Meral Öncü

Nephrotoxicity in rats induced by chlorpryfos-ethyl and ameliorating effects of antioxidantsy

Nephrotoxicity induced by chlorpyrifos-ethyl (CE) and ameliorating effects of melatonin and vitamin E plus vitamin C were evaluated in rats exposed to CE. Experimental groups were as follows: control (C), CE treated (CE), vitamin E plus vitamin C treated (Vit), melatonin treated (Mel), vitamin E plus vitamin C plus CE treated (Vit+CE), and melatonin plus CE treated (Mel+CE). The rats in the CE, Vit+CE and Mel+CE groups were administered orally with CE in two equal doses of 41 mg/kg body weight (0.25 LD50). Melatonin and vitamins E and C were administrated intramuscularly at the doses of 10, 150 and 200 mg/kg, respectively. The levels of thiobarbituric acid reactive substance (TBARS) and antioxidant potential (AOP), and the activities of glutathione peroxidase (GSHPx), catalase (CAT) and superoxide dismutase (SOD) were studied in the homogenates of kidney tissue. There were no significant differences in the activities of SOD and CAT between the experimental groups. The level of TBARS increased significantly (P<0.05) while AOP decreased significantly (P<0.05) in the CE group compared with the C group. GSH-Px activity was significantly (P<0.05) lower in the CE group and higher in the melatonin group than the control group. Histopathological changes were found in the kidney tissue of rats treated with CE. These were infiltration in mononuclear cells at perivascular and peritubular areas, hydropic degenerations in tubule epithelium and glomerular sclerosis. The severity of the lesions was reduced by administration of vitamins and melatonin. These results suggest that CE increases lipid peroxidation and decreases AOP by increasing oxidative stress, and that high doses of melatonin and a combination of vitamin E plus vitamin C considerably reduce the toxic effect of CE on kidney tissue of rats.

Protective role of melatonin and a combination of vitamin C and vitamin E on lung toxicity induced by chlorpyrifos-ethyl in rats.

The ameliorating effects of melatonin and vitamin C plus vitamin E were examined histologically and biochemically in lung tissues in rats exposed to chlorpyriphos-ethyl (CE). Experimental groups were as follows: Control group (C), CE treated group (CE), vitamin C plus vitamin E treated group (Vit), melatonin treated group (Mel), vitamin C plus vitamin E plus CE treated group (Vit + CE), and melatonin plus CE treated group (Mel + CE). Vitamin E and vitamin C were administered intramuscularly at the rates of 150 and 200 mg per kg body weight, respectively, in Vit and Vit + CE groups, once a day for 6 consecutive days. Melatonin was administered intramuscularly at the rate of 10 mg per kg body weight in Mel and Mel + CE groups, once a day for 6 consecutive days. At the end of the fifth day, the rats of CE, Vit + CE and Mel + CE groups were treated orally with CE dissolved in corn oil with two equal doses of 41 mg CE per kg body weight at zero and twenty-first hours. Tissue samples of lungs were taken by using appropriate techniques for biochemical and histological examinations under anesthesia at the twenty-fourth hours of CE administration, at the end of the sixth day of the experiment. In tissue homogenates, the level of thiobarbituric acid reactive substances (TBARS), antioxidant potential (AOP), and the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) were determined. TBARS was significantly high (p < 0.05) in CE group compared to control group, while TBARS was found to significantly decrease (p < 0.05) with Vit and Mel groups compared to control. On the other hand, TBARS was seen to significantly decrease (p < 0.05) in both groups of Vit + CE and Mel + CE compared to CE group. In comparison with CE group, SOD activity was significantly high (p < 0.05) with the groups of Vit, Mel, Vit + CE and Mel + CE. GSH-Px activity was found to significantly decrease (p < 0.05) with CE group, compared with both C and Vit groups. AOP was significantly lower (p < 0.01) in CE group than C group. Although there was an increased AOP with Vit + CE and Mel + CE groups compared to CE group, the increase in AOP was only seen to be significant (p < 0.05) in Mel + CE group. In comparison with C group, AOP significantly (p < 0.05) increased with Vit group. There was also a significant (p < 0.05) increase in AOP with Mel + CE group, compared with CE group. Additionally, AOP was significantly lower (p < 0.05) in Vit + CE group than Mel + CE group. Lungs were examined histologically at the end of sixth day. There were remarkable changes in the histomorphology of peribronchial and perivascular area in the lung of rats treated with CE. These were infiltration of mononuclear cells (such as lymphocytes, plasmocytes, macrophages), hyperplasia of type II pneumocyte, and thickened and increased connective tissue. Damage to the lung tissue such as increased inflammatory mononuclear cells in peribronchial and perivascular areas were more pronounced for the CE group than Vit + CE and Mel + CE groups in which these changes were higher than C, Vit and Mel groups. These results suggest that CE increases lipid peroxidation and decreases antioxidant enzymes activities and AOP due to increasing oxidative stress induced by CE, and high doses of vitamin C plus vitamin E and melatonin considerably reduce CE toxicity in lung tissues of rats.

