The aim of this study was to compare the possible protective effects of N-acetylcysteine (NAC), caffeic acid (CAPE) and vitamin E (Vit-E) on doxorubicin-induced hepatotoxicity. Thirty-two male Wistar albino rats, weighing between 250 and 350 g were supplied and randomly divided into five groups. Animals in study groups were pretreated with a single dose of doxorubicin (Dox), which was administered intraperitoneally (i.p.). Control group (Group I) was treated with intraperitoneal saline injection. Group II did not received any antioxidant agent after the injection. Group III and Group IV were given CAPE and intraperitoneal vitamin E injection for eight days, respectively. Group V received NAC for eight days. The study was finished after 10 days. Tissue samples were collected from all animals and histopathological examination was performed. There was statistically significant difference between the experiment groups and controls by means of mononuclear cell infiltration and diameters of hepatic sinusoid, terminal hepatic venule (central vein) and portal area (portal canal). Changes related with hepatocellular damage were more prominent, whereas there was no significant difference between Dox and NAC given groups histopathologically. It was observed that structural changes were regressed after CAPE administration. However, this recovery was more prominent in vitamin E given group. These findings suggest that Dox induced liver damage could be efficiently reversed by vitamin E administration. It has been found that CAPE, but not NAC has protective effects on Dox-induced hepatocellular damage. Human & Experimental Toxicology (2007) 26, 519—525

The present study was conducted to investigate whether caffeic acid phenethyl ester (CAPE), an active component of propolis extract, has a protective effect on amphotericin B induced nephrotoxicity in rat models. Male Wistar-Albino rats were randomly divided into four groups: (I) control group (n = 10), (II) CAPE group (n = 9) which received 10 μmol/kg CAPE intraperitoneally (i.p.), (III) amphotericin B group (n = 7) which received one dose of 50 mg/kg amphotericin B, and (IV) amphotericin B plus CAPE group (n = 7) which received 10 μmol/kg CAPE i.p. and one dose of 50 mg/kg amphotericin B. The left kidney was evaluated histopathologically for nephrotoxicity. Levels of malondialdehyde (MDA), nitric oxide (NO), enzyme activities including catalase (CAT), and superoxide dismutase (SOD) were measured in the right kidney. Histopathological damage was prominent in the amphotericin B group compared to controls, and the severity of damage was lowered by CAPE administration. The activity of SOD, MDA, and NO levels increased and catalase activity decreased in the amphotericin B group compared to the control group (P = 0.0001, P = 0.003, P = 0.0001, and P = 0.0001, resp.). Amphotericin B plus CAPE treatment caused a significant decrease in MDA, NO levels, and SOD activity (P = 0.04, P = 0.02, and P = 0.0001, resp.) and caused an increase in CAT activity compared with amphotericin B treatment alone (P = 0.005). CAPE treatment seems to be an effective adjuvant agent for the prevention of amphotericin B nephrotoxicity in rat models.

To investigate prenatal and post-natal effects of extremely low frequency (ELF) electric field (EF) on growth and pubertal development, pregnant Wistar rats were randomly distributed among three groups. The pregnant rats of the prenatal group were exposed to 24-hour EF at 50 Hz EF 10 kV/min during pregnancy and their subsequent randomly selected female pups continued to be exposed until puberty. The post-natal group was unexposed to EF during pregnancy, but randomly selected female pups from this group were exposed to EF between delivery and puberty at the same doses and duration as the prenatal group. The third group was a sham-exposed group. The mean birth weight and weight gain of the pups during study period were found significantly reduced in prenatal group than post-natal and sham-exposed groups (p < 0.001). No difference could be found among the three groups for body weight at puberty (p > 0.05). The mean age at vaginal opening and estrous were significantly higher at prenatal group than post-natal and sham-exposed groups (p < 0.001). Serum insulin-like growth hormone-1 (IGF-1) levels were found significantly reduced in prenatal exposure group compared with the other two groups (p < 0.001). There was no difference for birth weight, weight gain, the mean age at vaginal opening and estrous and IGF-1 levels between post-natal and sham-exposed groups (p > 0.05). There was also no difference for FSH, LH and E2 levels at puberty among the three groups (p > 0.05). Histological examination revealed that both the prenatal and post-natal groups had the evidence of tissue damage on hypothalamus, pituitary gland and ovaries. In conclusion, early beginning of prenatal exposure of rats to 24 hours 50 Hz EF at 10 kV/m until puberty without magnetic field (MF) resulted in growth restriction, delayed puberty and reduced IGF-1 levels in female Wistar rats. These effects probably associated with direct toxic effects of EF on target organs. Post-natal exposure to EF at similar doses and duration seems to be less harmful on target organs. Post-natal exposure to EF at similar doses and duration seems to be less harmful.

