, 7 and 14 consecutive days and peroxisome proliferation, induction of some peroxisome-associated enzymes and mitogenesis (S-phase, M-phase and percentage of binucleated hepatocytes) were studied. Short-term treatment of rats with fluazifop resulted in hepatomegaly due to time dependent proliferation of smooth endoplasmic reticulum (SER) and peroxisomes. The increase in the number of peroxisomes in the hepatocytes was supported by an increase in peroxisomal palmitoyl-CoA oxidation and catalase activity. In contrast to other PPs fluazifop induced low rate of rcplicative DNA synthesis and did not affect mitoses (M-phase). DNA synthesis was accompanied by the appearance of binucleated hepatocytes. Thus, we can conclude that fluazifop produces in male Wistar rats hepatomegaly due to cellular hypertrophy. The threshold dose for palmitoyl-CoA oxidation and DNA synthesis was 112 and 223 mg/kg body weight per day, respectively. The value for hepatomegaly and catalase activity was 56 mg/kg body weight per day. The results presented in this paper demonstrated that fluazifop can be classified as a weak rodent PPs.
[Show abstract][Hide abstract] ABSTRACT: A study was performed to determine whether diclofop (2-(4-(2,4-dichlorophenoxy) phenoxy)propionic acid), introduced as a herbicide, exhibits the properties of peroxisome proliferators (PPs). Diclofop was administered orally at 7-56 mg/kg body weight per day to male Wistar rats for 2, 4, 7 or 14 consecutive days and some effects regarded as early hepatic markers of PPs were studied. The early changes in rat liver, produced by short-term treatment with diclofop consisted of mitogenesis and, time- and dose-related increase in liver weight. Hepatomegaly was typically associated with proliferation of smooth endoplasmic reticulum (SER) and peroxisomes. The parallel biochemical measurements showed that there was a dose-dependent increase in peroxisomal palmitoyl-CoA oxidation and catalase activity in treated rats. Markers of hepatocellular proliferation (S- and M-phase) indicated that mitogenesis was transient and declined despite continuation of diclofop treatment. The threshold exposure level for the palmitoyl-CoA oxidation (one of the peroxisome proliferation markers) was approximately the same (14 mg/kg body weightxper day) as for the stimulation of mitogenesis in Wistar rats. However, for hepatomegaly and catalase activity the threshold exposure level was 7 mg/kg body weightxper day. The results presented here demonstrate clearly that diclofop belongs to a class of rodent PPs.