Investigation of biochemical and histopathological effects of Mentha piperita L. and Mentha spicata L. on kidney tissue in rats

Peppermint plants have been used as a herbal medicine for many conditions, including loss of appetite, common cold, bronchitis, sinusitis, fever, nausea, vomiting and indigestion. This study is aimed at investigating the biochemical and histological effects of Mentha piperita L., growing in the Yenisar Bademli town of Isparta City, and Mentha spicata L., growing on the Anamas high plateau of Isparta City, on rat kidney tissue. Forty-eight male Wistar albino rats weighing 200 / 250 g were used for this study. Animals were divided into four experimental groups, each with 12 rats, as follows: control group (group I); 20 g/L M. piperita tea (group II); 20 g/L M. spicata tea (group III); 40 g/L M. spicata tea (group IV). The control group rats were given commercial drinking water (Hayat DANONESA water). The tea for the other groups was prepared daily and provided at all times to the rats during 30 days as drinking water. Plasma urea and creatinine levels were determined, and the levels of thiobarbituric acid reactive substance (TBARS) and the activities of glutathione peroxidase (GSH-Px), catalase (CAT) and superoxide dismutase (SOD) were studied in the homogenates of kidney tissue. The levels of plasma urea and creatinine were increased significantly (P B-0.0033) in groups III and IV when compared with group I. The activities of SOD and GSHPx were decreased significantly (P B-0.0033) in group IV when compared with group I. The activities of CAT were decreased significantly in groups III and IV (P B-0.033,P B-0.0033, respectively) when compared with group I. TBARS levels were increased significantly (P B-0.0033) in groups III and IV when compared with group I. In groups II, III and IV, hydropic degeneration of tubular epithelial cells, the epithelial cells with picnotic nuclei and eosinophilic cytoplasm, tubular dilatation and enlargements in Bowman capsules were observed histologically. However, in group II histopathological changes were more slight than in groups III and IV. In group IV, in addition to these changes, extremely hydropic degeneration of tubular epithelial cells, some atrophic tubules and glomerules, and focal mononuclear cell infiltrations in the kidney tissues of the rats were observed. In conclusion, the results indicate that M. piperita does not show nephrotoxicity but M. spicata presents markedly nephrotoxic changes in rats.

Effect of chronic fluorosis on lipid peroxidation and histology of lung tissues in first and second generation rats

