acid-phosphatase and diethyl-phthalate

Polychlorinated biphenyls (PCBs) are environmental pollutants known to act as xenoestrogens. PCBs and diethylphthalate (DEP) are ubiquitous environmental pollutants because both are used as plasticizers and in various other industrial applications. Therefore, a study was undertaken to evaluate the interactive toxicity of DEP and PCB in 21-day-old male and female pups of Wistar rats. Healthy young male and female albino rats of Wistar strain weighing 75-100g (6-7 weeks old) were randomly assigned to four groups of six each. Group I male and female rats were fed a normal diet and water ad libitum. Group II and III male and female rats were given PCB (Clophen A60) and DEP dissolved in corn oil mixed with the diet at 50 mg/kg of the diet (2.85 mg/kg body wt) individually to each group. Group IV male and female rats received a mixture of DEP and PCB (Clophen A60), each dissolved in corn oil mixed with the diet at 50 mg/kg of the diet (2.85 mg/kg body wt). Hundred days after the treatment, females were mated with males for 10 days. Exposure to DEP and PCB was continued throughout mating, gestation until termination at weaning, which was 150 days of total treatment period of adults. The pups from each group were then segregated on the basis of their sex. Six male and female pups each (approx. 21 days old) from each group were chosen randomly and were killed for toxicity study. Liver-to-body weight ratio showed significant increase in the male and female pups of PCB- and PCB+DEP-treated rats, whereas male pups of DEP alone treated rats showed significant increase and female pups showed significant decrease as compared to controls and other treated groups. Significant increase in liver and serum lactate dehydrogenase (LDH) and acid phosphatase (ACP) activity in the male and female pups of the three treated groups was observed. Alkaline phosphatase (ALP) activity was significantly increased only in the serum of male and female pups of the three treated groups, whereas significant decrease in the liver of male pups of the three treated groups. In the female pups, significant decrease in liver ALP was observed only PCB- and PCB+DEP-treated groups. Histology of liver showed severe vacuolation and steatosis in the hepatocytes of PCB-treated male and female pups and in PCB+DEP-treated group, vacuolation, and steatosis was much more predominant as compared to the PCB and DEP alone treated groups. DEP alone treated groups, both male and female pups showed mild vacuolation

Topics: Acid Phosphatase; Alkaline Phosphatase; Animals; Drug Synergism; Drug Therapy, Combination; Environmental Exposure; Environmental Pollutants; Fatty Liver; Female; L-Lactate Dehydrogenase; Liver; Male; Organ Size; Phthalic Acids; Polychlorinated Biphenyls; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Wistar; Reproduction; Toxicity Tests

Diethyl phthalate (DEP) is widely used in personal care products, plastics and medical devices at various concentrations, but its information is limited on its toxicity associated with exposure at high as well as low doses for a prolonged period. Therefore, a study was undertaken to understand the dose-response toxic effect of DEP in male Wistar rats. Control rats were fed on normal diet and water ad libitum. Rats were given DEP dissolved individually in corn oil mixed with the diet at 10, 25 and 50 mg/kg of the diet/day, which is equal to 0.57, 1.425 and 2.85 mg/kg body wt/day. After 5 months of treatment animals were sacrificed, enzymes and other biochemical parameters in the serum and liver were assessed. Liver weight to body weight ratio showed a significant increase only in 10 ppm DEP treated rats. A significant increase was observed in the serum ACP, LDH, ALT enzyme levels of 10 mg/kg treated rats as compared to control, 25 and 50 mg/kg treated rats. Other biochemical parameters like glycogen, total cholesterol, total triglycerides and lipid peroxidation were also increased in the liver of all the three treated groups. In the 10 and 50 mg/kg diet/day treated rats, there was a significant decrease in liver total GSH as compared to controls and 25 mg/kg treated rats. Histology of liver showed severe vacuolations, fatty degeneration and loss of hepatic architecture in the 10mg/kg treated rats, whereas in the 25 and 50 mg/kg treated rats only loss of hepatic architecture and granular deposits in the hepatocytes was predominant. Histology of liver by electron micrographs showed a significant dose-dependent proliferation of mitochondria in the hepatocytes, while the 10mg/kg treated rats showed increased number of peroxisomes in the hepatocytes. It is evident from this study that treatment with higher concentrations of DEP results in mitochondrial proliferation as well as accumulation of glycogen, cholesterol and triglycerides within the liver, but exposure to lower concentrations for longer periods results in increase in peroxisome numbers leading to severe hepatocellular changes which can be confirmed by significantly increased liver weights, elevated enzyme levels in the serum and liver and impaired metabolism of glycogen, cholesterol and triglyceride as well as altered liver histology.

Topics: Acid Phosphatase; Administration, Oral; Alanine Transaminase; Animals; Cholesterol; Dose-Response Relationship, Drug; Environmental Pollutants; Glycogen; Lipid Peroxidation; Liver; Male; Mitochondria, Liver; Organ Size; Phthalic Acids; Rats; Rats, Wistar; Toxicity Tests, Chronic; Triglycerides