This study was carried out to investigate the effect of thyroidectomy on the histology of rat sublingual gland. Twenty-eight male Wistar albino rats, aged 4 weeks and weighing between 45-55 g, were used. The rats were divided into two experimental groups (control and thyroidectomy), each containing 14 animals. Total thyroidectomy of rats was performed under ether anesthesia in thyroidectomy group. The rats in the control group were sham operated without having the thyroidectomy. Seven rats randomly selected from both groups were fixed using the perfusion fixation technique 2 and 6 weeks after thyroidectomy, and their sublingual glands were harvested for histological investigation. No histological difference was observed between the two groups 2 weeks after thyroidectomy. However, 6 weeks after thyroidectomy considerable cytoplasmic vacuolization of the epithelial cells of the mucous tubules was seen in the thyroidectomy group compared to the controls. Enlargement of mucous tubules was also observed, and the lumina in most of the tubules was quite dilated. In the stroma surrounding the parenchymal tissues, increased lipid tissue mass was observed. In addition, increased connective tissue mass and mononuclear cell infiltrations were evident. Furthermore, the number of mast cells was significantly higher in the thyroidectomy group than in the controls 6 weeks after thyroidectomy. It was concluded that the thyroid gland and hormones might have an influence on the histology of the sublingual gland.

The aim of this study was to investigate whether thiamine pyrophosphate (TPP) has biochemical and histological preventive effects on oxidative liver damage induced by paracetamol (APAP). Rats were divided into the following groups: healthy control (HG), APAP (AG, 1500 mg/kg, orally), thiamine pyrophosphate (TPPG, 100 mg/kg, intraperitoneally), APAP+NAC (ANAC, 100 mg/kg, intraperitoneally), APAP+TPP (ATPG) and APAP+NAC+TPP (ANTG). Oxidant, antioxidant parameters, liver function tests and histological assessment were performed between groups. Malondialdehyde levels in the AG, HG, TPPG, ANAC, ATPG and ANTG groups were 0.470 AE 0.210, 0.213 AE 0.004, 0.194 AE 0.001, 0.197 AE 0.06, 0.199 AE 0.008 and 0.173 AE 0.010 lmol/g protein, respectively. Total glutathione levels were 7.787 AE 0.395, 14.925 AE 0.932, 13.200 AE 0.984, 13.162 AE 0.486, 13.287 AE 0.787 and 13.500 AE 0.891 lM/g protein, respectively. In the AG group, marked liver damage occurred with the elevation of liver function tests and oxidative stress markers, such as malondialdehyde, myeloperoxidase and nitric oxide (p < 0.05). Biochemical results were congruent with the histological changes of oxidative damage. Compared to the AG group (p < 0.05), TPP significantly reduced oxidant parameter levels in the ATPG group and simultaneously increased the antioxidant parameter levels of catalase and glutathione. The histological changes were improved to almost normal hepatic structure. Moreover, TPP had nearly the same hepatoprotective effect as NAC, and there was statistically no additional benefit with NAC co-treatment. There was no statistically significant difference (p > 0.05) among the ANAC, ANTG and ATPG groups in terms of oxidant/ antioxidant levels. TPP proved to be as efficacious as standard therapy and may be beneficial in APAP-induced hepatotoxicity.Acetaminophen (Paracetamol, APAP) is widely used for its antipyretic and analgesic efficacy. APAP is safe and has few side effects when used at therapeutic levels. However, an overdose either in therapeutic contexts or in suicide can induce severe hepatotoxicity and acute liver failure [1,2]. Nearly 50% of all acute liver failure cases are due to APAP toxicity and carry 30% mortality [3]. In the United States, more than 100,000 cases of APAP intoxication occur annually [4]. Hepatotoxicity is the outcome of the reactive, toxic metabolite of APAP. If taken at recommended daily doses, nearly 85-90% of APAP is metabolized by glucuronidation and sulphation in the liver and subsequently excreted in the urine. In normal conditions, reactive metabolite N-acetyl-p-benzo-quinoneimine (NAPQI) is detoxified by endogenous glutathione (GSH). However, after APAP overdose, the GSH stores are depleted and sufficient NAPQI detoxification cannot be processed. This leads NAPQI to covalently bind to intracellular proteins [5]. Covalent binding is thought to be the progenitor mechanism of centrilobular hepatic necrosis, causing oxidative stress, lipid peroxidation and the depletion of protein thiols [6].In APAP hepatot...