This experiment was designed to investigate the lipid peroxidation and histological effects of chronic fluorosis on first- and second-generation rat kidney tissues. Sixteen virgin female Wistar rats were mated with eight males (2∶1) for approx 12 h to obtain first-generation rats. Mating was confirmed by the presence of sperm in vaginal smears. Sperm in vaginal smears was observed in 10 of 16 rats (d 0). These rats were identified as pregnant and included in this experiment. Pregnant rats were divided into two experimental groups (control and fluoride-supplemented), each containing five rats. The pregnant rats in the fluoride-supplemented group were exposed to 30 mg/L sodium fluoride (NaF) in commercial drinking water containing 0.07 mg/L NaF throughout the gestation and the lactation periods. After the lactation period, young animals (first generation [F1]) were exposed to the same amount of NaF in drinking water for 4 mo. At the end of the 4-mo experimental period, nine randomly chosen male rats (F1) were sacrificed, and the kidneys were removed for the histological and lipid peroxidation examinations. The remaining eight female rats were mated with four males (2∶1) for approx 12 h to obtain second-generation rats. Six female were identified as pregnant, and treated similarly throughout the gestation and the lactation periods. After the lactation period, the young male rats (second-generation male rats [F2]) were also treated similarly for 4 mo. At the end of the 4-mo experimental period, nine randomly chosen male rats (F2) were sacrificed, and the kidneys were removed for the histological and lipid peroxidation examinations. The rats in the control groups underwent the same procedure without NaF supplementation. It was found that the plasma fluoride and kidney TBARS levels of fluoride-supplemented F1 and F2 rats were higher than controls. Hydropic epithelial cell degenerations and moderate tubular dilatation were observed in some proximal and distal tubules. There were markedly focal mononuclear cell infiltrations and hemorrhage at some areas of the interstitium, especially at the corticomedullar junction. Mononuclear cell infiltrations were also evident in some peritubular and perivascular areas. Most of the vascular structures were congestive. Many Bowman capsules were narrowed. The severe degenerative changes in most of the shrunken glomerules and vascular congestion were also observed. It is concluded that chronic fluorosis causes a marked destruction in kidney tissues of F1 and F2 rats by causing lipid peroxidation.

Effects of pentoxifylline on amikacin-induced nephrotoxicity in rats.

The nephrotoxicity of amikacin (AK) was prevented with pentoxifylline (PTX) in a rat model. Rats were received a single injection of AK (1.2 g/kg, i.p.) with or without PTX pretreatment (25 mg/kg, orally). Renal morphology was investigated by light microscopy. Tissue samples and trunk blood were also obtained to determine renal malondialdehyde (MDA), blood urea nitrogen (BUN), and creatinine (Cr) levels. MDA production was found to be higher in AK group. PTX administration caused a significant decrease in MDA production. Morphological damage in rats given AK was severe in the kidney, whereas in rats given AK plus PTX, no histological changes occurred. It is concluded that PTX could be useful for reducing the nephrotoxic effects of AK.

Effect of Diclofenac Sodium Administration during Pregnancy in the Postnatal Period

Objective: The present study aimed to investigate the possible postnatal effects on the liver, kidney and testicular tissues of the offspring of rats given diclofenac sodium (DS) during pregnancy. Methods: At the beginning of the experiment, 80 rats (20 males and 60 females) were raised together for mating purposes. At the end, 50 pregnant rats were obtained and used as the experimental subjects. All pregnant rats were divided into 2 groups, each with 25 rats. The rats of the control group received physiological serum, 1 cm3/kg live weight per day, and the rats of the treatment group were injected with DS, 1 mg/kg live weight per day from the 5th to the 20th day of pregnancy. Four weeks after birth, tissue samples were obtained under anesthesia by perfusion fixation from a total of 40 offspring, 20 (10 males, 10 females) from the control group and 20 (10 males 10 females) from the DS group. Paraffin sections were dyed with hematoxylin eosin and examined under light microscopy. Results: The gestation period was significantly prolonged with DS-treated rats (p < 0.001). A moderate significant enlargement in the periportal area (p < 0.05), sinusoidal dilatation (p < 0.001), bile duct proliferation (p < 0.001), pyknosis in the nucleus of hepatocytes, and vacuolar degeneration in parenchymal cells (p < 0.001) were observed in DS-treated rats. Morphological changes in the liver were found to be similar both in female and male rats. Under light microscopy a similar morphological structure was observed in the kidney and testicular tissues of both the DS-treated and control rats. Conclusion: Significant morphological changes were observed in the livers of the offspring whose parents had been treated with DS. No significant differences were observed in liver morphology between the female and male offspring. There were no significant effects of DS on the morphology of the kidney and testis in all offspring.

Effects of misoprostol on cisplatin-induced renal damage in rats

Cisplatin (CP) is a potent anticancer drug. However, it has side effects on kidney such as nephrotoxicity. Abnormal production of reactive oxygen species (ROS) has been accused in the etiology of CP-induced nephrotoxicity. Several ROS scavengers have been reported to prevent nephrotoxicity after CP administration. In this study, we used prostaglandin E1 (PGE1) analogues misoprostol (MP) to reduce this damage. MP has gained considerable interest as a ROS scavenger. Rats were received a single injection of CP (5 mg/kg, i.p.) with or without MP pretreatment (200 mcg/kg, orally). The renal tissue morphology was investigated by light microscopy. Trunk blood was also obtained to determine lipid peroxidation product malondialdehyde (MDA) and activity of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT). CP administration increased MDA production and decreased SOD and CAT levels in the kidney tissue when compared to the control group. Morphological damage in CP administrated rats was also severe in the kidney tissue. MP treatment after CP application protected the renal tissues from CPs side effect. These findings indicate that MP has beneficial effects on CP induced nephrotoxicity in rats.

Investigation on the Histopathological Effects of Thyroidectomy on the Seminiferous Tubules of Immature and Adult Rats

Introduction: This study aimed to investigate the histopathological effects of thyroidectomy on both immature and adult rat testes. Materials and Methods: Male albino Wistar rats, 4 weeks old and weighing between 45 and 55 g, were used for this study. The experimental groups were as follows: 2-week control group (group I); 2-week thyroidectomy group (group II); 4-week control group (group III); 4-week thyroidectomy group (group IV); 6-week control group (group V), and 6-week thyroidectomy group (group VI). The control groups included both sham-operated and untreated rats. In groups II, IV and VI, total thyroidectomy was performed under ether anesthesia in all rats at 4 weeks of age. The rats were killed in the 2nd, 4th and 6th weeks, respectively, following the thyroidectomy. The testes of each animal were evaluated histologically. Results: In group II, spermatogenesis progressed to meiosis but round spermatids were found to be decreased and pachytene spermatocytes were observed to be increased when compared to group I. Giant pachytene spermatocytes were seen. There were also many degenerated cells of intermediate origin in the seminiferous epithelium. In groups IV and VI, spermatogonia and primary spermatocytes were normal in appearance, but there was widespread degeneration of the other spermatogenic cells. In addition, some closed lumina covered by degenerated and dead cells were observed. In group II, the mean outer diameter, luminal diameter and area occupied by seminiferous epithelium decreased by 19.74, 32.18, and 28.12%, respectively. In group IV, these data decreased by 23.9, 16.52, and 48.5%, respectively, and in group VI, by 21.10, 19.76 and 40.29%, respectively, when compared with the control groups. These data were statistically significant (p < 0.001). Conclusions: Thyroid hormones could have a marked influence on the seminiferous tubules of both immature and adult rats, and their permanent lack results in a depression in seminiferous tubule growth as shown by the reduced outer and luminal diameters and area occupied by the seminiferous epithelium, which could give rise to degenerative changes in the spermatogenic cells of thyroidectomized rats. In addition, all these changes could also result from both the inability of Sertoli cells to support spermatogenic cells and the diminished levels of GH and FSH.

Effect of thyroidectomy on the histology of rat sublingual gland

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.

Effects of Aspirin and Nimesulide on tissue damage in diabetic rats

This study was designed to compare the effect of Aspirin (AS) and Nimesulide (NM) on renal failure and vascular disorder in streptozotocin (STZ)-induced diabetic rats. Rats were divided into four groups; control, diabetic rats, diabetic rats plus AS and diabetic rats plus NM, which are COX inhibitors. The renal and aorta tissues morphology were investigated by light microscopy. Trunk blood was also obtained to determine plasma lipid peroxidation product malondialdehyde (MDA) and plasma activity of antioxidant enzymes. MDA levels were increased in the diabetic rats when compared to the control group. AS and NM administration caused a significant decrease in MDA production. Morphological damage in diabetic rats was severe in the kidney and in the aorta tissue. Treatment of AS reduced these damages, but NM did not exert positive effect on these damages in diabetic rats. As a result, although both AS and NM corrected lipid peroxidation parameters such as MDA via their antioxidant properties, only AS ameliorated pathological alteration in tissues. These findings indicate that there may be another mechanism in beneficial effect of AS in diabetic rats.